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.

ObjectiveTo analyze the incidence rate and mortality of acute myocardial infarction (AMI) and their changing trends among the registered residents in Xiaoshan District, Hangzhou City from 2017 to 2023, so as to provide references for formulating policies related to AMI prevention. MethodsThe morbidity and mortality data of AMI among the registered residents in Xiaoshan District from 2017 to 2023 were collected through the Hangzhou Chronic Disease and Death Cause Monitoring System. Software such as Excel 2019, SPSS 25.0 and Joinpoint 4.9.1.0 were used to calculate the incidence rate, mortality, and average annual percentage change (AAPC) of AMI. ResultsFrom 2017 to 2023, the average annual crude incidence rate, age-standardized incidence rate using China standard population (ASIRC), and the age-standardized incidence rate using World standard population (ASIRW) of AMI in Xiaoshan District were 48.25/100 000, 29.14/100 000, and 21.64/100 000, respectively, and, from which the AAPCs were 5.495%, 6.010%, and 6.533%, respectively, all showing an upward trend. The average annual crude mortality rate, the age-standardized mortality rate using China standard population (ASMRC), and the age-standardized mortality rate using World standard population (ASMRW) were 11.76/100 000, 6.52/100 000, and 4.71/100 000, respectively, from which the AAPCs were -9.669%, -10.433% and -9.615%, respectively, all showing a downward trend. The average annual crude incidence rate of AMI was higher in males (65.87/100 000) than that in females (31.31/100 000). Moreover, the average annual crude mortality rate of AMI was higher in males (14.08/100 000) than that in females (9.52/100 000), and the difference was statistically significant (all P<0.001) .After age grouping, the crude incidence rate of AMI among the residents aged 35-, 45-, 55-, and 65- years in Xiaoshan District from 2017 to 2023 showed an upward trend over time, with AAPCs of 16.993%, 17.149%, 8.523%, and 5.002%, respectively. While the crude mortality rate in residents aged 35-, 75-, and 85-102 years showed an decreasing trend over time, with AAPCs of -23.977%, -15.467%, and -17.415%, respectively, but there was no statistically significant difference in the trends in incidence rate and mortality of other age groups (all P>0.05). ConclusionThe situation of AMI prevention and control among the registered residents in Xiaoshan District is not optimistic, and targeted measures should be strengthened for the male residents aged ≥35 years old.

Objective: To analyze the impact of maternal metal exposure during early pregnancy on the physical development of offspring at 1 and 3 years of age, so as to provide scientific evidence for reducing the adverse effects of heavy metals on their health. Methods: From 2024 to 2018, a total of 1 588 mother child pairs from the Jiangsu Birth Cohort (JBC) were included in this study. Multiple linear regression models, generalized estimating equations (GEE), and weighted quantile sum (WQS) regression models were used to assess the associations between 24 urinary metal mass concentrations (adjusted for specific gravity, SG) during early pregnancy and offspring growth outcomes, including length/height for age Z score(HAZ), weight for age Z score(WAZ), weight for length/height Z score(WHZ), and head circumference for age Z score(HCAZ) at 1 and 3 years of age. Results: After adjusting for confounders, GEE analysis revealed that each natural log unit increase in maternal urinary concentrations of vanadium, tin, cerium, lead, and uranium during early pregnancy was associated with an average reduction in HCAZ by 14.29%, 4.82%, 2.62 %, 5.04 %, and 8.33%, respectively, at 1 and 3 years of age (FDR- P <0.05). Multiple linear regression analysis revealed that increased urinary vanadium concentration was associated with reduced HAZ at 1 year of age, while increased urinary concentrations of vanadium, chromium, tin, antimony, and uranium were associated with reduced HCAZ at 1 year of age (FDR- P <0.05). In the WQS regression model, each unit increase in the WQS index was associated with a 22.64% reduction in HCAZ at 1 year of age, with tin (22.2%) contributing the highest weight, followed by uranium (16.2%), lead (11.5%), vanadium (10.0%), arsenic (6.5%), and chromium (5.0%). Conclusions Prenatal exposure to specific metals and their mixtures may significantly impact the physical development of offspring at 1 and 3 years of age, particularly head circumference. These findings highlight the need to enhance monitoring of maternal metal exposure during early pregnancy to reduce the potential health risks posed by environmental metal pollution to infants and young children.

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Objective To investigate the clinical efficacy of Qiangli Pipa Syrup for the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),and to observe its effects on pulmonary function and interleukin 6(IL-6),C-reactive protein(CRP)and procalcitonin(PCT)levels in the patients.Methods Eighty patients with AECOPD of phlegm-heat obstructing the lung syndrome were randomly divided into the observation group and the control group,with 40 patients in each group.Patients in the control group were treated with conventional western medicine,and patients in the observation group were treated with Qiangli Pipa Syrup on the basis of treatment for the control group.Both groups were treated for 5 days.The two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores(including cough,expectoration,shortness of breath,and wheezing),pulmonary function parameters[the forced expiratory volume in one second(FEV1)and the ratio of FEV1 to the forced vital capacity(FVC)(FEV1/FVC)],blood gas indicators[arterial partial pressure of oxygen(PaO2),blood oxygen saturation(SaO2)and arterial partial pressure of carbon dioxide(PaCO2)]and the levels of the inflammatory factors of IL-6,CRP,and PCT before and after treatment.Moreover,the clinical efficacy and safety of the patients in the two groups were evaluated.Results(1)After 5 days of treatment,the total effective rate of the observation group was 95.00%(38/40),and that of the control group was 77.50%(31/40).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores of cough,expectoration,shortness of breath,and wheezing in the two groups were reduced compared with those before treatment(P＜0.05),and the reduction in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the pulmonary function parameters of FEV1/FVC and FEV1 in the two groups were improved compared with those before treatment(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the blood gas indicators of PaO2 and SaO2 levels in the two groups were increased compared with those before treatment(P＜0.05),and the PaCO2 level was decreased compared with that before treatment(P＜0.05).The increase of PaO2 and SaO2 levels and the decrease of PaCO2 level in the observation group were significantly superior to those in the control group(P＜0.05).(5)After treatment,the serum levels of inflammatory factors of IL-6,CRP,and PCT in the two groups were lower than those before treatment(P＜0.05),and the reduction in the observation group was significantly superior to that in the control group(P＜0.05).(6)The incidence of adverse reactions in the observation group was 10.00%(4/40),while that in the control group was 7.50%(3/40).There was no significant difference between the two groups(P＞0.05).Conclusion Qiangli Pipa Syrup exerts certain effect in treating patients with AECOPD of phlegm-heat obstructing the lung syndrome,which can effectively relieve the clinical symptoms,improve the pulmonary function and blood gas indicators,and inhibit inflammatory response of the patients,with high safety profile.

BACKGROUND:Seed cells are seeded on three-dimensional scaffold materials,and three-dimensional culture in bioreactors is a common in vitro tissue engineering culture method,but the changes in cell proliferation and metabolic patterns in bioengineered blood vessel construction are still unclear. OBJECTIVE:To explore the metabolic changes of cells such as oxygen consumption and their causes during the whole process of biological vascular tissue construction by in vitro bioreactor. METHODS:The self-built vascular bioreactor system was used as the platform;bovine vascular smooth muscle cells were used as the seed cells,and a conventional CO2 incubator provided the external gas environment for the cultivation process.Seed cells were seeded on a tubular porous polyglycolic acid scaffold material for three-dimensional culture,and the whole process included a one-week resting period and a seven-week pulsating tensile stress stimulation loading period.A non-invasive monitoring system was built,and the optical dissolved oxygen patch method was used to monitor the changes of dissolved oxygen in the culture solution in the reactor,and the glucose consumption and lactic acid production were measured by regular sampling.CCK-8 assay was used to determine the proliferation of smooth muscle cells on polyglycolic acid three-dimensional scaffold materials.Nicotinamide adenine dinucleotide oxidation state and reduction state ratio(NAD+/NADH)was utilized to understand cell proliferation and metabolism in the early stage of culture.RT-qPCR and western blot assay were applied to detect the expression of proliferation-related genes(Ki67)and glycolysis-related genes(GLUT-1,LDHA). RESULTS AND CONCLUSION:(1)The dissolved oxygen level in the culture solution was(4.314±0.380)mg/L from the cell injection to the end of the resting period(the first week),and gradually stabilized at(1.960±0.866)mg/L after the tensile stress stimulation(the last seven weeks);the two had significant changes(P<0.05).(2)The ratio of glucose consumption to lactic acid production in the cell culture medium YL/G increased rapidly after the cells were injected,and the highest value was above 1 on the fifth day,and then slow down to 0.5(The mean value of YL/G in the resting period was 0.89 and the mean value in the pressurized period was 0.57,P<0.05).(3)CCK-8 assay results showed that A450 value gradually increased after the cells were injected,and reached the highest value on the fifth day,reaching 3.17,and then slowly decreased.At the same time,it was found that Ki67 mRNA was up-regulated on the third day of culture,and then declined.The expression level of Ki67 protein was higher from the third day to the fifth day.(4)The detection of NAD+/NADH showed that the increase was obvious from the fifth to the seventh day after the injection of cells,and the expression of glycolysis-related genes(GLUT-1 and LDHA)was up-regulated and changed synchronously,and the relative expression was higher in the first five days.(5)The results showed that the tissue-engineered blood vessels were constructed using the vascular bioreactor and the smooth muscle cells in the early stage mainly proliferated and exhibited a metabolic feature of low oxygen consumption.The metabolic characteristics of high oxygen consumption were observed during the pulsatile tensile stress stimulation stage.

Objective: To understand the survival status and influencing factors of first-ever stroke patients, so as to provide evidence for improving the quality of life and prognosis of stroke patients. Methods: Demographic information, medical history, smoking history, and alcohol consumption history of newly diagnosed stroke cases first reported in 2017 in Xiaoshan District were collected through the Hangzhou Chronic Disease Surveillance and Management System. Patients were followed up for 5 years, with stroke death as the outcome event. The survival rate was calculated using the Kaplan-Meier method, and factors affecting survival time of first-ever stroke patients were identified using a multivariable Cox proportional hazard regression model. Results: A total of 3 886 patients first-ever stroke patients were included, the cases of cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, and stroke unspecified as to whether it was hemorrhagic or ischemic (unspecified) accounted for 86.93%, 11.45%, 1.06% and 0.57%, respectively. There were 2 047 males (52.68%) and 1 839 females (47.32%), with a mean onset age of (72.01±11.61) years. By the end of the follow-up on December 31, 2022, 906 patients died from stroke, with a median follow-up time of 62.00 (interquartile range, 35.00) months. The 1-year survival rate was 87.35% (95%CI: 86.30%-88.41%), the 3-year survival rate was 82.11% (95%CI: 80.88%-83.34%), and the 5-year survival rate was 76.64% (95%CI: 75.26%-78.02%), respectively. Multivariable Cox proportional hazard regression analysis showed that onset age of ≥75 years (HR=5.543, 95%CI: 3.822-8.039), being treated at township-level hospitals (HR=5.934, 95%CI: 4.027-8.743), history of hypertension (HR=1.566, 95%CI: 1.317-1.863), history of chronic ischemic heart disease (HR=1.611, 95%CI: 1.362-1.906), smoking history (HR=1.455, 95%CI: 1.190-1.778), alcohol consumption history (HR=1.323, 95%CI: 1.067-1.641), stroke subtype of intracerebral hemorrhage (HR=3.442, 95%CI: 2.923-4.053) and unspecified (HR=6.843, 95%CI: 4.353-10.756) were associated with higher mortality risk among first-ever stroke patients. Conclusion The 5-year survival rate of first-ever stroke patients was 76.64%, which was influenced by age of onset, hospital level for diagnosis and treatment, stroke subtype, medical history, smoking and alcohol consumption.

Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

As a novel iron-dependent form of cell death, ferroptosis is characterized by the excessive accumulation of phospholipids containing polyunsaturated fatty acids (PUFA) on the cell membrane and peroxidation. Lipid droplets are always in the dynamic transition of generation and decomposition, play a central role in regulating lipid metabolism, and are always in the dynamic transition of generation and decomposition. Lipid droplet metabolism is closely related to the occurrence of ferroptosis and plays an important role in the disease caused by ferroptosis. This review firstly focuses on the lipid droplet metabolism process and its effects on the storage and release of PUFA, and further elucidates the regulatory mechanism and key regulatory proteins of lipid drop metabolism on ferroptosis, in order to reveal the intrinsic relationship between lipid droplets and ferroptosis, and provide a new strategy for disease prevention and treatment.

Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.