Atherosclerosis(AS)is an inflammatory cardiovascular disease characterized by plaque accumulation in the arterial wall,leading to increased morbidity and mortality of related cardiovascular disorders.The main pathological mechanisms of AS include lipid deposition,oxidative stress,and chronic inflammation,with disease progression involving endothelial cell dysfunction,macrophage polarization,foam cell formation,and smooth muscle cell proliferation or apoptosis.Mitochondria are essential organelles that provide energy for cellular metabolism,and the mitochondrial quality control(MQC)system is the fundamental mechanism maintaining mitochondrial functional homeostasis.MQC dysfunction can induce vascular phenotype changes through pathways such as oxidative stress,apoptosis,and inflammation,thereby promoting the progression of AS.Therefore,targeting MQC to regulate mitochondrial function may become a new direction for the treatment of AS.This review summarizes the molecular mechanisms of MQC,including mitochondrial biogenesis,mitochondrial dynamics,and mitochondrial autophagy(mitophagy),and further elucidates the role of abnormal MQC in the pathological processes of AS,aiming to provide a scientific basis for identifying potential targets to delay the progression of AS and developing related drugs.

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.

AIM To study the chemical constituents from the stems and barks of Maytenus variabilis(Hemsl.)C.Y.Cheng.METHODS The 95％ethanol extract from the stems and barks of M.variabilis was isolated and purified by silica gel,Sephadex LH-20 and semi preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-three compounds were isolated and identified as β-amyrin(1),3β-acetoxyolean-12-en-11-one(2),ursa-12-ene-11-one-3-ol octocosate(3),friedelin(4),canophyllol(5),pinoresinol(6),medioresinol(7),isolariciresinol(8),dihydrodehydrodiconiferyl alcohol(9),vanillic acid(10),7R,8S-5-methoxydihydrodehydroconiferyl alcohol(11),β-hydroxypropiovanillone(12),triptregeline B(13),triptregeline E(14),(+)-evofolin B(15),2,5-dimethoxybenzoquinone(16),olean-12-ene-3,11-dione(17),β-sitosterol(18),(-)-(7R,7'R,7"S,8S,8'S,8"S)-4',4"-dihydroxy-3,3',3",5-tetramethoxy-7,9',7',9-diepoxy-4,8"-oxy-8,8'-sesquineolignan-7",9"-diol(19),phyllostadimer B(20),rayalinol(21),lyoniresinol(22),dihydrobuddlenol B(23).CONCLUSION Compounds 3,9-11,13-14,16,19-21,23 are isolated from genus Maytenus for the first time,and compounds 2,4-5,7-8,12,15,17,22 are first found from this plant.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Pancreatic cancer is a highly malignant tumor,and its incidence rate has been slowly increasing since 2000.Although the improvement of diagnosis and treatment has led to an increase in the five-year survival rate of pancreatic cancer compared to 50 years ago,it remains one of the discouraging tumor diseases regarding its prognosis.In 2024,many achievements were made in the research of early screening,disease mechanism,clinical diagnosis and treatment of pancreatic cancer,showing a good prospect for clinical application.In early screening,artificial intelligence(AI)technology has empowered early diagnosis and screening of pancreatic cancer,pushing clinical diagnosis and treatment to a new level.Additionally,improvements in the accuracy of technologies such as liquid biopsy have provided new directions for early screening of pancreatic cancer.In terms of research on disease pathogenesis,3D genome mapping technology has revealed the polyclonal origin and genetic heterogeneity of pancreatic intraepithelial neoplasm(PanIN).In basic research,a branched organ simulation system that mimics the unique structural characteristics of pancreatic cancer provides a new model for in vitro studies of pancreatic cancer.Lactate,an important tumor metabolite,links the metabolic microenvironment of pancreatic cancer with epigenetic changes,revealing potential therapeutic targets.Defects in the histone H3K36 trimethyltransferase SETD2 contribute to endogenous epigenetic dysregulation in pancreatic cancer and promote mitochondrial oxidative phosphorylation(OXPHOS)and tumor progression.The platelet-derived growth factor receptor(PDGFR)axis,which facilitates communication between stromal cells and cancer cells,forms a bidirectional secretory circuit and may become a new therapeutic target.Chimeric antigen receptor macrophage(CAR-M)therapy targeting the tyrosine kinase receptor c-MET demonstrates potential for synergistic enhancement with chemotherapy drugs.Macrophages in the pancreatic cancer microenvironment promote the development of pancreatic cancer cachexia through the CCL5/TRAF6/nuclear factor-κB(NF-κB)pathway,suggesting that macrophages could be an effective target for predicting and intervening in the development of pancreatic cancer cachexia.In terms of advancements in diagnosis and treatment,surgery following neoadjuvant chemotherapy can improve overall survival(OS)in resectable and borderline resectable patients,but further optimization of neoadjuvant chemotherapy protocols is needed.The first clinically effective KRASG12D-targeted drug has been reported,and research on inhibitors of a wide range of KRAS mutants is continually emerging.Patient stratification based on glycolysis-related scores(GRS)can further guide the selection of treatment protocols."Intelligent exosomes"(ExoSmart)enhance cellular uptake capacity to assist in improving chemotherapy efficacy.The implementation of clinical trials combining immunotherapy with chemotherapy is expected to synergistically improve the efficacy of pancreatic cancer treatment.Pembrolizumab and anlotinib combined with albumin-bound paclitaxel/gemcitabine(PAAG)have shown great efficacy and safety in first-line treatment of metastatic pancreatic cancer(mPC)patients.The cancer vaccine ELI-002 2P,which targets KRAS mutation-encoded neoantigens,can induce an antitumor immune response.Oncolytic adenovirus therapy can synergistically improve the efficacy of treatment in advanced pancreatic ductal adenocarcinoma patients when combined with chemotherapy.This article reviewed the latest major progress in the field of basic research and diagnosis and treatment of pancreatic cancer in 2024.

Aim To explore the protective effect of the isochroman compound Asperisochroman B(AB)on oxygen-glucose deprivation/reoxygenation(OGD/R)injury of neurons based on the PI3K/AKT/Foxo1 path-way and to reveal the related mechanism.Methods Primary neurons were cultured and the OGD/R model was constructed.The primary neurons were divided in-to the blank control group,OGD/R group,and AB low,medium,and high concentration(3,10,30 μmol·L-1)groups.The effects of AB on primary neurons were determined by CCK-8 assay,lactate dehydrogen-ase(LDH)release assay,and Hoechst 33342 stai-ning.The expression levels of PI3K,AKT,and Foxo1-related proteins were detected by Western blot.After intervention with the PI3K inhibitor(LY294002)and re-modeling and intervention with high concentra-tion of AB(30 μmol·L-1),the expression of PI3K/Foxo1 pathway-related proteins was detected by West-ern blot.Results Compared with the OGD/R group,AB could significantly increase the cell survival rate of primary neurons and reduce the release of LDH.The results of Hoechst 33342 and immunofluorescence stai-ning showed that AB reduced apoptosis after OGD/R injury.Western blot results showed that compared with the OGD/R group,after AB intervention,the expres-sion levels of Bcl-2 and NeuN proteins in neurons sig-nificantly increased(P＜0.01),and the expression level of Bax protein significantly decreased(P＜0.01).At the same time,it upregulated the expres-sion levels of p-AKT and PI3K proteins,promoted Foxo1 phosphorylation,and downregulated the expres-sion of Foxo1.Compared with the high-dose AB group,LY294002 could inhibit the changes of the a-bove indicators and reverse the protective effect of AB on OGD/R-injured primary neurons.Conclusions AB can alleviate oxygen-glucose deprivation/reoxygen-ation-induced neuronal injury,and its mechanism may be related to the activation of the PI3K/AKT/Foxo1 signaling pathway.

OBJECTIVES: To investigate the chain mediating role of family care and emotional management in the relationship between social support and anxiety among rural primary school students. METHODS: A questionnaire survey was conducted among students in grades 4 to 6 from four counties in Hunan Province. Data were collected using the Social Support Rating Scale, Family Care Index Scale, Emotional Intelligence Scale, and Generalized Anxiety Disorder -7. Logistic regression analysis was used to explore the influencing factors of anxiety symptoms. Mediation analysis was conducted to assess the chain mediating effects of family care and emotional management between social support and anxiety. RESULTS: A total of 4 141 questionnaires were distributed, with 3 874 valid responses (effective response rate: 93.55%). The prevalence rate of anxiety symptoms among these students was 9.32% (95%CI: 8.40%-10.23%). Significant differences were observed in the prevalence rates of anxiety symptoms among groups with different levels of social support, family functioning, and emotional management ability (P<0.05). The total indirect effect of social support on anxiety symptoms via family care and emotional management was significant (β=-0.137, 95%CI: -0.167 to -0.109), and the direct effect of social support on anxiety symptoms remained significant (P<0.05). Family care and emotional management served as significant chain mediators in the relationship between social support and anxiety symptoms (β=-0.025,95%CI:-0.032 to -0.018), accounting for 14.5% of the total effect. CONCLUSIONS Social support can directly affect anxiety symptoms among rural primary school students and can also indirectly influence anxiety symptoms through the chain mediating effects of family care and emotional management. These findings provide scientific evidence for the prevention of anxiety in primary school students from multiple perspectives.
Humans ; Female ; Male ; Social Support ; Anxiety/etiology* ; Child ; Students/psychology* ; Emotions ; Logistic Models

OBJECTIVE: To study the results, re-donation situation and characteristics of single-reagent reactive blood donors who were put into the reentry strategy in Wuhan area, explore the rationality and effectiveness of the current reentry strategy, and provide data support for the improvement of the reentry process of blood donors. METHODS: From January 2020 to December 2023, blood donors who conform the reentry criteria and voluntarily applied for returning to Wuhan Blood Center were tested and the results were analyzed. According to the reentry strategy, serological testing and nucleic acid testing were carried out in parallel, serological testing was performed by ELISA with reagents from two different manufacturers, and the primary reactive samples were tested by double-well retest, and HBV/HCV/HIV nucleic acid detection was performed by RT-PCR with an individual donor test mode. Supplementary HBcAb testing was applied for HBV single reagent reactivity by chemiluminescence method. Supplementary TP-WB testing was applied for returning blood donors with repeated TP single reagent reactivity. If returning blood donors with HIV single reagent reactivity were repeated single reagent reactivity, the samples were sent to local CDC for confirmatory test. RESULTS: 7 098 blood donors were qualified for reentry, 716 donors voluntarily applied for reentry, 436 donors successfully reentry, 251 donors entered the next round, 29 donors could not reentry. The reentry rates for the past four years were 66.67%（42/63）, 54.73%（81/148）, 60.71%（136/224） and 62.99%（177/281）, respectively. Up to December 31, 2023, 275 donors donated blood again, and the donation rates for past four years were 76.19%（32/42）, 72.84%（59/81）, 61.76%（84/136） and 56.50%（100/177）, respectively. After donating blood, 31 donors were disqualified again by blood screening and subjected to permanent deferral. The results of returning to the team had statistical differences in reentry items, educational level, age, and marriage（P < 0.05）. CONCLUSION The current reentry strategy adopted by the blood donation and supply institution can effectively retain part of blood donors, reduce the negative emotions of blood donors and increase blood resources.
Humans ; Blood Donors ; China ; Hepatitis B ; Enzyme-Linked Immunosorbent Assay ; Hepatitis C ; Male

OBJECTIVE: To investigate the pattern of hepatitis B virus (HBV) infection and the prevalence of hepatitis D virus (HDV) infection among voluntary blood donors who tested reactive for HBV in Wuhan, and to provide data support for the prevention and treatment of HBV and HDV infections. METHODS: Electrochemiluminescence (ECL) method was used to detect hepatitis B serological markers in the samples with HBsAg and/or HBV DNA reactivity, and the HBV infection in different groups was statistically analyzed. The HDV IgM and IgG antibodies were screened by ELISA, and the prevalence of HDV infection in the retained samples was analyzed. RESULTS: In 351 ELISA and/or nucleic acid test (NAT) reactive samples, the serological tests for hepatitis B revealed that 4 cases (1.1%) were positive for HBsAg, HBeAg, and anti-HBc, 182 cases (51.9%) were positive for HBsAg, anti-HBe, and anti-HBc, and 55 cases (15.7%) were negative for HBsAg but positive for anti-HBc. Among them, the HBsAg ELISA dual reagent reactive group (HBsAg R&R group) and the HBsAg ELISA single reagent reactive/HBV DNA reactive group (HBsAg R&NR/HBV DNA R group) had the highest rates of HBsAg(+), anti-HBe(+), and anti-HBc(+), accounting for more than 90% and 65%, respectively, followed by low activity of HBV acute infection or chronic carriers, accounting for about 5% and 20%, respectively. In the HBsAg R&NR/HBV DNA NR group, the combined proportion of individuals with anti-HBs single positive and all hepatitis B serological markers negative accounted for 78%, and those who were HBsAg negative but anti-HBc positive accounted for approximately 20%. In the HBsAg NR&NR/HBV DNA R group, there was nearly 9% of HBsAg(+), anti-HBe(+), and anti-HBc(+), the remaining were all HBsAg negative but anti-HBc positive, with a 100% anti-HBc positivity rate in this group. No HDV IgM or IgG antibodies were detected in the retained samples. CONCLUSION Blood donors with HBV-reactive results in blood screening exhibit multiple patterns of infection indicators. The prevalence rate of HDV infection among blood donors in Wuhan is extremely low. However, the risk of asymptomatic occult hepatitis B infection (OBI) blood donors being co-infected with HDV should not be overlooked in areas with high prevalence of HBV.
Humans ; Blood Donors ; Hepatitis B/blood* ; China/epidemiology* ; Adult ; Male ; Female ; Hepatitis D/epidemiology* ; Middle Aged ; Hepatitis B virus/immunology* ; Hepatitis B Antibodies/blood* ; Young Adult ; DNA, Viral/blood* ; Hepatitis B Surface Antigens/blood* ; Prevalence ; Adolescent

The chemical constituents from leaves of Cyclocarya paliurus were isolated and purified by chromatography on silica gel, C_(18) reverse-phase silica gel, and Sephadex LH-20 gel, as well as semi-preparative high-performance liquid chromatography. Six compounds were identified by UV, IR, NMR, MS, calculated ECD, and comparison with literature data as cyclopaloside D(1), boscialin(2),(5R,6S)-6-hydroxy-6-[(E)-3-hydroxybut-1-enyl]-1,1,5-trimethylcyclohexanone(3), 3S,5R-dihydroxy-6R,7-megastigmadien-9-one(4), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(5), and gingerglycolipid A(6), respectively. Among them, compound 1 was identified as a new tetralone glycoside, and compounds 2-6 were isolated from leaves of C. paliurus for the first time. Furthermore, compound 1 exhibited strong antioxidant activity, with the IC_(50) of(454.20±31.81)μmol·L~(-1) and(881.82±42.31)μmol·L~(-1) in scavenging DPPH and ABTS free radicals, respectively.
Plant Leaves/chemistry* ; Glycosides/isolation & purification* ; Juglandaceae/chemistry* ; Tetralones/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification*