As an innovative form of combining traditional aromatherapy with modern nasal medicine delivery technology， "olfactory administration of Chinese medicine" carries the theoretical essence of traditional Chinese medicine （TCM）， which is "moving and channeling Qi and fragrance， dredging and awakening the mind". Based on the systematic records of olfactory therapies in ancient books in emergency care， disorders of consciousness， lung system， and gynecological diseases， this paper examines the historical evolution of its clinical application， and elucidates the profound historical basis and theoretical feasibility of "olfactory administration of Chinese medicine" as a new form. Combined with the innovation and precise application of modern Chinese medicine olfactory agents in multi-system diseases such as nervous， respiratory， and cardiovascular diseases， this paper further analyzes the multi-dimensional mechanism of olfactory receptor pathway， olfactory brain pathway， nasal mucosal blood vessels， and lymphatic channels， and demonstrates its advantages of rapid onset， targeted brain entry， and systemic regulation. Under the background of continuous growth in the demand for external TCM treatment， continuous breakthroughs in the technology of nasal dosage forms， and increasingly accurate drug delivery paths， Chinese medicine olfactory agents have shown significant practical applicability and development potential. This study aims to provide theoretical support and practical direction for the system construction of this form.

The nose-to-brain pathway refers to a significant drug delivery route through which substances traverse the unique anatomical structures of the nasal cavity to directly access the central nervous system， bypassing the blood-brain barrier. Its core advantage lies in utilizing the olfactory and trigeminal nerves， enabling peripheral drug administration to rapidly and efficiently reach the brain， thereby avoiding the drug loss and bioavailability reduction associated with oral or intravenous routes due to the circulatory system and blood-brain barrier limitations. In recent years， with in-depth research into the neuroanatomy of the olfactory system， nasal mucosal barrier properties， and neural regulatory mechanisms， the potential application of the nose-to-brain pathway in neurological diseases has attracted increasing attention. Traditional Chinese medicine （TCM） essential oils， characterized by strong lipophilicity， small molecular weights， volatility， and diverse chemical components， are highly compatible with the physiological characteristics of the nose-to-brain pathway， thus serving as promising carriers for brain-targeted drug delivery， enhancing drug bioavailability， and exerting neuroprotective effects. On this basis， this review systematically summarizes the anatomical and physiological bases for the delivery of TCM essential oils via the nose-to-brain pathway， the patterns of drug transport and brain distribution， clinical and animal study examples in neurological diseases， the associated molecular mechanisms and signaling pathways， and the progress in the development of novel nasal essential oil formulations. Additionally， the review analyzes the current challenges in this field and proposes strategies for future research and application. By systematically discussing the nose-to-brain pathway and the delivery mechanisms of TCM essential oils， this study aims to provide theoretical support for drug development， mechanism exploration， and formulation innovation in the treatment of neurological diseases， while also offering scientific guidance for further research and clinical applications of the nose-to-brain delivery system.

The nose-to-brain pathway refers to a significant drug delivery route through which substances traverse the unique anatomical structures of the nasal cavity to directly access the central nervous system， bypassing the blood-brain barrier. Its core advantage lies in utilizing the olfactory and trigeminal nerves， enabling peripheral drug administration to rapidly and efficiently reach the brain， thereby avoiding the drug loss and bioavailability reduction associated with oral or intravenous routes due to the circulatory system and blood-brain barrier limitations. In recent years， with in-depth research into the neuroanatomy of the olfactory system， nasal mucosal barrier properties， and neural regulatory mechanisms， the potential application of the nose-to-brain pathway in neurological diseases has attracted increasing attention. Traditional Chinese medicine （TCM） essential oils， characterized by strong lipophilicity， small molecular weights， volatility， and diverse chemical components， are highly compatible with the physiological characteristics of the nose-to-brain pathway， thus serving as promising carriers for brain-targeted drug delivery， enhancing drug bioavailability， and exerting neuroprotective effects. On this basis， this review systematically summarizes the anatomical and physiological bases for the delivery of TCM essential oils via the nose-to-brain pathway， the patterns of drug transport and brain distribution， clinical and animal study examples in neurological diseases， the associated molecular mechanisms and signaling pathways， and the progress in the development of novel nasal essential oil formulations. Additionally， the review analyzes the current challenges in this field and proposes strategies for future research and application. By systematically discussing the nose-to-brain pathway and the delivery mechanisms of TCM essential oils， this study aims to provide theoretical support for drug development， mechanism exploration， and formulation innovation in the treatment of neurological diseases， while also offering scientific guidance for further research and clinical applications of the nose-to-brain delivery system.

BACKGROUND: The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting. METHODS: The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves. RESULTS: A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year. CONCLUSION: The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03916432.
Humans ; Middle Aged ; Sirolimus/therapeutic use* ; Drug-Eluting Stents/adverse effects* ; Prospective Studies ; Cohort Studies ; Treatment Outcome ; Risk Factors ; Time Factors ; Percutaneous Coronary Intervention/adverse effects* ; Cardiovascular Agents/therapeutic use* ; Coronary Artery Disease/therapy* ; Myocardial Infarction/etiology* ; Thrombosis/complications* ; Polymers ; Registries

Lung cancer is the most common malignant tumor in the world. In order to improve the survival rate of patients with advanced lung cancer, more effective treatment methods are needed,in which immunotherapy has a broad therapeutic prospect. In recent years, immune-checkpoint inhibitors have received extensive attention in the treatment of lung cancer. Significant progress has been made in the development of a variety of first-line and second-line treatments, and significant advances have been made in the treatment of advanced lung cancer. With the successful application of immune-checkpoint inhibitors, neoadjuvant therapy has attracted extensive attention. In addition, the successful application of combined therapies such as immune combined immunization, immune combined tyrosine kinase inhibitor (TKI) and immune combined chemotherapy improved the survival rate of patients to some extent. However, pseudo progression and drug resistance has become a non-negligible problem in the immunotherapy of non-small cell lung cancer, which is worthy of further study. Although immune-checkpoint inhibitors have once again brought attention to tumor immunotherapy, their side effects are also worthy of attention. The recent advances in the application of immune-checkpoint inhibitors in lung cancer were summarized in order to provide a theoretical basis for its clinical application.

Objective To evaluate the incidence of net adverse clinical and cerebral events (NACCE) 1 year after implantation of biodegradable polymer stents (BP-SES) in elderly patients with coronary artery disease.Methods The clinical data of patients inserted with BP-SES in I-LOVE-IT 2 Trial were retrospectively analyzed, including 1829 elderly patients admitted in the General Hospital of Shenyang Military Command from Oct. 2012 to Jun. 2013, of which 62 cases aged equal to and more than 65 years (elderly group) and 1202 cases less than 65 years (non-elderly group). The primary end-point of this research was target lesion failure (TLF) rate on 12 months and the secondary end-point was the incidence of NACCE, including all-cause death, all myocardial infarction, stroke and severe hemorrhage (BARC type ≥3), and then the multiple regression analysis was performed.Results The Baseline conditions of the two groups were significantly different (P<0.05) including BMI, diabetes, hypertension, hyperlipidemia, family history of coronary heart disease, smoking history, past stroke history, history of peripheral vascular disease and stable angina pectoris. When comparing elderly group with non-elderly group, marked differences existed on the incidence of NACCE (10.0%vs. 5.2%,P<0.01), all-cause mortality (2.7%vs. 0.7%,P<0.01), myocardial infarction (5.6%vs. 3.5%,P=0.03), stent thrombosis (1.9%vs. 0.5%,P<0.01) and stroke (2.2%vs. 0.8%,P=0.01). Multiple regression analysis revealed that elderly (age ≥65) was the independent predictive factor for NACCE (OR=1.904, 95%CI 1.304-2.781,P=0.001).ConclusionThe incidence of NACCE is increased significantly in elderly patients (age ≥65), and elderly is an independent predictive factors for 12-month NACCE in patients implanted with BP-SES

Objective To establish the method of combined hepatocyte growth factor (HGF) with epidermal growth factor (EGF) cultured human gallbladder epithelial cells(HGBECs) in vitro .Methods The epithelial layer was peeled away from human gallbladder ,epithelial layer were digested with collagenase Ⅳ and scraped repeatedly .HGBECs were isolated and seeded in cell cul-ture plates containing medium supplemented with or without 10 ng/mL EGF or with 10 ng/mL HGF and 10 ng/mL EGF respec-tively .Then the morphologic changes of the cells were observed and taken photos with inverted phase contrast microscope ,and counted number of cells ,MTT assay detected vigor of cells in different groups .Results The number of the HGBECs of the HGF+EGF group was obviously more than the EGF group ,the duration of the HGBECs of the HGF+ EGF group was obviously longer than the EGF group(19 .3 ± 2 .5)d vs .(14 .2 ± 2 .4)d ,P< 0 .05 .And the HGBECs of the group with HGF+ EGF had better cell vigor .Conclusion HGF combines with EGF added to medium can obviously promote the proliferation of HGBECs and prolong the duration and stabilize morphology of HGBECs in vitro .

Objective:To investigate the relationship between serum carcinoembryonic antigen (CEA) and the predictive value of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer patients, as well as to analyze further EGFR muta-tions and CEA levels affecting patient survival. Methods:From March 2009 to March 2011, a total of 387 cases were treated in the Lung Cancer Department in Tianjin Cancer Hospital. Preoperative CEA tumor marker and postoperative EGFR gene mutation were used for routine detection. The influence of CEA tumor marker on EGFR mutation and its relationship with the prognosis were ana-lyzed further. Results:A total of 168 cases involved EGFR mutations, the incidence of which is more frequent in women, non-smokers, adenocarcinoma patients, and patients below 60 years old (P<0.05). This study also determined that EGFR mutation was related with tu-mor markers and chemosensitivity indicators. Elevated Cyfra21-1, SCC, and ERCC1-positive are more common in wild-type patients (P<0.05). However, abnormal CEA was more common in EGFR mutation patients (P=0.015). The rate of EGFR gene mutations signifi-cantly increased as the serum CEA level increased. Serum CEA levels were divided into three groups (<5, 5-20, and>20). The positive rates of EGFR mutations were 40.1%, 47.5%and 66.6%(P=0.003). Logistic regression analysis determined that CEA levels are inde-pendent factors in predicting EGFR mutations and independent prognostic factors in patients with non-small cell lung cancer. Conclu-sion:Serum CEA levels can independently predict the prognosis of resected non-small cell lung cancer patients, which is has a close re-lationship with EGFR mutations.

OBJECTIVEThe aim of this study was to investigate the effects of combination of icotinib and cetuximab on the acquired drug resistance caused by T790M mutation of EGFR in NSCLC, and provide experimental evidence for rational treatment of NSCLC.

METHODSThe effects of these two agents on cell proliferation, apoptosis, and EGFR-dependent signaling were evaluated using 3-(4, 5-dimethylthiazol-2-yl)- 5-diphenyltetrazolium bromide (MTT) assay, annexin V staining, and Western blotting. The expression of molecular markers of tumor proliferation PCNA and Ki-67 protein was further examined by immunohistochemistry, and the expression of EGFR-signaling-related proteins in tissue sections taken from H1975 tumor xenografts was assessed by Western blot assay. Sensitivity to EGFR inhibitors was detected in human H1975 tumor xenograft in nude mice.

RESULTSThe in vitro experiment showed that the proliferative ability of H1975 cells was inhibited in a dose-dependent manner, along with the increasing doses of cetuximab and icotinib, and the combination of cetuximab with icotinib resulted in a more pronounced growth inhibition of the H1975 cells. The apoptosis rate of H1975 cells after treatment with 0.5 µmol/L icotinib and 1 µg/ml cetuximab was (22.03 ± 2.41)% and that after treatment with 5 µmol/L icotinib and 10 µg/ml cetuximab was (42.75 ± 2.49)%, both were significantly higher than that after treatment with the same dose of icotinib or cetuximab alone (P < 0.05). The nude mouse experiment showed that the transplanted tumor was growing to (614.5 ± 10.8) mm(3) in the blank control group and to (611.2 ± 8.7) mm(3) at 28 days after icotinib treatment, but (30.8 ± 2.0) mm(3) in the cetuximab treatment group and 0 mm(3) in the cetuximab combined with icotinib group. There was a significantly decreased expression of Ki-67 and PCNA proteins and down-regulation of phosphorylation of EGFR signaling-related proteins in the cetuximab combined with icotinib group.

CONCLUSIONSThe combination of icotinib with cetuximab can exert synergistic inhibitory effect on the acquired drug resistance caused by T790M mutation of EGFR in NSCLC H1975 cells, interrupts the EGFR-downstream signaling pathway, and enhances the anticancer activity of chemotherapeutic drugs. Our results provide further experimental evidence for the clinical studies of combination of icotinib with cetuximab in the treatment of NSCLC patients associated with secondary drug resistance caused by T790M mutation of EGFR.

Animals ; Antibodies, Monoclonal, Humanized ; administration & dosage ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Apoptosis ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Cell Line, Tumor ; Cell Proliferation ; Cetuximab ; Crown Ethers ; administration & dosage ; therapeutic use ; Down-Regulation ; Drug Resistance, Neoplasm ; genetics ; Genes, erbB-1 ; genetics ; Humans ; Lung Neoplasms ; drug therapy ; Mice ; Mice, Nude ; Mutation ; Quinazolines ; administration & dosage ; therapeutic use ; Receptor, Epidermal Growth Factor ; Signal Transduction

OBJECTIVETo develop a new method to rapidly determine and identify Guizhi Fuling capsule by portable acousto-optic tunable filter-near infrared spectroscopy.

METHODThe qualitative model was set up using principal component analysis. The correlation models between the NIR spectra and the reference values of five major constituents were obtained with partial least squares method.

RESULTThe identifying model accurately identified Guizhi Fuling capsule, and quantitative analytical models could precisely predicted the content of ellagic acid, baicalin, benzoylpaenoniflorin, cinnamaldehyde, and paeonol. The correlation coefficients of the calibration models were 0.924 2, 0.938 4, 0.924 2, 0.933 6, 0.934 7, the validation set coefficients of the calibration were 0.924 2, 0.938 4, 0.924 2, 0.933 6, 0.934 7, and the RMSEP were 1.138%, 3.014%, 0.751%, 0.625%, 3.455%, 1.363%, respectively. The results of external validation showed no significant difference between the predictive and the determining values by t-test.

CONCLUSIONThe method is accurate, rapid and non-destructive, and can be used for determining and identifying Guizhi Fuling capsule.

Acetophenones ; analysis ; Acrolein ; analogs & derivatives ; analysis ; Calibration ; Capsules ; chemistry ; Drug Evaluation ; methods ; Drugs, Chinese Herbal ; analysis ; Ellagic Acid ; analysis ; Flavonoids ; analysis ; Least-Squares Analysis ; Models, Chemical ; Principal Component Analysis ; methods ; Spectroscopy, Near-Infrared ; methods