Aim To investigate the effects of lycopene on myocardial microvascular remodeling and elucidate its underlying mechanisms via the LXR/PI3K/Akt pathway.Methods 50 SD rats were selected to establish a coronary microcirculation disorder model and divided into sham,model and low/mid/high concentration lycopene groups.Left ven-tricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in rats were detected using echocardiography,creatine kinase(CK),lactate dehydrogenase(LDH),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF)were detected using ELISA,matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-2(MMP-2)and PI3K/Akt pathway related protein expression were detected using Western blot,and liver X receptor α(LXRα)and liver X receptor β(LXRβ)expression were detected using immunohistochemical staining.In vitro,a hypoxia model of myo-cardial microvascular endothelial cells(MCMEC)was established,with groups including control,hypoxia,hypoxia+low/mid/high concentration lycopene,LXR/PI3K/Akt pathway inhibitor group and mitochondrial fission inhibitor group.Cell viability was detected using CCK-8,LXRα and LXRβ were detected using immunofluorescence,superoxide dismutase(SOD),reactive oxygen species(ROS),VEGF and PDGF levels were detected using ELISA,mitochondrial function-re-lated proteins(Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1)and MMP-9,MMP-2 and PI3K/Akt pathway related proteins were detected using Western blot,and myocardial tissue injury was evaluated using HE staining.Results Compared with the sham group,the model group exhibited severe myocardial injury,with increased levels of LVEDD,LVESD,CK and LDH,decreased LVEF and LVFS,downregulated expression of VEGF,PDGF,MMP-9 and MMP-2,de-creased expression of p-PI3K/PI3K and p-Akt/Akt,and downregulated expression of LXRα and LXRβ.In cells,com-pared with the control group,the hypoxia group showed decreased cell viability,downregulated expression of VEGF,PDGF,MMP-9,and MMP-2,and decreased expression of p-PI3K/PI3K and p-Akt/Akt.Lycopene treatment could ef-fectively reverse the above changes and increase the expression of LXRα and LXRβ.Moreover,lycopene could also re-verse and modulate the characteristic alterations of Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1 induced by LXR/PI3K/Akt pathway inhibitors or mitochondrial fission inhibitors.Conclusion Lycopene enhances mitochondrial activi-ty,reduces oxidative stress and improves myocardial microvascular remodeling by activating the LXR/PI3K/Akt pathway.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Aim To investigate the effects of lycopene on myocardial microvascular remodeling and elucidate its underlying mechanisms via the LXR/PI3K/Akt pathway.Methods 50 SD rats were selected to establish a coronary microcirculation disorder model and divided into sham,model and low/mid/high concentration lycopene groups.Left ven-tricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in rats were detected using echocardiography,creatine kinase(CK),lactate dehydrogenase(LDH),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF)were detected using ELISA,matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-2(MMP-2)and PI3K/Akt pathway related protein expression were detected using Western blot,and liver X receptor α(LXRα)and liver X receptor β(LXRβ)expression were detected using immunohistochemical staining.In vitro,a hypoxia model of myo-cardial microvascular endothelial cells(MCMEC)was established,with groups including control,hypoxia,hypoxia+low/mid/high concentration lycopene,LXR/PI3K/Akt pathway inhibitor group and mitochondrial fission inhibitor group.Cell viability was detected using CCK-8,LXRα and LXRβ were detected using immunofluorescence,superoxide dismutase(SOD),reactive oxygen species(ROS),VEGF and PDGF levels were detected using ELISA,mitochondrial function-re-lated proteins(Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1)and MMP-9,MMP-2 and PI3K/Akt pathway related proteins were detected using Western blot,and myocardial tissue injury was evaluated using HE staining.Results Compared with the sham group,the model group exhibited severe myocardial injury,with increased levels of LVEDD,LVESD,CK and LDH,decreased LVEF and LVFS,downregulated expression of VEGF,PDGF,MMP-9 and MMP-2,de-creased expression of p-PI3K/PI3K and p-Akt/Akt,and downregulated expression of LXRα and LXRβ.In cells,com-pared with the control group,the hypoxia group showed decreased cell viability,downregulated expression of VEGF,PDGF,MMP-9,and MMP-2,and decreased expression of p-PI3K/PI3K and p-Akt/Akt.Lycopene treatment could ef-fectively reverse the above changes and increase the expression of LXRα and LXRβ.Moreover,lycopene could also re-verse and modulate the characteristic alterations of Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1 induced by LXR/PI3K/Akt pathway inhibitors or mitochondrial fission inhibitors.Conclusion Lycopene enhances mitochondrial activi-ty,reduces oxidative stress and improves myocardial microvascular remodeling by activating the LXR/PI3K/Akt pathway.

Objective:To analyze the significance of total vitamin D(tVD),total procollagen type Ⅰ amino-terminal propeptide(tPINP)and β-CrossLaps(β-CTx)in the staging and prognosis of patients with multiple myeloma(MM).Methods:A total of 54 patients with newly diagnosed MM admitted to the Second Affiliated Hospital of Fujian Medical University from 2020 to 2022 were selected as the observation group(MM group),and 50 healthy persons who underwent physical examinations in our hospital were selected as the control group.The expression levels of tVD,tPINP and β-CTx in the two groups were detected by chemiluminescence method.The differences in the expression levels of tVD,tPINP and β-CTx among MM patients at different ISS stages were analyzed.The expression levels of tVD,tPINP and β-CTx in MM patients with different levels of hemoglobin(Hb),serum calcium(Ca),creatinine(Crea),albumin(ALB),β2-microglobulin(β2-MG)and lactate dehydrogenase(LDH)were compared.The correlations between the expression levels of tVD,tPINP,β-CTx and the aforementioned clinical parameters were analyzed,respectively.The relationship between the expression levels of tVD,tPINP,β-CTx and the progression-free survival(PFS)of MM patients was analyzed.Results:The expression level of tVD in the MM group was significantly lower than that in the control group(21.73±14.45 ng/ml vs 30.78±9.94 ng/ml,P=0.022).The expression level of β-CTx in the MM group was significantly higher than that in the control group(1.43±0.99 ng/ml vs 0.53±0.29 ng/ml,P=0.013).The tVD level in MM patients with ISS stage Ⅰ-Ⅱ was significantly higher than that of MM patients with ISS stage Ⅲ(29.50±14.59 ng/ml vs 12.62±7.73 ng/ml,P=0.028),indicating that the higher the ISS stage,the lower the tVD level.The tPINP andβ-CTx levels in MM patients with high Ca levels(＞2.65 mmol/L)were significantly higher than those in patients with low Ca levels(≤ 2.65 mmol/L)(P=0.016,P=0.021).The tVD level of MM patients was positively correlated with the ALB level(r=0.570),tPINP was positively correlated with Ca and β2-MG levels(r=0.791,r=0.673),and β-CTx was positively correlated with tPINP level(r=0.616).The PFS of the low tVD expression group was significantly lower than that of the high tVD expression group(P=0.041).Conclusion:The expression level of tVD is decreased in MM patients,which can be used as an indicator to evaluate the disease stage and prognosis of the patients.The β-CTx expression level is increased in MM patients.tPINP and β-CTx may be correlated with clinical symptoms such as osteolytic lesions and renal function changes in MM patients.

BACKGROUND:Inflammation is one of the important factors that induce cerebral ischemia-reperfusion injury.Studies have shown that electroacupuncture can effectively reduce inflammation after ischemic stroke and improve the symptoms of neurological deficits,but the mechanism is not clear. OBJECTIVE:To observe the effect of electroacupuncture on Toll-like receptor 4/nuclear factor-κB in rats with cerebral ischemia-reperfusion injury. METHODS:Forty-eight male Sprague-Dawley rats were randomly divided into sham operation group,model group and electroacupuncture group,with 16 rats in each group.The rat model of cerebral ischemia-reperfusion injury was prepared by middle cerebral artery occlusion.At 24 hours after modeling,the rats in the electroacupuncture group were treated with electroacupuncture,once a day,20 minutes each time,for a total of 5 days.The sham operation group and the model group did not do any intervention.After 5 days of intervention,Longa method was used to evaluate the degree of neurological injury in rats.Triphenyl tetrazolium chloride staining and hematoxylin-eosin staining were used to measure the volume of cerebral infarction and the pathological changes of brain tissue in rats.Serum interleukin-6,interleukin-18 and tumor necrosis factor-α were detected by ELISA.Expressions of Toll-like receptor 4 and nuclear factor-κB in the cerebral cortex at mRNA and protein levels were detected by fluorescence quantitative PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the neurological function scores,serum interleukin-6,interleukin-18,and tumor necrosis factor-α levels,Toll-like receptor 4 and nuclear factor-κB mRNA and protein expression levels were significantly higher in the model group(P＜0.01).Compared with the model group,electroacupuncture significantly reduced the neurological function scores,serum interleukin-6,interleukin-18,and tumor necrosis factor-α levels,Toll-like receptor 4 and nuclear factor-κB mRNA and protein expression levels(P＜0.05,P＜0.01).Compared with the sham operation group,the volume of cerebral infarction in the model group increased significantly(P＜0.01).Compared with the model group,the volume of cerebral infarction in the electroacupuncture group decreased(P＜0.05).In the model group,the arrangement of neurons was disordered,some nerve cells disappeared,nuclei presented with pyknosis and incomplete structure.After electroacupuncture intervention,the degree of neuronal degeneration and neuronal loss in the cerebral cortex of rats were reduced compared with those in the model group.To conclude,electroacupuncture can significantly improve the neurobehavior of rats with cerebral ischemia-reperfusion injury,reduce brain tissue injury,and effectively reduce the level of serum inflammatory factors.The mechanism may be related to the inhibition of Toll-like receptor 4/nuclear factor-κB signaling pathway.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Objective: Anxious depression is a prevalent characteristic observed in Asian psychiatric patients diagnosed with major depressive disorder (MDD). This study aims to investigate the prevalence and clinical presentation of anxious depression in Taiwanese individuals diagnosed with MDD. Methods: We recruited psychiatric outpatients aged over 18 who had been diagnosed with MDD through clinical interviews. This recruitment took place at five hospitals located in northern Taiwan. We gathered baseline clinical and demographic information from the participants. Anxious depression was identified using a threshold of an anxiety/somatization factor score ≥7 on the 21-item Hamilton Rating Scale for Depression (HAM-D). Results: In our study of 399 patients (84.21% female), 64.16% met the criteria for anxious depression. They tended to be older, married, less educated, with more children, and an older age of onset. Anxious depression patients had higher HAM-D and Clinical Global Impression–Severity scale score, more panic disorder (without agoraphobia), and exhibited symptoms like agitation, irritability, concentration difficulties, psychological and somatic anxiety, somatic complaints, hypochondriasis, weight loss, and increased insight. Surprisingly, their suicide rates did not significantly differ from non-anxious depression patients. This highlights the importance of recognizing and addressing these unique characteristics. Conclusion Our study findings unveiled that the prevalence of anxious depression among Taiwanese outpatients diagnosed with MDD was lower compared to inpatients but substantially higher than the reported rates in European countries and the United States. Furthermore, patients with anxious depression exhibited a greater occurrence of somatic symptoms.