Innate immune system serves as the primary defense mechanism against pathogen infections,recognition of structural components of pathogens is referred to as pathogen-associated molecular patterns(PAMPs).Toll-like receptors(TLRs)are a family of transmembrane receptors that can identify PAMPs,which interact with myeloid differentiation factor 88(MyD88)and activate NF-κB dimerization,leading to the release of downstream inflammatory factors and ultimately triggering the adaptive immune system.Conse-quently,TLRs are regarded as adapters that regulate the transition from innate immunity to adaptive immunity.TLR/MyD88/NF-κB signaling pathway plays a crucial role in inflammatory diseases,infectious diseases and tumor immunity.This review article aims to explore the regulatory function of TLR/MyD88/NF-κB signaling pathway in host responses to viral,bacterial,and other microbial in-fections,providing novel insights into the immune response during the process of infection control.

ObjectiveTo explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch. (G. uralensis) and to improve the quality of cultivated G. uralensis for both medicine and food and aid in the increase in the content of effective components in G. uralensis.MethodsIn this study, whole G. uralensis plants were treated with exogenous chitosan, and comprehensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation, respectively. Effects of chitosan induction on endogenous hormones of G. uralensis were analyzed using an enzyme-linked immunosorbent assay. Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.ResultsChitosan induction significantly increased the levels of flavonoids in G. uralensis; however, the variation in triterpenoids was not substantial. Biological processes, including photosynthesis, secondary metabolism, and abiotic stress responses, were significantly enriched. Additionally, the photosynthetic pathway, photosynthesis-antenna protein pathway, and plant hormone signal transduction pathway were significantly enriched. In the flavonoid biosynthesis pathway, the upstream-related enzyme phenylalanine ammonia-lyase (PAL) and the downstream-related enzymes chalcone synthase (CHS), polyketide reductase (PKR), chalcone isomerase (CHI), and vestitone reductase (VR) were significantly upregulated.ConclusionsOur findings suggest that chitosan induction may promote the tricarboxylic acid (TCA) cycle, and the TCA cycle enhancement significantly upregulated PAL, CHS, PKR, CHI, and VR, the five key enzymes involved in flavonoid synthesis of G. uralensis, indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G. uralensis. Our findings provide a reference for improving the quality of cultivated G. uralensis from the perspective of pharmacodynamic components.

Objective:To explore the efficacy of letrozole combined with palbociclib in the treatment of hormone receptor +/human epidermal growth factor receptor-2 - (HR +/HER2 -) advanced breast cancer and its influence on serum thymidine kinase 1 (TK1) and proliferating cell nuclear antigen (Ki67) levels. Methods:A total of 82 patients with HR +/HER2 - advanced breast cancer, all admitted from Jan. 2022 to Jan. 2024 from Department of Oncology, Affiliated Hospital of Jining Medical University, were assigned to the control group ( n=41, letrozole) and the study group ( n=41, letrozole + palbociclib) according to the random number table. The therapeutic effect, tumor markers, immune function and serum TK1 and Ki67 levels were compared between the two groups. Results:The study group higher objective response rate and disease control rate than the other group [14.63% (6/41) and 85.37% (35/41) vs. 0.00% (0/41) and 58.54% (24/41) ] (Continuity correction χ2/χ2=4.50, 7.31, P<0.05). After treatment, carbohydrate antigen 153 (CA153), CA125 and carcinoembryonic antigen (CEA) in the study group were lower than the control group [ (12.17±3.19) U/mL, (23.57±3.35) U/mL and (19.51±4.13) ng/mL vs (24.37±5.25) U/mL, (35.16±5.08) U/mL, (34.28±5.72) ng/mL] ( t=12.72, 12.20, 13.41, P<0.05), serum TK1 and Ki67 levels were also lower [ (3.61±0.75) pmol/L and (7.89±1.16) ng/mL vs. (4.76±0.88) pmol/L and (10.85±1.94) ng/mL] ( t=6.37, 8.39, P<0.05). After treatment, CD3 +, CD4 +, CD4 +/CD8 + higher than the control group [ (48.64±5.88) %, (31.34±4.06) %, (1.22±0.27) vs. (43.16±6.09) %, (27.04±3.35) %, (0.87±0.35) ] ( t=4.15, 5.23, 5.07, P<0.05), while CD8 + was lower [ (25.73±4.11) % vs. (30.94±4.47) %] ( t = 5.49, P<0.05) . Conclusions:Letrozole combined with palbociclib is effective in the treatment of HR +/HER2 - advanced breast cancer and can reduce tumor markers and serum TK1 and Ki67 levels in patients.

Objective:To explore the efficacy of letrozole combined with palbociclib in the treatment of hormone receptor +/human epidermal growth factor receptor-2 - (HR +/HER2 -) advanced breast cancer and its influence on serum thymidine kinase 1 (TK1) and proliferating cell nuclear antigen (Ki67) levels. Methods:A total of 82 patients with HR +/HER2 - advanced breast cancer, all admitted from Jan. 2022 to Jan. 2024 from Department of Oncology, Affiliated Hospital of Jining Medical University, were assigned to the control group ( n=41, letrozole) and the study group ( n=41, letrozole + palbociclib) according to the random number table. The therapeutic effect, tumor markers, immune function and serum TK1 and Ki67 levels were compared between the two groups. Results:The study group higher objective response rate and disease control rate than the other group [14.63% (6/41) and 85.37% (35/41) vs. 0.00% (0/41) and 58.54% (24/41) ] (Continuity correction χ2/χ2=4.50, 7.31, P<0.05). After treatment, carbohydrate antigen 153 (CA153), CA125 and carcinoembryonic antigen (CEA) in the study group were lower than the control group [ (12.17±3.19) U/mL, (23.57±3.35) U/mL and (19.51±4.13) ng/mL vs (24.37±5.25) U/mL, (35.16±5.08) U/mL, (34.28±5.72) ng/mL] ( t=12.72, 12.20, 13.41, P<0.05), serum TK1 and Ki67 levels were also lower [ (3.61±0.75) pmol/L and (7.89±1.16) ng/mL vs. (4.76±0.88) pmol/L and (10.85±1.94) ng/mL] ( t=6.37, 8.39, P<0.05). After treatment, CD3 +, CD4 +, CD4 +/CD8 + higher than the control group [ (48.64±5.88) %, (31.34±4.06) %, (1.22±0.27) vs. (43.16±6.09) %, (27.04±3.35) %, (0.87±0.35) ] ( t=4.15, 5.23, 5.07, P<0.05), while CD8 + was lower [ (25.73±4.11) % vs. (30.94±4.47) %] ( t = 5.49, P<0.05) . Conclusions:Letrozole combined with palbociclib is effective in the treatment of HR +/HER2 - advanced breast cancer and can reduce tumor markers and serum TK1 and Ki67 levels in patients.

Innate immune system serves as the primary defense mechanism against pathogen infections,recognition of structural components of pathogens is referred to as pathogen-associated molecular patterns(PAMPs).Toll-like receptors(TLRs)are a family of transmembrane receptors that can identify PAMPs,which interact with myeloid differentiation factor 88(MyD88)and activate NF-κB dimerization,leading to the release of downstream inflammatory factors and ultimately triggering the adaptive immune system.Conse-quently,TLRs are regarded as adapters that regulate the transition from innate immunity to adaptive immunity.TLR/MyD88/NF-κB signaling pathway plays a crucial role in inflammatory diseases,infectious diseases and tumor immunity.This review article aims to explore the regulatory function of TLR/MyD88/NF-κB signaling pathway in host responses to viral,bacterial,and other microbial in-fections,providing novel insights into the immune response during the process of infection control.

Objective:To investigate the value of serum miR-145 and matrixmetallo proteinase-2 (MMP-2) levels in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy in triple-negative breast cancer.Methods:125 patients with triple-negative breast cancer who received neoadjuvant chemotherapy in the Hospital from Jan. 2022 to Dec. 2023 were prospectively included as the study objects, and 130 healthy people matching the age of the case group who underwent physical examination in our hospital during the same period were included as the healthy control group. Real-time fluorescence quantitative polymerase chain reaction was used to detect the serum miR-145 level of all subjects. Serum MMP-2 levels were determined by enzyme-linked immunosorbent assay (ELISA). After neoadjuvant chemotherapy, patients were evaluated according to Miller-Payne (MP) grading criteria and divided into pCR group and non-PCR group.Results:The serum miR-145 level in patients with tertiary breast cancer was 1.49±0.27, which was significantly lower than that in healthy control group (2.79±0.49), with statistical significance ( t=20.33, P<0.001). The serum MMP-2 level in triple negative breast cancer patients was (153.07±38.36) ng/mL, which was significantly higher than that in healthy control group (84.38±12.63) ng/mL, and the difference was statistically significant ( t=26.13, P<0.001). After neoadjuvant chemotherapy, the serum miR-145 level in non-PCR patients before treatment was 1.36±0.21, which was significantly lower than that in pCR group (1.74±0.20), with statistical significance ( t=9.93, P<0.001). After neoadjuvant chemotherapy, the serum MMP-2 level in non-PCR patients before treatment was (169.57±30.45) ng/mL, which was significantly higher than that in pCR group (121.61±31.79) ng/mL, and the difference was statistically significant ( t=8.24, P<0.001). Pearson correlation analysis showed that there was a significant negative correlation between serum miR-145 and MMP-2 levels in patients with triple-negative breast cancer before treatment ( r=-0.47, P<0.001). ROC curve analysis results showed that serum miR-145 and MMP-2 levels before treatment predicted the sensitivity and specificity of pCR after neoadjuvant chemotherapy for triple-negative breast cancer were 82.9% and 74.4%, 45.1% and 99.8%, respectively. The sensitivity and specificity of pCR after neoadjuvant chemotherapy for triple-negative breast cancer were 84.1% and 88.4%, respectively. Conclusion:Serum miR-145 and MMP-2 levels are related to the efficacy of neoadjuvant chemotherapy in patients with triple-negative breast cancer, and the combined application of the two has certain predictive value.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Acute pancreatitis is one of the most common acute abdominal diseases in clinical practice,and the common etiologies of acute pancreatitis include biliary diseases,alcohol,pancreatic duct diseases,metabolic disorders(hypertriglyceridemia and hypercalcemia),excessive eating,and diseases of the descending duodenum(periampullary duodenal diverticula).According to the etiology,acute pancreatitis is classified into biliary pancreatitis and hyperlipidemic pancreatitis,and although there are various pathogenic factors for biliary pancreatitis,biliary diseases including bile duct stones remain the most important etiology of biliary pancreatitis.Obstructed biliopancreatic duct drainage and abnormal pressure due to various causes,bile reflux into the pancreatic duct,obstruction of pancreatic juice drainage,and abnormal activation of pancreatic enzymes are the central links in the development of biliary pancreatitis.The location,size,texture,number and shape of bile duct stones are associated with the incidence rate and severity of biliary pancreatitis to a certain degree.

Alzheimer disease(AD),commonly known as senile dementia,is the most common type of dementia,resulting in progressive impairment of cognitive function,and is often accompanied by a variety of psychiatric symptoms,such as agitation.Agitated symptoms in AD patients often cause an increasing burden on caregivers,and current psychiatric medications may exacerbate adverse effects such as cognitive impairment and motor retardation in patients.Therefore,non-drug intervention is a very important adjuvant treatment option.This article reviews the clinical manifestations,possible mechanisms,drug therapy and non-drug intervention measures of agitation in order to provide reference for more effective treatment of AD.

Objective:To investigate the correlation between collateral circulation and infarct pattern and outcome in acute ischemic stroke patients with anterior circulation intracranial atherosclerosis.Methods:Acute ischemic stroke patients with anterior circulation intracranial atherosclerotic severe stenosis or occlusion admitted to the Department of Neurology, the First Affiliated Hospital of Xinxiang Medical College from September 2018 to March 2020 were included prospectively. According to diffusion-weighted imaging, the infarct patterns were divided into perforator pattern, territorial pattern, watershed pattern, and mixed pattern. At 90 d after onset, the modified Rankin Scale was used to evaluate the outcome. 0-2 was defined as good outcome, and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of clinical outcome. Results:A total of 89 patients were enrolled, 50 (56.2%) had good collateral circulation and 39 (43.8%) had poor collateral circulation. The distribution patterns of infarct: 22 patients (24.7%) were perforator pattern, 26 (29.2%) were territorial pattern, 17 (19.1%) were watershed pattern, and 24 (30.0%) were mixed pattern. The proportion of patients with good collateral circulation was 81.8%, 65.4%, 29.4% and 41.7%, respectively in the perforator pattern group, territorial pattern group, watershed pattern group, and mixed pattern group. Good collateral circulation was more common in the perforator pattern group, and poor collateral circulation was more common in the watershed pattern group. At 90 d after onset, 53 patients (59.6%) had a good outcome and 36 (40.4%) had a poor outcome. The baseline homocysteine level in the good outcome group was significantly lower than that in the poor outcome group (17.91±4.62 μmol/L vs. 20.35±4.67 μmol/L; t=2.436, P=0.017), and the proportion of patients with good collateral circulation was significantly higher than that of patients with poor outcome (73.6% vs. 30.6%; χ2=16.124, P<0.001). Multivariate logistic regression analysis showed that higher homocysteine level was an independent risk factor for poor outcome (odds ratio 1.174, 95% confidence interval 1.061-1.298; P=0.002) and good collateral circulation was an independent protective factor for good outcome (odds ratio 0.095, 95% confidence interval 0.038-0.239; P<0.001). Conclusions:Good collateral circulation was more common in patients with perforator pattern, and poor collateral circulation was more common in patients with watershed pattern. Good collateral circulation was independently associated with the good clinical outcome in acute ischemic stroke patients with anterior circulation intracranial atherosclerosis.