With the accelerating aging of world population, the prevalence and disease burden of dementia such as Alzheimer's disease is increasing annually. As one of the major risk factors for dementia, air pollution is still an urgent global concern. Studies on the association between ambient particulate matter (PM), one of the major air pollutants, and dementia, such as Alzheimer's disease, are gaining attention. This paper reviewed the current evidence of relevant epidemiological and toxicological studies to illustrate the possible mechanisms underlying the effects of PM exposure on Alzheimer's disease through inflammatory responses, oxidative stress, endocrine disruption, excitatory neurotoxicity, glial cell activation, and intestinal flora disruption, which may provide clues for mitigating the health risks of air pollution and preventing Alzheimer's disease.

Bacterial reinfection in the lungs of patients with influenza virus(IV)is a key factor leading to serious illness and death.The adverse consequences caused by co-infection with IV and Streptococcus pneumoniae(SPN)impose a serious burden on patients.However,the specific pathogenesis is complex,how to make better use of the mouse animal model of IV/SPN co-infection for subsequent basic research is of great significance.This article reviews the selection of animals,the selection of pathogen types,the selection of different modeling times,the identification of the co-infection model,and its applications in the IV/SPN co-infection model,so as to provide a reference for the selection of animal models of IV/SPN co-infection in the future.

A 40-year-old male patient was treated orally with carbamazepine 0.1 g once daily for epilepsy. Twenty days later, the patient developed fever without obvious cause (highest body temperature 39.0 ℃), which showed no improvement after treatments with ribavirin and ibuprofen. Eleven days later, splenomegaly occurred, and serum ferritin was elevated (1 188.18 μg/L). Etiological testing showed positive influenza virus A/B antibody but negative nucleic acid; tests of Epstein-Barr virus, cytomegalovirus, novel coronavirus, respiratory syncytial virus, adenovirus, human rhinovirus, Mycoplasma pneumoniae, Mycobacterium tuberculosis, Leishmania donovani, Brucella, and Toxoplasma gondii all showed negative results. Blood culture and autoantibody profile were both negative. Anti-infective treatments with ceftizoxime, levofloxacin, ganciclovir, and oseltamivir were successively given. Oseltamivir was later changed to peramivir. Eight days later, the patient′s body temperature fluctuated between 38.4 ℃ and 38.6 ℃. Fibrinogen decreased to 1.49 g/L, serum ferritin increased to 1 218.91 μg/L, and soluble CD25 increased to 3 814 kU/L. Bone marrow smear showed hemophagocytosis. Secondary hemophagocytic lymphohistiocytosis was diagnosed, which was considered to be caused by carbamazepine. Carbamazepine and the aforementioned anti-infective drugs were discontinued, and intravenous infusion of dexamethasone 15 mg once daily was administered. The patient′s body temperature decreased to 37.5 ℃. Six days later, intravenous infusion of etoposide 100 mg once was added. The next day, the patient no longer had fever, and laboratory indicators showed significant improvement. The patient′s laboratory indicators returned to normal in re-examination 3 months later.

Bacterial reinfection in the lungs of patients with influenza virus(IV)is a key factor leading to serious illness and death.The adverse consequences caused by co-infection with IV and Streptococcus pneumoniae(SPN)impose a serious burden on patients.However,the specific pathogenesis is complex,how to make better use of the mouse animal model of IV/SPN co-infection for subsequent basic research is of great significance.This article reviews the selection of animals,the selection of pathogen types,the selection of different modeling times,the identification of the co-infection model,and its applications in the IV/SPN co-infection model,so as to provide a reference for the selection of animal models of IV/SPN co-infection in the future.

A 40-year-old male patient was treated orally with carbamazepine 0.1 g once daily for epilepsy. Twenty days later, the patient developed fever without obvious cause (highest body temperature 39.0 ℃), which showed no improvement after treatments with ribavirin and ibuprofen. Eleven days later, splenomegaly occurred, and serum ferritin was elevated (1 188.18 μg/L). Etiological testing showed positive influenza virus A/B antibody but negative nucleic acid; tests of Epstein-Barr virus, cytomegalovirus, novel coronavirus, respiratory syncytial virus, adenovirus, human rhinovirus, Mycoplasma pneumoniae, Mycobacterium tuberculosis, Leishmania donovani, Brucella, and Toxoplasma gondii all showed negative results. Blood culture and autoantibody profile were both negative. Anti-infective treatments with ceftizoxime, levofloxacin, ganciclovir, and oseltamivir were successively given. Oseltamivir was later changed to peramivir. Eight days later, the patient′s body temperature fluctuated between 38.4 ℃ and 38.6 ℃. Fibrinogen decreased to 1.49 g/L, serum ferritin increased to 1 218.91 μg/L, and soluble CD25 increased to 3 814 kU/L. Bone marrow smear showed hemophagocytosis. Secondary hemophagocytic lymphohistiocytosis was diagnosed, which was considered to be caused by carbamazepine. Carbamazepine and the aforementioned anti-infective drugs were discontinued, and intravenous infusion of dexamethasone 15 mg once daily was administered. The patient′s body temperature decreased to 37.5 ℃. Six days later, intravenous infusion of etoposide 100 mg once was added. The next day, the patient no longer had fever, and laboratory indicators showed significant improvement. The patient′s laboratory indicators returned to normal in re-examination 3 months later.

Objective:To detect the expression of Toll-like receptor 7(TLR7)in blood neutrophils of patients with allergic rhi-nitis(AR),allergic asthma(AA)and allergic rhinitis combined with allergic asthma(ARA)before and after allergen challenge.Methods:A total of 44 AR,36 AA,19 ARA patients and 19 healthy control(HC)were recruited,the extracts of Artemisia siever-siana wild allergen(ASWE),house dust mite allergen(HDME)and Platanus pollen allergen(PPAE)were used to challenge periph-eral blood of HC as well as the patients,the expression of TLR7 in neutrophils was detected by flow cytometry.Results:In a resting state,compared with HC,upregulated expression of TLR7 in neutrophils in patients with airway allergy:the percentage of TLR7+neu-trophils in AR,AA,ARA patients increased 6 times,3.18 times and 6.15 times,respectively,and the mean fluorescence intensity(MFI)of TLR7 expression in neutrophil in ARA was enhanced by 24%.The results of allergen challenge tests showed that the expres-sion of neutrophils TLR7 did not change in HC subjects after the allergen challenge,whereas the expression of TLR7 in neutrophils of patients with airway allergy was upregulated after the allergens challenge.After HDME and PPAE challenge,the percentage of TLR7+neutrophils in peripheral of AR patients increased by 8.40%and 33.03%,respectively,and the MFI of TLR7 enhanced by 29.62%and 35.72%,respectively.After ASWE and PPAE challenge.The percentage of TLR7+neutrophils in peripheral of AA pa-tients increased by 59.18%and 1.06 times,respectively,and the MFI of TLR7 enhanced by 68.93%and 47.33%,respectively.How-ever,after HDME stimulation only enhanced the MFI of neutrophil TLR7 in AA patients by 66.14%;after HDME challenge,the per-centage of TLR7 and MFI in peripheral blood neutrophils of patients with ARA increased by 21.05%and 35.61%,respectively,while after PPAE challenge,the percentage of TLR7+cells in patients with ARA increased by 20.07%.Conclusion:The expression of TLR7 in blood neutrophils is increased in patients with allergic airway diseases after allergen stimulation,suggesting that allergens may be involved in the occurrence and development of allergic airway diseases by inducing TLR7 expression changes in neutrophils.

Oral frailty and cognitive impairment are the common geriatric syndromes.There may be similar correlation mechanism between them,which are related with polypharmacy,malnutrition,inflammato-ry responses and psychosocial factors.The occurrence of oral frailty could potentially increase the risk of cog-nitive impairments,in which tooth loss,reduced chewing function,swallowing difficulties,low tongue pres-sure,and diminished oral motor function are closely correlated with cognitive impairments.Understanding the correlation between the two is conducive to prevent and interfere the healthy status in elderly people,thus in-crease their quality of life and health level.

Background Cooking oil fumes are closely related to immune response, and adipose tissue also plays an important role in immune regulation. At present, the biological effect and mechanism of inflammation of adipose tissue induced by oil fume exposure are not clear yet. Objective To investigate the inflammatory effect of different exposure duration of cooking fumes on adipose tissue in mice and explore the role of Nod-like receptor pyrin domain 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase 1)/interleukin (IL)-1β signaling pathway. Methods Forty 8-week-old female C57BL/6J mice were randomly divided into 3-day control group (CON₃ group), 7-day control group (CON₇ group), 3-day oil fume exposure group (COF₃ group), and 7-day oil fume exposure group (COF₇ group), with 10 mice in each group. The mice were exposed to oil fumes in a cooking oil fume formation and exposure equipment (COFFEE) for 20 min, followed by a 10-min pause, 1 h a day for consecutive 3 d or 7 d. General condition of mice was observed and body weight was measured every day. After exposure, blood was sampled from the eyeball. Serum levels of IL-6, IL-27, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The adipose tissue of mice was collected and observed after hematoxylin-eosin (HE) staining. The percentages of CD4⁺ and CD8⁺T cells in adipose tissue were detected by flow cytometry. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of nuclear factor-κB (NF-κB), NLRP3, Caspase 1, and IL-1β in adipose tissue. Western blot was used to detect the expression levels of NLRP3, Caspase 1, and IL-1β in adipose. Results Compared with the corresponding control group, serum IL-6, IL-27, and IL-1β contents in the COF₃ group and the COF₇ group were significantly increased (P<0.05) except IL-6 in the COF₃ group, and the levels in the COF₇ group were significantly higher than those in the COF₃ group (P<0.05). Vacuolar lipid droplets in adipocytes decreased, cytoplasm shrank, and inflammatory cells infiltrated in the COF₇ group after HE staining. The flow cytometry results showed that the proportions of CD4⁺ and CD8⁺T cells in adipocytes of the COF₃ group and the COF₇ group were increased compared to the corresponding control group, with a significant increase in the COF₇ group (P<0.05), and the CD4⁺/CD8⁺T ratio also significantly increased progressively in the two groups (P<0.05). The results of RT-qPCR showed that compared with the corresponding control group, the mRNA expression levels of NF-κB, NLRP3, Caspase 1, and IL-1β in adipose tissue of mice in the COF₃ group and the COF₇ group were significantly increased (P<0.05, P<0.01). The mRNA expression levels of mice in each exposure group gradually increased over time. The Western blot results showed that compared with the corresponding control group, the protein expressions of NLRP3 and Caspase 1 in the COF₃ group were significantly increased (P<0.01), and the expression of IL-1β protein also increased but without statistical significance. The protein expressions of NLRP3, Caspase 1, and IL-1β in the COF₇ group were significantly higher than those in the CON₇ group (P<0.05, P<0.01). Conclusion Acute exposure to cooking oil fumes can induce significant inflammatory response in adipose tissue, and the effect gradually increases with the extension of exposure time. The mechanism of action may be related to the activation of NLRP3 inflammasome signaling pathway.

Background It is unclear if there is any combined effect of air pollutants and non-optimal temperature on metabolic syndrome, or any molecular mechanisms of related signaling pathways in the process, which requires urgent systematic research. Objective To observe the effects of combined exposure to PM_2.5 and non-optimal temperature on metabolic damage at gene and protein levels in mice, and elucidate the role of related signaling pathway in crucial organs. Methods A total of 60 six-week-old male C57BL/6J mice were randomly divided into six groups: a normal temperature-filter air group (T_N-FA), a normal temperature-concentrated PM_2.5 group (T_N-PM), a heat-filter air group (T_H-FA), a heat-concentrated PM_2.5 group (T_H-PM), a cold-filter air group (T_C-FA), and a cold-concentrated PM_2.5 group (T_C-PM). The Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) was used to provide combined exposure settings of air types [concentrated PM_2.5 and filter air (FA)] and temperatures [normal (22°C), cold (4°C), and heat (30°C)] for 4 weeks. Skeletal muscle and white adipose tissue (WAT) of the mice were sampled at the end of exposure, and transcriptomics and Western blot (WB) assay were adopted to observe selected gene and protein expression levels in the samples respectively. Results The transcriptomics results indicated that the PM_2.5 exposure enhanced the number of differentially expressed genes. Specifically, 4820 genes were differentially expressed in the T_N-PM mice compared to the T_N-FA mice at normal temperature, and 1143 genes were differentially expressed in the Tc-PM mice compared to the Tc-FA mice in the cold environment. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and the endoplasmic reticulum protein processing pathway were identified as the most significant pathways in metabolic injury resulting from combined exposure to PM_2.5 and non-optimal temperature exposure. The WB results showed that exposure to PM_2.5 in the normal temperature and the cold environments led to a significant increase in the expression of p-AKT in WAT (P<0.01, P<0.05) and a significant decrease in the expression of GLUT4 (P<0.05, P<0.01). In skeletal muscle, exposure to PM_2.5 led to a significant decrease in GLUT4 (P<0.05) in all environments, with a consistent trend of change as observed in WAT. Conclusion Cold/heat exposure might promote PM_2.5-induced metabolic disorder through suppression of the AKT/GLUT4 pathway, aggravating metabolic damage.

Background:Ulcerative colitis(UC)is a chronic non-specific disease with potential for disability,and clinical treatment mainly relies on drugs.Currently,small molecule drugs(SMDs)have shown good application prospects.Aims:To evaluate the efficacy and safety of SMDs in the treatment of UC.Methods:Randomized controlled trials(RCTs)of SMDs in treatment of moderate-to-severe UC from CNKI,Wanfang Data,VIP,China Biomedical Literature Database,PubMed,Cochrane Library and Embase were searched from the establishment of the database to March 2024.References were screened and data extracted according to inclusion and exclusion criteria,and meta-analysis was performed using RevMan 5.3 software.Results:A total of 16 literatures involving 22 RCTs were finally included.Meta-analysis results suggested that SMDs had better efficacy indicators than placebo,such as clinical response rate(RR=1.86,95%CI:1.60-2.16,P<0.000 01),clinical remission rate(RR=3.01,95%CI:2.17-4.16,P<0.000 01),mucosal healing rate(RR=2.93,95%CI:2.27-3.79,P<0.000 01)and maintained response rate(RR=3.87,95%CI:3.11-4.81,P<0.000 01)were improved,and there was a statistical difference between them.And in terms of safety,SMDs compared to placebos,The incidence of adverse reactions(RR=1.02,95%CI:0.96-1.08,P=0.55),the incidence of serious adverse reactions(RR=0.77,95%CI:0.59-1.00,P=0.05),and the incidence of adverse reactions leading to drug withdrawal(RR=0.78,95%CI:0.59-1.02,P=0.07)were not statistically significant.Conclusions:SMDs are effective and safe in UC patients,which provides a new idea for the treatment of UC.