The platelets play the important role in tumor angiogenesis, growth, and metastasis, in addition to coagulation. The interaction between tumors and platelets can produce "tumor-induced platelets", which leads various changes of platelet characteristics. In addition, activated platelets can also inhibit the effects of both chemotherapy and immunotherapy, therefore, both inhibiting platelet activation and depleting platelets can effectively improve tumor prognosis. In this review, we introduced the key role of platelets in the development of tumors, summarized their application in tumor diagnosis, monitoring, and treatment, and provided our view on how to develop precise delivery strategies based on platelets for achieve efficient and safe tumor treatment.

The immunosuppressive tumor microenvironment significantly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs), the most abundant immune cells in the tumor microenvironment, often exhibit an immunosuppressive M2 phenotype, contributing to this immunosuppressive landscape. Modulating TAMs to adopt anti-tumor phenotypes can enhance immunotherapy outcomes and inhibit tumor progression.In recent years, tumor immunotherapy leveraging engineered bacteria has garnered considerable attention. Bacteria possess the ability to target tumors, preferentially colonizing tumor regions, and contain abundant pathogen-associated molecular patterns that effectively activate TAMs within the immunosuppressive tumor environment. This activation enhances the tumoricidal and clearance capabilities of TAMs. With the rapid advancements in synthetic biology, engineered bacteria have emerged as a potent therapeutic modality for immunotherapy, leading to increased focus on the regulation of TAMs by engineered bacteria.This paper first outlines clinical studies on targeted TAMs therapy and engineered bacteria-based tumor therapy. It then reviews recent advancements in bacterial regulation of TAMs, detailing how engineered bacteria enhance TAM recruitment, improve TAM phagocytosis, and remodel TAM phenotypes. Modulating TAMs with engineered bacteria presents a promising therapeutic strategy and introduces a novel approach in tumor immunotherapy.

Inflammatory lung diseases are currently a major challenge threatening human health and life. Imbalanced inflammation and excessive inflammation can lead to tissue damage and trigger the occurrence and development of systemic diseases. Anti-inflammatory treatment is of vital importance for improving patient survival and quality of life. In recent years, significant progress has been made in the exploration and research of drug targeting strategies, effectively addressing issues such as slow onset, low bioavailability, and rapid in vivo clearance rates during drug delivery. Drug targeting can increase local drug concentrations, reduce dosing frequency, and mitigate side effects. This review primarily elaborates on the classification and characteristics of inflammatory lung diseases. It comprehensively reviews targeted drug delivery strategies for inflammatory lung diseases from three perspectives: local targeting, passive targeting, and active targeting. Furthermore, it discusses the prospects and challenges of drug targeted therapy for lung diseases, potentially providing new research and application ideas for the targeted treatment of inflammatory lung diseases.

Poorly differentiated and advanced thyroid cancers are characterized by high malignancy, progress rapidly, and resistance to radiotherapy and chemotherapy. These characteristics pose significant challenges, severely limiting effective treatment options. Various kinase inhibitors have been used in the treatment of refractory thyroid cancer were used accompanying by the carcinogenic mechanisms' studies investigating in thyroid cancer, such as Dabrafenib (BRAF inhibitor), Trametinib (MEK inhibitor), Vandetanib (RET inhibitor), Lenvatinib (VEGF inhibitor), and multi-target kinase inhibitors. However, drug resistance remains an inevitable issue, significantly limiting the efficacy and application of kinase inhibitors. Therapeutic approaches such as immunotherapy, redifferentiation strategies for thyroid cancer, radiopharmaceutical conjugates, and the application of nanotechnology are currently in the clinical research stage, requiring further clarification of their efficacy. Comprehensive understanding of therapeutic strategies and available treatment combinations for refractory thyroid cancer is of paramount importance in the diagnosis and treatment of thyroid cancer. Therefore, this article reviews technologies and methods for treating refractory thyroid cancer, focusing on chemotherapy, molecular targeted therapy, immunotherapy, and radiopharmaceutical therapy, aiming to provide a reference for selecting treatment strategies for refractory thyroid cancer.

AIM: To explore the mechanism of berberine on breast cancer cells based on network pharmacology and in vitro cell experiments. METHODS: Firstly, berberine and breast cancer were taken as the research objects, the intersection targets of the two were screened by VEEN diagram, GO function and KEGG enrichment analysis were performed by R language, and molecular docking and visualization were carried out by Autodock Vina and Pymol software. Then, berberine treated breast cancer MCF-7 cells for 24 h, and then in vitro cell experiments were performed. CCK-8 was used to detect cell viability, Edu and plate cloning were used to detect cell proliferation and cloning, and apoptosis was detected by An-nexin V-FITC/PI double staining and Western blot. Laser confocal and CETSA were used to verify the binding effect of berberine and AKT1 protein. RESULTS: The results of network pharmacology showed that berberine had a good binding to the core targets AKT1, AKT2 and MAPK3. Berberine (20, 40, 80 μmol/L) significantly inhibited the proliferation and cloning ability of MCF-7 cells in a concentration-dependent manner (P<0.05, P<0.01). The results of laser confocal and CETSA experiments showed that berberine and AKT1 had a binding effect, and the stability of the two was enhanced after the combination. CONCLUSION: Berberine inhibits MCF-7 cell proliferation and induces apoptosis in human breast cancer cells by targeting binding to AKT1 protein.

AIM: To explore the way and mechanism of cell death induced by Fructus Akebiae in non-small cell lung cancer (NSCLC) cells. METHODS: CCK-8, Hochest33342/PI staining, and colony formation experiments were used to detect cell viability and proliferation. Western blot was used to detect the expression of cell death-related proteins ATG5, HMGB1, GPX4, apoptosis-related proteins, and PI3K-Akt signaling pathway-related proteins. Flow cytometry was used to detect the apoptosis rate. DCFH-DA fluorescent probes were used to detect the levels of total intracellular ROS under a fluorescence microscope. RESULTS: Fructus Akebiae significantly inhibited the cell viability and proliferation of human NSCLC cells (P<0.05). The expression of apoptosis-related proteins BAX, Cleaved caspase3, and Cleaved caspase9 in NSCLC cells was significantly increased (P<0.05), while p-PI3K, p-Akt, and BCL2 were markedly decreased (P<0.05). Fructus Akebiae was found to clearly increase the apoptosis rate and the levels of total intracellular ROS (P<0.05). The antioxidant NAC significantly reversed apoptosis, ROS production and regulation of PI3K-Akt pathway related proteins induced by Fructus Akebiae (P<0.05). CONCLUSION: Fructus Akebiae induces apoptosis via regulating ROS-mediated PI3K-Akt signaling pathway in non-small cell lung cancer cells.

AIM: To investigate the antiviral efficacy and mechanism of Qingre Xiaoyanning (QRXYN) in vivo, and provide experimental basis for their prevention and treatment of influenza A virus. METHODS: We constructed a mouse model infected with influenza A H3N2 virus. To evaluate the therapeutic effect of QRXYN on influenza A virus, we measured the body weight changes, pathological changes in lung tissue, hemagglutination titer, and viral load in mouse. To evaluate the possible mechanism of QRXYN's anti influenza A virus infection, we used the ELISA to measure the levels of TNF-α, IL-1β, IL-4, IFN-γ, and vascular cell adhesion molecule-1 (VCAM-1) in mouse bronchoalveolar lavage fluid; used flow cytometry to assess the proportions of macrophages (F4/80), helper T lymphocytes (CD4+ T lymphocytes), and natural killer (NK) cells in lung tissue; and used Western blotting to detect the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MYD88), inhibitor of kappa B kinase-β (IKK-β), NF-kappa-B inhibitor alpha (IκBα), and phospho-IKB alpha (p-IκBα) in lung tissue. RESULTS: Compared to the model group, both Oseltamivir and QRXYN can alleviate the severity of lung tissue lesions in mice, decrease the blood coagulation titer and viral load of mouse lung tissue (P<0.01), lower the levels of TNF-α, IL-4, and VCAM-1 in bronchoalveolar lavage fluid (P<0.05, P<0.01), reduce the proportion of macrophages (P<0.05, P<0.01), and increase the proportion of CD4+T lymphocytes and NK cells (P<0.05, P<0.01). Additionally, oseltamivir can reduce the expression of MYD88 protein in mouse lungs (P<0.05), while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs (P<0.05). CONCLUSION: QRXYN have good in vivo antiviral effects against the influenza A virus, and their mechanism may be related to the regulation of the immunologic function and NF-κB signal pathway.

AIM: To research the regulatory effects of Butein on lipid deposition and inflammation in non-alcoholic steatohepatitis (NASH). METHODS: HepG2 cells were divided into solvent control group (1‰ dimethyl sulfoxide) and different concentration of Butein groups (1, 3, 6, 12, 25, 50 μmol/L). The survival rate of HepG2 cells were detected, the low and high concentration groups of butein were determined. HepG2 cells were divided into solvent control group (1‰ DMSO), model group (induction with 1 mmol/L free fatty acids in vitro), low and high concentration of Butein groups. After 24 hours’ cell culture in each group, expression of triglyceride (TG), lipid synthesis-related factors SREBP-1c, FAS, SCD-1, lipid oxidation-related factors PPARα, CPT1A, MLYCD, and inflammatory factors TNF-α and MCP-1 in each group were detected. The model of NASH was constructed on C57BL/6J mouse by methionine choline deficiency diet (MCD). Normal diet group (ND group), model group (MCD group), low dose (100 mg·kg-1·d-1) and high dose (200 mg·kg-1·d-1) of Butein groups were established. After 4 weeks of feeding, pathological changes of liver tissues in each group were observed, contents of liver and serum TG and TC in each group were detected, and protein expression levels of lipid synthesis-related factors SREBP-1c, FAS, SCD-1 and lipid oxidation-related factors PPARα, CPT1A,  ACOX1 and MLYCD, inflammatory factors TNF-α and MCP-1in liver tissues were detected. RESULTS: Compared with solvent control group, Butein inhibited HepG2 cell growth when the concentration was ≥12 μmol/L (P<0.05). Make 5 and 10 μmol/L as low and high concentration groups, respectively. Compared with the solvent control group, the intracellular TG content of HepG2 cells in butein group was significantly lower (P<0.05). Compared with the model group, mRNA expressions of SREBP-1c, FAS, and SCD-1 was significantly lower (P<0.05), while mRNA expression of PPARα, CPT1A, and MLYCD was significantly higher (P<0.05), mRNA expression of TNF-α, MCP-1 was significantly decreased (P<0.05) in high-concentration butein group. Compared with the model group, the expression of SREBP-1c, FAS, SCD-1, MCP-1, TNF-α protein decreased and the expression of PPARα, CPT1A, MLYCD protein increased in the high concentration group. Compared with ND group, liver histological sections of MCD group showed obvious fat accumulation and inflammatory cell infiltration. Compared with the MCD group, the pathological manifestations of fat accumulation and inflammatory cell infiltration in the liver tissue of the butein groups were significantly improved, and the contents of TG and TC in the liver tissue of the butein groups were significantly decreased (P<0.05), while the protein expressions of PPARα, CPT1A, ACOX1, MLYCD were increased, and the protein expressions of SREBP-1c, FAS, SCD-1, TNF-α and MCP-1 were decreased in butein groups. CONCLUSION: Butein can improve lipid deposition and inflammation in NASH livers. Its mechanism may be to reduce the expression of lipid synthesis-related factors, enhance the expression of lipid oxidation-related factors, and reduce the expression level of inflammatory factors.

AIM: To investigate the involvement of HIF-1α/VEGF regulation in its anti-angiogenesis effects using adjuvant-induced arthritis (AIA) rats. METHODS: AIA rats were orally treated by QLY extract for 24 days. After sacrifice, the joints were subjected to histological examination, while the blood was used in ELISA or biochemical tests. In addition, HUVEC cells were treated by QLY in vitro. MTT, wound-healing and tube-formation experiments were then  performed. Expression of some relevant proteins in cells were investigated.RESULTS: Compared to the healthy controls, obvious synovial invasion and angiogenesis occurred in AIA rats. Blood levels of HIF-1ɑ, VEGF, PDGF, and TGF-β1 were increased, while the ratio of MDA/SOD was decreased a lot. After QLY treatment, all these abnormalities were attenuated. In vitro experiments, QLY showed notable potentials in inhibiting proliferation, migration and tube-constructing abilities of HUVEC cells. Furthermore, it suppressed the expression of p-MEK/MEK and p-ERK/ERK. CONCLUSION: QLY can reduce the pathological functions of vascular endothelial cells by inhibiting HIF-1α/VEGF, and it consequently eased AIA-related abnormal angiogenesis in AIA rats' joints.

AIM: To examine the impact of the transcription factor 7 analogue 2 (TCF7L2) gene polymorphism on the hypoglycaemic effect of exenatide in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 100 newly diagnosed Han Chinese patients with T2DM who had not received any drug treatment were selected from the Affiliated Hospital of Xuzhou Medical University and treated with exenatide monotherapy for 6 months. The TCF7L2 rs290487 was genotyped by SnaPshot method, and blood glucose levels, lipids profiles and pancreatic function evaluation indicators were measured at baseline, 3 months and 6 months after exenatide treatment. Multiple linear regression analysis was employed to assess the correlation between each indicator and the reduction in glycated hemoglobin (HbA1c) levels after 6 months of exenatide treatment. The expression of TCF7L2 protein in the plasma of T2DM patients was detected by enzyme-linked immunosorbent assay (ELISA) kit. Furthermore, western blotting was conducted to ascertain TCF7L2 expression in pancreatic tissues obtained from db/db mice and INS-1 cells cultured under high glucose conditions. Lentivirus transfection was used to overexpress or knock down TCF7L2 in insulinoma cell line (INS-1) cells, followed by measurement of KSIS activity and insulin content after a 24-hour intervention with exenatide. RESULTS: The distribution pattern of TCF7L2 rs290487 was found to be in accordance with Hardy-Weinberg equilibrium (P>0.05). Following 6 months of exenatide treatment, there was a notable reduction in blood glucose levels and an improvement in lipid profiles when compared to baseline values. Additionally, there was a significant increase in the homeostasis model assessment of beta-cell function (HOMA-B) values. Patients with the TT genotype exhibited significantly lower postprandial plasma glucose (PPG) levels and HbA1c values compared to those with the CC or CT genotypes (P<0.05). After adjusting for age, gender, body mass index (BMI), and waist to hip ratio (WHR) in the multiple linear regression model, a significant association was observed between the rs290487 TT genotype, baseline HbA1c levels, and family history of diabetes with the reduction in HbA1c after six months of exenatide treatment (P<0.05). Furthermore, individuals with the rs290487 TT genotype demonstrated a notable elevation in TCF7L2 expression in plasma among T2DM patients in comparison to those with the CC genotype (P<0.05). In particular, pancreatic tissue from db/db mice exhibited markedly elevated TCF7L2 expression compared to [db/][m] mice. However, this up-regulation was reversed by exenatide treatment. Similarly, INS-1 cells cultured under high glucose conditions demonstrated an increase in TCF7L2 expression, which was ameliorated upon exenatide administration. The knockdown of TCF7L2 using shRNA enhanced the KSIS function of pancreatic β cells and augmented the insulinotropic effect of exenatide. Conversely, the upregulation of TCF7L2 impaired the KSIS function of pancreatic β cells and attenuated the insulinotropic effect of exenatide. CONCLUSION: The TCF7L2 rs290487 gene polymorphism is closely associated with the hypoglycaemic efficacy of exenatide therapy. The risk allele C may diminish the effectiveness of exenatide by impacting the levels of PPG and HbA1c in T2DM patients. The mutation at TCF7L2 rs290487 site (C→T) influenced the expression of TCF7L2 protein. By exerting its regulatory effect, exenatide may be capable of regulating the impact of TCF7L2 on the function of pancreatic β cells.

AIM: To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of two recombinant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection. METHODS: We conducted a randomized, open-label, single dose, two period, crossover study. A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses (0.2 U/kg) of the investigational products every period. The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing. RESULTS: Euglycemic clamp technique was successfully established. C-peptide levels detected at each time point before and after administration indicated that endogenous insulin secretion was inhibited in the two groups after administration. The geometric mean ratio of Cmax and AUC0-t and 90% confidence interval (CI) of test preparation and reference preparation under fasting condition were in the range of 80.00%-125.00%. CONCLUSION: The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

AIM: To investigate the efficacy and safety of checkpoint inhibitor lenvatinib combined with Tirelizumab in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was performed on 52 patients with advanced HCC treated with Renvatinib, tirellizumab or their combination from January 2021 to December 2022 in Zhongda Hospital Affiliated to Southeast University, with disease progression, death and intolerance as endpoints. Efficacy was assessed according to RECIST 1.1 criteria and follow-up was conducted up to June 2023. The main endpoints of the study were objective response rate (ORR), disease control rate (DCR), progression-free survival, PFS) and security. RESULTS: The combination therapy significantly improved ORR and mPFS in patients compared with tirelizumab or lenvatinib monotherapy. Compared with single tirellizumab or lenvastinib, there was no significant difference in the adverse reactions associated with the combination treatment, suggesting that the combination of the two was generally well tolerated and the side effects are controllable. CONCLUSION: Lonvastinib combined with tirelizumab is more effective in the treatment of HCC, can significantly prolong PFS, and is generally well tolerated, which may be a potential treatment for advanced HCC.

AIM: To investigate the clinical effects of tirofiban and butylphthalide combined with stent thrombectomy in the treatment of patients with acute cerebral infarction in the ultra-time window. METHODS: A total of 100 patients with ACI beyond time window admitted to our hospital from January 2021 to January 2023 were randomly grouped into the control group (50 cases, treated with stent thrombectomy) and the study group (50 cases, treated with tirofiban and butylphthalide combined with stent thrombectomy), clinical data of patients were collected, and the clinical efficacy, blood lipid levels, coagulation function, neurological function, quality of life, and incidence of adverse reactions were compared between the two groups. RESULTS: Compared with the control group, the total effective rate of the study group obviously increased (P<0.05). Before treatment, there was no obvious difference between the two groups in triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), fibrinogen (FIB), NIHSS score and Barthel index scale (BI) score of patients with ACI beyond time window (P>0.05). After treatment, the TG, TC, LDL-C, FIB, D-D, and NIHSS score of ACI patients in both groups decreased (P<0.05), while HDL-C, PT, APTT, and BI score increased (P<0.05), and the above indicators improved more obviously in the study group (P<0.05). There was no obvious difference in the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSION: The combination of tirofiban and butylphthalide with stent thrombectomy in the treating ACI beyond time window has a definite effect, which can improve the blood lipid level, coagulation function and neurological function of patients, and help to improve the quality of life of patients, with good safety.

Rheumatoid arthritis is an autoimmune disease characterized by progressive bone destruction, with joint swelling caused by synovial inflammation in the early stage, and joint deformity caused by cartilage and bone destruction occurring in the middle and late stages as inflammation develops, resulting in a 75% disability and deformity rate within three years, and the prevention and treatment of RA bone and joint destruction is of urgency, and it is therefore of great significance to search for effective drugs to treat RA bone destruction. Studies have shown that wrinkled skin papaya can treat RA bone destruction, but the composition and mechanism of action are unknown, so this review aims to provide an overview of the mechanism of action of the effective active ingredients in wrinkled skin papaya for the treatment of rheumatoid arthritis bone destruction, and to provide a basis and direction for the development of novel formulations of traditional Chinese medicines for anti-RA bone destruction.

Type 2 diabetes mellitus (T2DM) is an insulin resistance disease. Improving insulin resistance and controlling blood glucose are the main means of clinical treatment for T2DM. Empagliflozin is a highly selective sodium-dependent glucose transporters (SGLT)2 inhibitor, which is independent of insulin. It can effectively control blood glucose levels, reduce blood pressure and body weight, protect heart and kidney function, reduce the rehospitalization rate and the risk of death in patients with heart failure (HF), and does not increase the risk of hypoglycemia. Empagliflozin can be used alone or in combination with other hypoglycemic drugs to control blood glucose. This article reviews the mechanism of action, clinical benefits, and combination with other drugs of empagliflozin, aiming to provide reference for the clinical use of empagliflozin.

Depression is a common mental disease. At present, there are poor efficacy and drug-related safety problems in antidepressant treatment. Toludesvenlafaxine, as a new triple reuptake inhibitor (TRIs/SNDRIs), increases the inhibitory effect of dopamine (DA) reuptake on the basis of serotonin (5-HT) and norepinephrine (NE), achieves multi-target synergistic therapy and reduces 5-HT/NE-related adverse drug reactions. This article reviews the basic introduction, preclinical research, clinical efficacy and safety of toludesvenlafaxine, in order to provide more ideas and options for the treatment of depression.

Artificial intelligence (AI) has emerged as a cutting-edge technology leading the future and is a key engine for China's development. In the innovation and research of medical devices, AI has provided critical support in the areas of intelligent diagnostic assistance, intelligent therapeutic assistance, intelligent monitoring, life support, et al. Machine learning-enabled device software functions (ML-DSFs) have become an essential component of many medical devices. Recently, the United States Food and Drug Administration (FDA) released a draft guidance titled " Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence/Machine Learning (AI/ML)-Enabled Device Software Functions (Draft). " that aimed to provide a forward-looking approach to foster the development of ML medical devices. By supporting iterative updates through modifications, this approach ensures the continuous safety and effectiveness of the devices. This guidance represents the latest in regulatory direction and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI products. Therefore, we plan to provide a detailed introduction and interpretation of the guidance, with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.