Aim To explore the mechanism of Gano-derma lucidum polysaccharides(GLPS)promoting my-elin repair and regeneration in mice with chronic demy-elination induced by cuprizone(CPZ).Methods A total of 40 C57BL/6 mice were randomly divided into four groups:Normal+NS,Normal+GLPS,CPZ+NS and CPZ+GLPS.A chronic demyelination model was established using 0.2％CPZ.Open field and elevated plus maze tests were performed to observe the behavior-al changes in the mice.Immunofluorescence staining and Western blot were used to detect changes in myelin basic protein expression in the corpus callosum.ELISA was performed to measure the levels of TNF-α,IL-6,IL-1β and IL-10 in brain homogenates.Immunofluo-rescence staining was also used to observe the expres-sion of ionized calcium binding adapter molecule 1(Iba1)and neural-glial antigen 2(NG2).RT-qPCR and Western blot were conducted to assess the mRNA and protein expression levels of MBP,iNOS,COX-2,JAK2 and STAT3.Results Mice in the CPZ+NS group showed a significant decrease in body weight,cognitive behavior abnormalities,and impaired myelin regeneration.The expression of pro-inflammatory fac-tors increased,while anti-inflammatory factors de-creased.Additionally,Iba1 and NG2 expression in-creased,and the JAK2/STAT3 signaling pathway was activated.After GLPS intervention,the mouse body weight increased,myelin regeneration occurred,cogni-tive behavior was improved,the expression of inflamma-tory factors decreased,anti-inflammatory factors in-creased,NG2 expression was further elevated,and the proliferation of microglia as well as the activation of the JAK2/STAT3 signaling pathway was inhibited.Conclu-sions GLPS can improve cognitive behavior abnormali-ties and inflammatory responses in chronic demyelinated mice by inhibiting the JAK2/STAT3 signaling pathway,thereby promoting myelin repair and regeneration.

AIM To compare the effects of Shaoling Formula emulsion versus its decoction on epidermal barrier function in a psoriasis mouse model.METHODS The Shaoling Formula emulsion was prepared by emulsification,whereas the decoction was produced by aqueous extraction.A psoriasis-like mouse model was established by topical application of 5％imiquimod cream(50 mg).The mice were randomly assigned to normal control,model control,Shaoling Formula emulsion group(13.26 g/kg),Shaoling Formula decoction group(13.26 g/kg),blank emulsion group,and positive control group(calcipotriol betamethasone ointment group,2.5 g/kg).After treatment for six consecutive days,the mice had their severity of skin lesions assessed with psoriasis area and severity index(PASI)scoring.Upon the completion of the treatment,the mice had transepidermal water loss(TEWL)and stratum corneum hydration(SCH)determined by the GPSkin Barrier;their histopathological changes in skin lesions observed using HE staining;their levels of TNF-α,IL-6,IL-17A,IL-22,and IL-23 in lesions detected by ELISA;and their Aquaporin 3(AQP3)expression analyzed by Western blot.RESULTS Compared to the model group,both the Shaoling Formula emulsion and positive control group demonstrated significant reductions in PASI scores(P＜0.01)and increased SCH(P＜0.01);decreased serum levels of TNF-α,IL-6,IL-17A,IL-22 and IL-23(P＜0.05,P＜0.01);histopathological improvements including attenuated parakeratosis/hyperkeratosis,reduced acanthosis,diminished dermal inflammatory cell infiltration,and normalized vasodilation;and upregulated AQP3 expression(P＜0.05).The Shaoling Formula decoction group exhibited reduced PASI scores(P＜0.01);and increased SCH(P＜0.05);decreased levels of IL-6,IL-17A,IL-22 and IL-23 in skin lesions(P＜0.05,P＜0.01).Notably,the emulsion group exhibited higher AQP3 protein expression than the decoction group(P＜0.05).CONCLUSION Shaoling Formula emulsion outperforms its decoction in restoring epidermal barrier function in psoriatic mice.This superiority is mechanistically linked to enhanced AQP3 protein expression and improved SCH.

AIM To investigate the effect of Tongmai Kaiqiao Pills on angiogenesis and JAK2/STAT3/VEGF signaling pathway in rats with vascular cognitive impairment(VCI).METHODS Ten of seventy-two male SD rats were randomly selected as sham operation group,and the remaining rats were made VCI rat model by ligation of common carotid artery in stages.Rats after successful modeling were randomly divided into model group,low and high dose groups of Tongmai Kaiqiao Pills(13.8 g/kg,27.6 g/kg),nimodipine group(10 mg/kg)and high dose of Tongmai Kaiqiao Pills+AG490(JAK2 inhibitor)group(Tongmai Kaiqiao Pills 27.6 g/kg+AG490 3 mg/kg).The samples were taken after 4 weeks of corresponding dose of drugs.Pathological changes in hippocampus were observed by HE staining.Nissl staining was used to observe the loss of neurons in hippocampus.Western blot was used to detect the protein expressions of p-JAK2,p-STAT3 and VEGF in hippocampus.The ultrastructure of neurons in hippocampus was observed by transmission electron microscope.The expression of CD34 was detected by immunofluorescence staining and the microvessel density(MVD)of ischemic penumbra was calculated.RESULTS Compared with the sham operation group,the escape latency of the model group was prolonged(P＜0.01),and the times of crossing the platform were reduced(P＜0.01);neurons in hippocampus were loose in structure and disordered in arrangement;the number of Nissl bodies decreased and the loss was serious;mitochondrial crista dissolved and disappeared,and mitochondrial damage was aggravated;the protein expressions of p-JAK2,p-STAT3 and VEGF in hippocampus increased(P＜0.05);the number of MVD in hippocampus increased(P＜0.01).Compared with the model group,the escape latency of rats in each dose group of Tongmai Kaiqiao Pills and nimodipine group were shortened(P＜0.01),and the times of crossing the platform were increased(P＜0.01);the number of hippocampal neurons increased,the morphology was normal,and the disorder degree improved;Nissl's corpuscles were abundant and the loss is reduced;mitochondrial damage was reduced and gradually returned to normal shape;the protein expressions of p-JAK2,p-STAT3 and VEGF in hippocampus increased(P＜0.05,P＜0.01);the number of MVD in hippocampus increased(P＜0.05,P＜0.01).AG490 reversed the high-dose effect of Tongmai Kaiqiao Pills(P＜0.05,P＜0.01).CONCLUSION Tongmai Kaiqiao Pills may promote angiogenesis,reduce neuronal damage and promote the recovery of brain function by activating JAK2/STAT3/VEGF signaling pathway,thus playing an improving role in VCI rats.

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

This study was aimed at developing an in vitro fluorescent substrate assay for the activity of leucyl aminopeptid-ase(LAP)from Echinococcus multilocularis and comparing it with the chemical chromogenic substrate enzyme activity assay.Through the establishment of reaction conditions for the fluorescent substrate-based in vitro enzyme activity assay,we com-pared the differences between the fluorescent substrate L-Leucine-7-amido-4-methylocoumarin(Leu-AMC)and the chemical chromogenic substrate L-Leucine-4-nitroanilide(Leu-pNA)through molecular docking,inhibition rates,and precision measures.Molecular docking revealed that the fluorescent substrate Leu-AMC had higher affinity for the protein than the chemical chromogenic substrate Leu-pNA.Through analysis of the effects of varying reaction conditions on fluorescence intensi-ty,we optimized the fluorescent substrate enzyme activity assay to demonstrate favorable performance at a reaction temperature of 37℃,a pH of 9.0,a protein concentration of 800 nmol/L,and a reaction duration of 60 minutes.Leu-AMC exhibited significant and distinct responses at a 5 μmol/L substrate concentration,under varying substrate conditions.The fluo-rescent substrate assay demonstrated more significant intergroup differences than the chemical chromogenic substrate assay when various inhibitors were added.This study established a fluorescence-based enzyme activity assay for leucyl aminopeptidase from Echinococcus multilocularis by using Leu-AMC as the substrate;this method demonstrated a more significant intergroup difference and sensitivity than the chemical chromogenic substrate assay.

Aim To investigate the role of FRMD4A in autophagy of placental trophoblast cells in preeclampsia(PE).Methods The placental tissues and clinical data of normal pregnancy and PE were obtained,and the histopathological changes were observed by HE staining.An in vitro model of hypoxia-induced HTR-8/SVneo trophoblast cells was established.The expres-sions of LC3B Ⅱ/Ⅰ and p62 in placental tissues and hypoxic cell models were analyzed by Western blot.The expression of FRMD4A was detected by qRT-PCR,Western blot and immunofluorescence,and the correlation between the expression level of FRMD4A and the clinical characteristics of the subjects was ana-lyzed by Pearson correlation analysis.Hypoxia induced trophoblast cells were transfected with si-FRMD4A,and the expression of LC3 B Ⅱ/Ⅰ and p62 was analyzed by Western blot.Results Compared with the normal group,the expression of LC3B Ⅱ/Ⅰ in PE placental tissues and hypoxia-induced trophoblast models was significantly upregulated,while the expression of p62 was significantly downregulated.Meanwhile,the ex-pression of FRMD4A increased significantly.Moreo-ver,its expression was positively correlated with the maternal systolic blood pressure,diastolic blood pres-sure,and platelet count,but negatively correlated with the neonatal weight(P＜0.01).In addition,hypoxia-induced trophoblast cells transfected with si-FRMD4A showed a significant decrease in LC3B Ⅱ/Ⅰ and an increase in p62 expression.Conclusions The expres-sion of FRMD4A is upregulated in PE placenta and hy-poxia-induced trophoblast cell model.Interfering with it can significantly hinder the autophagy process of trophoblast cells,suggesting that it may serve as a po-tential molecular target to participate in the pathologi-cal process of PE.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective To explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson's disease(PD)through fecal microbiota transplantation.Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Fecal microbiota from both the model group and the curcumin(Cur)-treated group(80 m g/kg)were collected and analyzed.The experiment involving fecal microbiota transplantation was structured into four distinct groups,fecal microbiota solvent transplantation group(FMTcon),model fecal microbiota transplantation group(FMTmodel),MPTP-induced model group(model),and model group subjected to fecal microbiota transplantation following curcumin treatment(model+FMTCur).The motor skills of the mice were assessed by using rod rotation,pole climbing experiment,and open field tests.Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase(TH)-positive neurons in the substantia nigra of the brain.Additionally,the gene expression of tumor necrosis factor-α(TNF-α)in the midbrain of mice was analyzed,alongside the protein expression of nuclear factor-κB(NF-κB)and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3).Results The subacute PD animal model in mice was successfully established,and fecal microbiota were separated and gathered.The model group exhibited significant motor impairment,as evidenced by a shortened rod rotation time(P＜0.05),prolonged pole climbing time(P＜0.05),significantly reduced total movement distance within the open field(P＜0.001),and decreased time spent in the central zone(P＜0.01).The relative expression level of TH+neurons in the substantia nigra was significantly reduced(P＜0.01).Moreover,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with significant elevations in protein expression of NF-κB(P＜0.001),phosphorylated NF-κB(p-NF-κB)(P＜0.01),NLRP3(P＜0.001),and Caspase-1(P＜0.01).The transplanted model microbial group(FMTmodel)also exhibited motor impairment,manifested by a trend of shortened rod rotation time,prolonged pole climbing time,a significant decrease in total movement distance within the open field(P＜0.01),and a trend of shortened time spent in the central zone.The relative expression level of TH+neurons in the substantia nigra decreased significantly(P＜0.05).Additionally,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with notable elevations in the protein expression of NF-κB(P＜0.05),and Caspase-1(P＜0.01).Treatment with curcumin in the fecal microbiota transplantation group of mice(model+FMTCur)showed improvements in motor abilities,evidenced by shortened pole climbing time(P＜0.05),significantly prolonged rod rotation time(P＜0.01),and extended time spent in the central zone(P＜0.05).The relative expression level of TH+dopaminergic neurons in the substantia nigra increased significantly(P＜0.05).Moreover,mRNA expression of TNF-α in the midbrain decreased significantly(P＜0.01),along with notable reductions in the protein expression of NF-κB(P＜0.001),p-NF-κB(P＜0.01),NLRP3(P＜0.05),and Caspase-1(P＜0.01).Conclusion Fecal microbiota transplantation in PD model mice can induce behavioral deficits,damage TH+neurons in the substantia nigra,and trigger neuroinflammation in the brain.Subsequent curcumin treatment can ameliorate these deficits,reverse damage to TH+neurons,reduce neuroinflammatory factors,and decrease the expression of NF-κB and NLRP3 pathways.This preliminary evidence suggests that curcumin may improve Parkinsonian behavioral deficits in mice by modulating the gut microbiota.

Objective This study aimed to provide an effective scientific basis for prevention and control of cockroaches on aircrafts by identifying cockroach-carried pathogens,and assess the insecticidal efficacy of gel bait mediated cockroach control on aircrafts,to provide technical guidance for aircraft disinsection.Methods Cassette-trapping was used to trap cockroaches,and the carried pathogens were detected using bacterial cultivation techniques.The gel bait mediated killing rate was calculated after 1,7,and 30 d by field application of gel bait.Results A total of 411 cockroaches were captured,and all were identified as Blattella germanica.26 strains of pathogenic bacteria were isolated from the trapped cockroaches.The killing rates of cockroaches were 58.8％-96.3％with 1-30 day application of gel bait.Statistically significant differences were observed in cockroach killing rates on different days(χ2=58.95,P<0.01).Conclusions B.germanica carry a large variety of pathogenic bacteria and opportunistic pathogens and are thus important infectious disease carriers.Gel bait agents have proven to be very effective against cockroaches on aircrafts.

Objective To investigate the population composition,seasonal dynamics,and infestation levels of cockroaches in Lanzhou,China,and to provide information for the scientific development of cockroach control strategies.Methods Monitoring was conducted at three locations using the sticky trap method.Habitats included farm product markets,catering establishments,hotels,hospitals,and residential areas.Results From 2016 to 2023,the average cockroach density was 0.77 insects per board,with an average infestation rate of 10.84%.Blattella germanica was the dominant species.Seasonal density of cockroaches showed an approximately unimodal distribution,peaking in September.The highest average density and infestation rates were observed in farm product markets.Conclusions Cockroach density and infestation levels in Lanzhou remained relatively low.A comprehensive prevention and control strategy focusing on environmental management in key areas should be implemented according to the seasonal fluctuations.