Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

mRNA vaccines and drugs enter host cells through delivery vectors and produce target proteins using the protein synthesis mechanism of cells. mRNA and target proteins can induce the body to produce innate immunity and adaptive immunity, and the target protein itself can also play a corresponding role. Tumor cells are inhibited and cleared under the above immune effects and target proteins. This article reviews the immunogenicity of mRNA, that is, the specific mechanism of stimulating the body to produce an immune response.At the same time, the main types of cells transfected by mRNA vaccine were briefly introduced. (1) Muscle cells, epidermal cells, dendritic cells and macrophages at the injection site; (2) immune cells in peripheral lymphoid organs;(3) liver cells and spleen cells, etc. Although transfected with a variety of cells, it is mainly enriched in immune cells and liver cells because immune cells express toll-like receptors and liver cells express low-density lipoprotein receptors. mRNA vaccines and drugs are mainly divided into non-replicating mRNA (nrmRNA),self-amplifying RNA (saRNA), trans-amplifying RNA (taRNA) and circular RNA (circRNA).This article reviews how these 4 types of vaccines and drugs work, and compares their advantages and disadvantages. Due to its inherent immunogenicity, instability, and low delivery efficiency in vivo, mRNA vaccines and drugs have been unable to enter the clinic. This article describes in detail how to reformation and modify the 5'cap, 5'UTR, 3'UTR, ORF, 3'Poly(A) and some nucleotides of mRNA to eliminate its immunogenicity and instability. Due to the low efficiency of the delivery carrier, the researchers optimized it. This article briefly introduces the application of non-viral vectors and their targeting, specifically involving the mechanism of action of various types of delivery vectors and their advantages and disadvantages, and summarizes some of the current targeting vectors. Targeted carriers can improve the delivery efficiency of mRNA to specific tissues and prevent side effects of systemic exposure, such as liver injury. The specific methods of using mRNA vaccines and drugs to treat cancer are as follows: mRNA can be used to encode and transcribe tumor-associated antigens, tumor-specific antigens (TSAs), therapeutic antibodies, cytokines, tumor suppressors, oncolytic viruses, CRISPR-Cas9, CARs and TCRs, so as to play an anti-tumor role. In this paper, the specific mechanism of the above methods and the current research and development of corresponding mRNA vaccines and drugs are briefly reviewed. The successful development of the COVID-19 mRNA vaccine has brought mRNA technology to the attention of the world and brought new and effective means for the prevention and treatment of cancer. mRNA vaccines and drugs have the advantages of short development cycle, dual immune mechanism, safety, high efficiency and large-scale production. At the same time, there are also many areas that need further improvement, such as the development of ideal target TSAs, the in-depth development of saRNA, taRNA and circRNA, the development of targeted nano-delivery for different tissues and organs, the expansion of mRNA administration routes, and the development of mRNA that can be stably stored at room temperature or even high temperature. These problems need to be further studied and solved. In addition to cancer therapy, mRNA vaccines and drugs can also be used in the treatment of infectious diseases, genetic diseases, regenerative medicine and anti-aging. mRNA vaccines and drugs are a very promising platform, and we believe that they will benefit cancer patients in the near future.

Cognitive dysfunction is one of the serious complications of type 2 diabetes.Exercise interven-tion has a certain effect on improving diabetes cognition,but the exact process remains ambiguous.This research aims to explore the impact and molecular processes of treadmill exercises in enhancing cognitive impairments in type 2 diabetic mice.Ten m/m 8-week-old male mice were used as the control group.Forty db/db mice,each 8 weeks old and male,were categorized into four distinct groups with each group containing 10 mice,including the db/db group(model group),db+Exe group(exercise group),db+Exe+SB203580 group(exercise combined with the p38 MAPK inhibitor group),db+SB203580 group(p38 MAPK inhibitor group).db+Exe group and db+Exe+SB203580 group were subjected to treadmill running intervention(40 min/time,5 times/week,a total of 8 weeks).db+Exe+SB203580 and db+SB203580 group were intraperitoneally injected with SB203580(5 mg/kg,5 times/week,8 weeks)2 hours before treadmill exercise.The results of body weights and fasting blood glucose measurement showed that 8-week treadmill exercise could significantly reduce the body mass and fasting blood glucose levels(P＜0.01);the results of water maze showed that treadmill exercise improved cognitive dysfunction in diabetic mice(P＜0.05).Immunofluorescence staining revealed that treadmill exercise diminished the fluorescence intensity of NLRP3 in hippocampus,and there was a significant difference in CA1 and CA3 regions(P＜0.05).Treadmill exercise reduced the fluorescence intensity of PI in the hippocampus,and there was a significant difference in the DG region(P＜0.01).The results of qRT-PCR revealed that treadmill exercise decreased IL-1β and IL-18 mRNA levels in hippocampus,with a notable difference in IL-1β mRNA levels(P＜0.05).Western blotting analysis revealed that treadmill exercise reduced the concentrations of Caspase3,Caspase9 and Bax in hippocampus(P＜0.01),reduced the concentrations of TXNIP,NLRP3,GSDMD-N,IL-1β,IL-18,Cleaved Caspase1 and Caspasel(P＜0.05),decreased the levels of p-RIPK1,RIPK1,p-RIPK3 and RIPK3(P＜0.05).After adding p38 inhibitors,treadmill ex-ercise combined with p38 inhibitor intervention further inhibited the expression of Caspase3,TXNIP,GS-DMD-N and IL-18(P＜0.05),and the expression levels of Caspase9,Bax,NLRP3,IL-1β,Cleaved Caspase 1 and Caspase 1 also showed a downward trend.The expression of RIPK1 and p-RIPK3 in-creased significantly(P＜0.05),and the protein expression levels of p-p38,p-RIPK1 and RIPK3 showed an upward trend.In conclusion,treadmill running intervention can effectively improve the cogni-tive dysfunction in type 2 diabetic mice,and its mechanism is partly through the p38 MAPK signaling pathway to regulate PANoptosis.

Objective:To explore the effect of behavioral habits on the recovery of spinal cord function in patients with cervical spondylotic myelopathy after expansive open-door laminoplasty(ELAP).Methods:Retrospective analysis of clinical data of 183 patients with cervical spondylotic myelopathy who underwent ELAP at the Spinal Surgery Department of Jining Medical University Affiliated Hospital, from February 2019 to October 2022, with complete follow-up information. General clinical data of patients were collected. The patients were followed up at 3 months, 6 months and 12 months after surgery with the modified standard MacNab.The JOA score was used to evaluate the recovery of motor and sensory functions in patients before and 12 months after surgery. The recovery rate of spinal cord function was calculated based on the JOA score, and patients were divided into two groups: the group with good therapeutic effect ( n=143, recovery rate ≥ 50%) and the group with poor therapeutic effect ( n=40, recovery rate<50%). Data statistics were conducted using SPSS 20.0 software for chi-square test, rank sum test, t-test, and Logistic regression analysis. Results:There were significant differences in age ( t=-3.252, P<0.01), smoking ( χ2=21.503, P<0.01), body mass index(BMI) ( t=-5.885, P<0.01), hypertension ( χ2=20.263, P<0.01), coronary heart disease ( χ2=13.272, P<0.01), hospitalization time ( t=-2.278, P=0.02), desk and screen time ( t=-6.589, P<0.01), and frequency of rehabilitation exercise ( χ2=10.927, P<0.01) between the group with good therapeutic effect and the group with poor therapeutic effect. Further multivariate Logistic regression analysis showed that smoking ( B=2.402, OR=11.046, 95% CI=2.334-52.285, P<0.05), high BMI ( B=0.341, OR=1.406, 95% CI=1.076-1.837, P<0.05), hypertension ( B=2.238, OR=9.370, 95% CI=2.153-40.790, P<0.05), long desk and screen time ( B=0.961, OR=2.613, 95% CI=1.540-4.435, P<0.05) and low frequency of rehabilitation exercise ( B=-1.039, OR=0.354, 95% CI=0.201-0.623, P<0.05) were risk factors for spinal cord function recovery in patients with cervical spondylotic myelopathy after ELAP( P<0.05). Conclusion:Smoking, high BMI, hypertension, long desk and screen time, and low frequency of rehabilitation exercise are not adverse to the recovery of neurological function in patients with cervical spondylotic myelopathy after ELAP.

Objective: Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. Methods: Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. Results: Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1–68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9–100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3–11.6).The incidence of adverse events (any grade) was 100%, and the incidence of grade 3–4 adverse events was 54.5%. Conclusion Anlotinib combined with etoposide emerged effective for the treatment of PROC.

Objective: Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. Methods: Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. Results: Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1–68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9–100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3–11.6).The incidence of adverse events (any grade) was 100%, and the incidence of grade 3–4 adverse events was 54.5%. Conclusion Anlotinib combined with etoposide emerged effective for the treatment of PROC.

Objective: Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. Methods: Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. Results: Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1–68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9–100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3–11.6).The incidence of adverse events (any grade) was 100%, and the incidence of grade 3–4 adverse events was 54.5%. Conclusion Anlotinib combined with etoposide emerged effective for the treatment of PROC.

Humans ; Gemcitabine ; Neoplasms

Animals ; Rats ; Diabetes Mellitus ; Vascular Endothelial Growth Factor A