OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.

Objective To investigate the impact of sleep modes on the risk for diseases of the body systems.Methods Based on a subset of UK Biobank dataset comprising 87 617 participants,3 sleep dimensions including 6 sleep indicators were obtained through a wrist-worn accelerometer,that is sleep duration and onset,sleep rhythm(relative amplitude and stability),and sleep quality(sleep efficiency and number of awakenings).Latent profile analysis(LPA)was applied to identify and classify distinct sleep modes.Then their longitudinal medical records were the association between different sleep modes and the risk for 467 diseases.Results LPA identified 5 subgroups of unique sleep modes in the participants.Among the 5 subgroups,the subgroup 4 had relatively optimal levels in above sleep indicators.Compared to the subgroup 4,the other 4 subgroups exhibited variations in different sleep dimensions,with at least one indicator demonstrating an unfavorable trend.These subgroups also revealed differences in racial composition,shift work and social deprivation index.Moreover,there were notable differences in the risk of various system diseases among the subgroups(P<0.05).When compared to the subgroup 4,the other 4 subgroups exhibited an elevated risk for certain diseases(comprising a total of 126 diseases),with the diseases of the circulatory system,digestive system and musculoskeletal system most common.Among the 5 subgroups,the subgroup 2(shorter sleep duration and later sleep onset)and the subgroup 5(rhythm disorder)had the highest counts of associated risks,amounting to 85 and 91 types,respectively,but there was certain difference in their systematic composition.Conclusion There are different sleep modes within the participants,and the modes are potentially associated with an increased risk for diseases of body systems.Comprehensive interventions targeting overall sleep modes rather than single sleep indicator may yield obvious health benefits.

Objective:To investigate the safety of the tetravalent meningococcal conjugate vaccine (MPCV-ACYW) in combination with the inactivated poliomyelitis (IPV) vaccine and diphtheria-tetanus-acellular pertussis (DTaP) vaccine for infants aged 3-5 months and provide real-world evidence for the immunization strategy of vaccine combination.Methods:From June to October 2023, a total of 600 3-month-old infants were selected and divided into three groups: control group, mono-vaccination group and combined vaccination group. They were simultaneously or individually vaccinated with MPCV-ACYW, IPV and DTaP vaccines at 3, 4, and 5 months of age, respectively. The incidence rate of adverse reactions within 30 days after each dose was observed.Results:All 600 infants completed at least one vaccination and entered the safety data analysis. The age of the control group (100 infants), the mono-vaccination group (250 infants), and the combination group (250 infants) was (101.20±7.88), (102.26±7.94), and (102.35±7.76) days, respectively. The body lengths were (63.00±3.02), (62.55±3.06), and (63.14±4.02) cm, respectively. The body weights were (6.90±0.77), (6.86±0.94), and (6.99±0.95) kg, respectively. Boys accounted for 49%, 50.4%, and 52.4%, respectively, with no statistically significant differences (all P>0.05). The overall incidence rates of adverse reactions in the control group, mono-vaccination group, and combined vaccination group were 4.00%, 2.80%, and 3.20%, respectively, with systemic adverse reaction rates of 3.00%, 2.40%, and 2.00%. The incidence rates of local adverse reactions were 1.00%, 0.40%, and 1.20%, with no statistically significant differences (all P>0.05). Adverse reactions were mainly grade 1, with incidence rates of grade 1 adverse reactions of 3.00%, 2.00%, and 1.60% in the three groups, and incidence rates of grade 2 adverse reactions of 1.00%, 0.80%, and 1.60%, respectively. No grade 3 or 4 serious adverse reactions occurred, and the differences were not statistically significant (all P>0.05). The adverse reaction symptoms of the three groups were mainly systemic reactions, among which fever and diarrhea symptoms were reported in individual cases in each group, with no statistically significant differences in the incidence rate (all P>0.05). The symptoms of adverse reactions were mostly transient and self-relieved, all of which were cured. Conclusion:The combination of MPCV-ACYW and IPV or DTaP vaccines is safe for infants aged 3-5 months.

AIM:To investigate the role of S100 calcium-binding protein A8(S100A8)in a canine model of atrial fibrillation(AF)induced by obstructive sleep apnea(OSA).METHODS:Ten adult Beagle dogs were randomly as-signed to OSA(n=5)and control(n=5)groups.The OSA model was established by daily tracheal intubation with alternat-ing airway obstruction and ventilation recovery for 4 h per day,sustained over 12 weeks.Model validation was conducted through arterial blood gas analysis,airway pressure monitoring,and esophageal pressure measurements.Open-chest elec-trophysiological studies were performed to assess atrial effective refractory period(ERP),dispersion of ERP(dERP),and AF inducibility.Tandem mass tag-based quantitative proteomics was used to identify differentially expressed proteins in atrial tissue.Key protein expression and localization were verified using immunohistochemistry and immunofluorescence.RESULTS:Compared with the control group,the OSA group exhibited significantly lower arterial blood pH and partial pressure of oxygen,and higher partial pressure of carbon dioxide in arterial blood,confirming successful model establish-ment.Histopathological analysis revealed disorganized cardiomyocyte architecture,fatty degeneration,inflammatory cell infiltration,and a significant increase in myocardial fibrosis in the OSA group(P<0.05).Electrophysiological data showed increased AF inducibility and dERP,and decreased ERP(P<0.05).Proteomic analysis identified 267 differen-tially expressed proteins,including 128 up-regulated and 139 down-regulated proteins.Immunohistochemical analysis showed significant upregulation of S100A8,S100A9,myeloperoxidase,and nuclear factor-κB p65(P<0.05),while im-munofluorescence demonstrated increased expression of matrix metalloproteinase-9 and transforming growth factor-β1 in the OSA group(P<0.01).CONCLUSION:The OSA promotes upregulation of S100A8 in myocardial tissue,enhances atrial electrical remodeling and fibrosis,and increases susceptibility to AF.These findings suggest that S100A8 may play a key role in the pathogenesis and progression of OSA-related AF.

Objective:To examine the attentional processing of verbal emotional information in college students with subclinical depression.Methods:Fifty college students were recruited(24 with subclinical depression group and 26 in the control group)were recruited from a university in Liaoning Province to investigate the atten-tional bias of subclinically depressed college students towards verbal emotional information(experiment 1).In addi-tion,48 college students(20 with subclinical depression and 28 in the control group)were recruited to investigate the attention disengagement of subclinically depressed college students from verbal emotional information(experi-ment 2).In experiment 1,two groups passively viewed words and recorded the eye movement data of emotional words.In experiment 2,two groups were asked to watch the emotional word-neutral word pair.When color borders were presented around neutral words,the attention disengagement latency that was the time taken by the eye saccade from emotional words to neutral words was recorded.Results:The results of experiment 1 showed that the total fix-ation duration of negative words in the subclinical depression group was longer than that in the control group(P＜0.01).The results of experiment 2 showed that attention disengagement latency of negative words in the subclinical depression group was longer than that in the control group(P＜0.05).Conclusion:College students with subclini-cal depression exhibit attentional bias towards negative verbal information and difficulties in attentional disengage-ment.

Osteoarthritis is a chronic degenerative joint disorder that adversely affects the quality of life of patients.Its pathological characteristics mainly involve the degeneration,destruction,and functional loss of articular cartilage.As one of the most crucial structures in the joint,articular cartilage is an avascular tissue composed of extracellular matrix synthesized by sparsely distributed chondrocytes.Chondrocyte apoptosis is one of the programmed cell death modalities of chondrocytes.During the normal physiological process,the proliferation and apoptosis of chondrocytes maintain a dynamic equilibrium,jointly safeguarding the homeostasis of articular cartilage.However,in the osteoarthritis process,the stimulation of related cytokines after tissue damage induces an imbalance between chondrocyte proliferation and apoptosis,resulting in excessive chondrocyte apoptosis,and subsequently leading to the degradation and degeneration of cartilage.Clinically,traditional Chinese medicine and its related therapeutic approaches remain one of the principal means for treating osteoarthritis in China.The traditional Chinese medicine,which are bioactive compounds extracted from traditional herbal medicines,has gradually gained recognition thanks to their convenient to take and remarkable therapeutic effect.Therefore,this review takes the signaling pathways involved in the inhibition of chondrocyte apoptosis by traditional Chinese medicine as the entry point,systematically retrieves and screens and summarizes relevant studies at home and abroad in the past five years,and analyzes the mechanism of action of related signaling pathways in the treatment of chondrocyte apoptosis in osteoarthritis by traditional Chinese Medicine,providing new options for the pharmacological treatment of osteoarthritis.