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 investigate disparities in health levels among populations across different regions of China and analyze the relationship between these disparities and regional, social, and economic factors, and to provide recommendations to promote health equity. Methods Based on the data from the Seventh National Population Census, this study employed spatial autocorrelation analysis and the spatial Durbin model to conduct spatial and temporal analyses of the health status of the national population from 2012 to 2021, focusing on the regional distribution of health levels and related influencing factors. Results 1. Regional disparities: The mortality rate in Gansu Province rose from 6.05‰ in 2012 to 8.26‰ in 2021, whereas the mortality rate in eastern provinces such as Hainan Province was relatively low in 2021 (5.39‰). 2. Spatial clustering: The spatial correlation of mortality rates was weak (Moran's I: 0.134-0.245), and the high mortality clusters showed a shift from southwest to northeast region. 3. Influencing factors: Economic conditions, education quality, urbanization levels, and healthcare resources significantly impacted population mortality rates. Conclusion The present study identifies pronounced regional disparities in population health, providing a scientific basis for formulating targeted healthcare policies. Additionally, this study highlights the critical importance of spatial analysis in understanding and addressing public health issues to advance health equity.

Objective To explore the mediating role of activities of daily living (ADL) in pain and depressive symptoms in the elderly in China. Methods Utilizing the data from 2020 China Health and Retirement Longitudinal Study, 4403 Chinese elderly individuals aged ≥ 60 years old were selected as the research subjects. Depression Scale (CES-D 10) of the Center for Epidemiological Survey and ADL scale were used in the study. The PROCESS4.1 macro was used to test the mediating effect of daily living activities between pain and depressive symptoms, and the Bootstrap method was applied for verification of the mediating variables. Results A total of 2368 cases of depressive symptoms were detected in the elderly in China, with a detection rate of 53.78%. Pain was positively correlated with depressive symptoms (r=0.27, P<0.01), and activities of daily living were negatively correlated with pain and depressive symptoms (r=-0.27, -0.337, P<0.01). The results showed that the total effect value of pain on depressive symptoms was 0.33, the direct effect value was 0.24, and the mediating effect value of daily living activities was 0.09, accounting for 27.27%. Conclusion Pain and activities of daily living are important factors influencing depressive symptoms in the elderly, and activities of daily living play a partial mediating role in the relationship between pain and depressive symptoms in the elderly.

Objective To investigate the effect of Ophiopogonin D on lipopolysaccharide(LPS)-induced apoptosis of alveolar epithelial cells by regulating the interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A549 AT Ⅱ cells cultured in vitro were randomly divided into four groups:control group,LPS group,LPS+Ophiopogonin D group,LPS+Ophiopogonin D+colivelin(JAK2/STAT3 signal activator)group,except for the control group,and cells in all other groups were established injury models while being grouped with Ophiopogonin D and colivelin for treatment.Cell counting kit-8(CCK-8)experiment and flow cytometry were applied to detect cell proliferation and apoptosis in each group;Western blotting was applied to detect the expression of IL-6/JAK2/STAT3 signaling pathway proteins of cells in each group.Results The apoptosis rates of A549 cells in control group,LPS group,LPS+Ophiopogonin D group and LPS+Ophiopogonin D+colivelin group were(2.52±0.73)％,(52.43±4.14)％,(1.67±0.52)％and(47.94±3.43)％;IL-6 protein levels were 0.14±0.03,0.49±0.05,0.17±0.04 and 0.45±0.06,and p-JAK2/JAK2 protein levels were 0.17±0.04,0.64±0.08,0.19±0.06 and 0.61±0.07;p-STAT3/STAT3 protein levels were 0.20±0.06,0.69±0.10,0.22±0.07 and 0.65±0.09;the apoptosis rates of AT Ⅱ cells were(3.01±0.69)％,(55.16±3.94)％,(2.35±0.71)％and(50.28±3.78)％;the levels of IL-6 protein were 0.11±0.03,0.87±0.13,0.19±0.04 and 0.84±0.12;the p-JAK2/JAK2 protein levels were 0.13±0.04,0.56±0.08,0.15±0.03 and 0.53±0.07;p-STAT3/STAT3 protein levels were 0.30±0.08,0.79±0.14,0.33±0.09 and 0.75±0.13.The above indexes:control group,LPS+Ophiopogonin D group compared with LPS group,LPS+Ophiopogonin D+colivelin group compared with LPS+Ophiopogonin D group,the differences were statistically significant(all P＜0.05).Conclusion Ophiopogonin D can reduce LPS induced inflammation and oxidative stress levels by inhibiting the activation of IL-6/JAK2/STAT3 signaling pathway,ultimately reducing LPS-induced apoptosis of alveolar epithelial cells.

Objective To investigate the effect of epidermal growth factor tyrosine kinase inhibitor AG1478 combined with oxaliplatin(OXA)on non-small cell lung cancer cells H1299.Methods H1299 cells were divided into control group(conventional culture,without drug),OXA-25,-50,-100 groups(25,50 and 100 μmol·L-1 OXA),AG-20 group(20 μmol·L-1AG1478)and OXA+AG group(25 μmol·L-1 OXA and 20 μmol·L-1AG1478).Detection of cell survival rate by MTT assay and calculation of half inhibitory concentration(IC50).Reactive oxygen species(ROS)probe H2DCFDA was used to detect ROS levels.Autophagy of H1299 cells was detected by MDC method.Western blot was used to detect the expression levels of phosphorylated-phosphoinositide 3-kinase(p-PI3 K),phosphorylated-protein kinase B(p-AKT),autophagy protein(Beclin-1)and microtubule associated protein light chain 3-Ⅱ(LC3-Ⅱ).Results The IC50 of OXA on H1299 cells was 91.09 μmol·L-1.The IC50 of AG1478 on H1299 cells was 31.83 μmol·L-1.The relative ROS level were 1.00±0.03,1.15±0.02,1.76±0.04,2.89±0.02,1.05±0.01 and 3.20±0.03,respectively;the relative MDC levels were 1.00±0.04,1.10±0.02,1.16±0.02,1.46±0.04,1.04±0.01 and 1.31±0.02,respectively;the relative expression levels of p-PI3K protein were 1.12±0.05,0.88±0.06,0.72±0.07,0.60±0.05,0.91±0.07 and 0.64±0.09,respectively;the relative expression levels of p-AKT protein were 1.09±0.04,0.87±0.08,0.77±0.07,0.63±0.05,0.76±0.05 and 0.46±0.03,respectively;the relative expression levels of Beclin-1 protein were 0.82±0.03,0.91±0.04,1.06±0.28,1.11±0.03,0.87±0.04 and 1.27±0.10,respectively;the relative expression levels of LC3-Ⅱ protein were 0.65±0.08,0.82±0.11,1.08±0.12,1.38±0.09,0.72±0.11 and 1.38±0.15,respectively.Compared the OXA+AG group and the OXA single group with the control group,compared the OXA+AG group with the OXA single group,there were statistically significant differences in the above indicators(P＜0.05,P＜0.01).Conclusion AG1478 combined with OXA can increase ROS levels in non-small cell lung cancer cells H1299 and inhibit the activation of PI3K signaling pathway,thus inducing autophagy.

Methods: (i) Animal experiments. This study conducted experiments using specific pathogen-free (SPF) grade male C57BL/6J wild-type (WT) mice and APP/PS1 double transgenic mice. The animals were divided into three groups: WT group (WT mice, n = 5, receiving distilled water daily), APP/PS1 group (APP/PS1 double transgenic mice, n = 5, receiving distilled water daily), and BSTSD group [APP/PS1 double transgenic mice, n = 5, treated with BSTSD suspension at a dosage of 27 g/(kg·d) for 90 d]. Cognitive function was assessed using the Morris water maze (MWM). Post-experiment, hippocampal tissues were collected for analysis of pyramidal cell and synaptic morphology through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). (ii) Cell experiments. The HT-22 cells were divided into control group (untreated), Aβ25-35 group (treated with 20 μmol/L Aβ25-35 for 24 h), icariin group (pre-treated with 20 μmol/L icariin for 60 min, followed by 20 μmol/L Aβ25-35 for an additional 24 h), and icariin + LY294002 group [treated with 20 μmol/L icariin and 20 μmol/L LY294002 (an inhibitor of the phosphoinostitide 3-kinases (PI3K) signaling pathway) for 60 min, then exposed to 20 μmol/L Aβ25-35 for 24 h], and cell viability was measured. Western blot was used to detect the expression levels of synapse-associated proteins [synaptophysin (SYP) and postsynaptic density-95 (PSD-95)] and PI3K signaling pathway associated proteins [phosphorylated (p)-PI3K/PI3K, p-protein kinase B (Akt)/Akt, and p-mechanistic target of rapamycin (mTOR)/mTOR]. Results: (i) Animal experiments. Compared with APP/PS1 group, BSTSD group showed that escape latency was significantly shortened (P < 0.01) and the frequency of crossing the original platform was significantly increased (P < 0.01). Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly, nuclear staining was uniform, and vacuole-like changes were reduced after BSTSD treatment. TEM showed that the length of synaptic active zone in BSTSD treatment group was increased compared with APP/PS1 group (P < 0.01), and the width of synaptic gap was decreased (P < 0.01). (ii) Cell experiments. Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L (P > 0.05), and alleviated the cell viability decline induced by Aβ25-35 (P < 0.01). Western blot results showed that compared with Aβ25-35 group, the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased (P < 0.01), while the protein expression levels of SYP and PSD-95 were increased (P < 0.01). These effects were blocked by LY294002 (P < 0.01). Conclusion BSTSD and icariin enhance cognitive function and synaptic integrity in AD models and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway.

The compounds were isolated and purified by silica gel, MCI, Sephadex LH-20 and semi-preparative high performance liquid chromatography. The structures of the compounds were determined by NMR and MS spectroscopic data. Twenty monomer compounds were isolated from the ethyl acetate extract of Lindera reflexa root from Hunan province, and identified as: (1″S,3″S,6″R)-2′,4′,6′-trihydroxy-3′-[1″-(3″-hydroxy)-p-menthanyl]-chalcone (1), sumadain D (2), quercetin (3), catechin (4), epicatechin (5), N-cis-feruloyltyramine (6), N-trans-feruloyltyramine (7), N-trans-feruloyl-3-methoxytyramine (8), flavifloramides B (9), northalifoline (10), isolariciresinol (11), syringaresinol (12), pinoresinol (13), medioresinol (14), dehydroconiferyl alcohol (15), 4-methoxyl-denudaquinol (16), miliusanal (17), syringic acid (18), abscisic acid (19), (E)-cinnamyl-(E)-cinnamate (20). Compound 1 is a new compound, and compounds 2‒20 have been isolated from Lindera reflexa for the first time. The results showed that compounds 1, 2, 3 and 16 could significantly reduce the survival ability of MGC-803 cells with IC₅₀ values of 5.58, 23.41, 25.72 and 20.96 μmol·L^-1, respectively. Compounds 5 and 20 can reduce the survival ability of MGC-803 cells with IC₅₀ values of 98.83 and 89.26 μmol·L^-1, respectively.

Protein disulfide isomerase A6 (PDIA6) is closely related to inflammation and endoplasmic reticulum stress. To obtain the glycosyl derivatives of benzophenone polyphenols targeting PDIA6 with strong anti-inflammatory effects, twenty-five target glycosyl derivatives were synthesized by Friedel-Crafts acylation and deacetylation reaction, starting from the substituted benzophenone and α-bromoacetyl saccharide, and their interactions with PDIA6 were quantitatively investigated by bio-layer interferometry (BLI) technique. Their in vitro anti-inflammatory properties were also evaluated. The results showed that target compounds 4b, 10b, 17b, 18b, and 25b not only exhibit high affinity with PDIA6, but also present strong anti-inflammatory abilities. Above results suggest that this class of compounds can affect the signaling pathways related to inflammation by directly acting on PDIA6. In particular, such compounds exhibit the strong inhibitory effects on IL-1β and IL-6 release, suggesting the potential development prospect in the treatment of inflammatory diseases.

Trace elements (TEs), also known as micronutrients in biology, are trace components required by the human body, accounting for 0.005% to 0.01% of body weight. Although TEs are present in small quantities in the human body, they play significant roles in cellular metabolism, enzyme activity regulation, immune function, nerve conduction, and bone health. In this review, the effects of TEs (zinc, iron, magnesium, selenium, copper, chromium, and manganese) for modulating biological functions on organisms are comprehensively analyzed and summarized. The mechanisms of various TEs in immune system, enzymatic reaction, oxidative stress, physical growth, and blood glucose regulation are deeply discussed, emphasizing the indispensable role of TEs in maintaining normal physiological functions of body. In addition, the future research directions of TEs are also prospected, including the mechanism of action, intake, metabolism, and storage of TEs at the cellular level. This review will provide useful information to further understand the biological effects and the application of TEs.

Objective:To explore the anti-inflammatory effect and safety of two non-steroidal anti-inflammatory drugs in the phacoemulsification combined with intraocular lens (IOL) implantation.Methods:A randomized, double-blind, clinical trial was conducted.A total of 90 age-related cataract patients (90 eyes) who were diagnosed in Qingdao Eye Hospital Affiliated to Shandong First Medical University were enrolled from October 2020 to February 2021.The patients were randomized to diclofenac sodium group and bromofenac sodium group by random number table method, with 45 cases (45 eyes) in each group.All patients underwent phacoemulsification combined with IOL implantation, and 0.1% diclofenac sodium eye drops (preservative-free), 4 times a day, and 0.1% pramiphene eye drops, 2 times a day were applied in the perioperative period.The duration of continuous medication treatment and follow-up time were 6 weeks.The subjective symptoms of the patients were scored before and after surgery.The amount of tear fluid secretion was detected by Schirmer I test, and the tear film breakup time was recorded with the Oculus dry eye analyzer.Corneal fluorescein staining was observed under a slit lamp microscope with cobalt blue light.Anterior chamber flash was measured by slit-lamp biomicroscopy.The thickness of central macular area and the presence of macular cystoid edema was measured by optical coherence tomography.Visual acuity, noncontact intraocular pressure (IOP) and the drug safety were examined and evaluated.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Qingdao Eye Hospital (No.[2020]60).All patients were informed about the surgery and postoperative medication and signed the informed consent form.Results:All subjects had no intraoperative complications, and completed treatment and follow-up as required.The preoperative, 1-day postoperative, 1-week postoperative, 6-week postoperative subjective symptom scores were (0.47±0.73), (0.56±0.62), (0.33±0.48), and (0.51±0.66) points in the diclofenac group, and (0.47±0.51), (0.75±0.61), (0.64±0.65), and (0.78±0.77) points in the bromfenac group.There were statistically significant differences in the subjective symptom scores at different time points between the two groups ( Fgroup=5.001, P=0.028; Ftime=2.920, P=0.035), and the subjective symptom scores of diclofenac sodium group were significantly lower than those of bromofenac sodium group (all at P<0.05).The preoperative, 1-week postoperative, 6-week postoperative tear secretion volume were (5.87±2.37), (6.07±2.53), and (6.29±0.25) mm in diclofenac sodium group, and (7.36±2.74), (6.29±3.46), and (5.80±2.76) mm in bromofenac sodium group.There was statistically significant difference in the tear secretion volume between the two groups before surgery ( F=6.910, P=0.012), but there was no significant difference on postoperative weeks 1 and 6 ( F=1.121, 0.772; P=0.729, 0.384).The preoperative, 1-week postoperative, 6-week postoperative non-invasive tear break-up time (NIBUT) were (8.00±6.28), (6.68±5.24), and (6.17±5.00) seconds in diclofenac sodium group, and (6.40±5.28), (4.50±2.46), and (5.39±5.39) seconds in bromofenac sodium group.There was no significant difference in NIBUT between the two groups ( Fgroup=3.415, P=0.068).There was significant difference in NIBUT within groups among different time points ( Ftime=4.358, P=0.020).The 1-day postoperative, 1-week postoperative, 6-week postoperative corneal epithelial staining score were (1.40±0.81), (0.13±0.34), (0.00±0.00) points in diclofenac sodium group, and (1.38±0.89), (0.22±0.47), and (0.00±0.00) points in bromofenac sodium group.There was no statistically significant difference in the corneal epithelial staining score between the two groups after surgery ( Fgroup=0.110, P=0.741).There were statistically significant differences in corneal epithelial staining scores within groups among different time points ( Ftime=175.054, P<0.01).The 1-day postoperative, 1-week postoperative, 6-week postoperative anterior chamber flare classification were 1.13±0.51, 0.13±0.34, and 0.00±0.00 in diclofenac sodium group, and 1.02±0.34, 0.16±0.37, and 0.00±0.00 in bromofenac sodium group.There was no significant difference in the overall anterior chamber flash between the two groups ( Fgroup=0.045, P=0.507).There were statistically significant differences in anterior chamber flash within groups among different time points ( Ftime=322.331, P<0.001).There was no significant difference in the preoperative and 6-week postoperative macular fovea thickness between both groups ( t=-0.221, -0.374; both at P>0.05).The incidence of macular cystoid edema 6 weeks after operation was 0% in both groups.Subjects tolerated the two tested drugs well.Eight adverse events occurred in this study, all of which were mild postoperative IOP elevation, including 3 in diclofenac sodium group with an incidence of 6.67% and 5 in bromofenac group with an incidence of 11.1%.IOP returned to normal in all the patients 1 week after stopping the use of drug. Conclusions:Two nonsteroidal anti-inflammatory drugs are safe and effective for anti-inflammatory treatment after cataract phacoemulsification combined with IOL implantation.The new diclofenac sodium eye drops are more comfortable than bromfenac sodium eye drops.