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:Exosomes,as a type of extracellular vesicle,have become a key medium for cell-to-cell communication due to their nanoscale size and enrichment of various bioactive substances.The study of exosome secretion regulation not only has important scientific value,but also has broad application prospects in clinical practice,and is of great significance for promoting medical progress and improving human health.OBJECTIVE:To review the biological characteristics,biological functions,biogenesis process and biochemical regulation mechanism of exosomes,and to explore the application prospects of exosomes in disease diagnosis,treatment and vaccine development,so as to provide theoretical basis and reference for basic research and clinical transformation of exosomes.METHODS:The first author searched PubMed and CNKI databases in October 2024 for relevant literature published from January 2010 to October 2024.Key words were"exosomes,biological functions,biogenesis,secretion or release,regulatory mechanisms,application prospects"in Chinese and English.Finally,92 articles were included for analysis.RESULTS AND CONCLUSION:The secretion level of exosomes can be regulated through physical or biochemical means.Exosomes show broad application prospects in the fields of disease diagnosis,treatment,and vaccine development,and may play a key role in the treatment of cardiovascular and cerebrovascular diseases as well as cancer.This review provides valuable information for the clinical translation and application research of exosomes,helping to promote future progress in exosome research and application.

BACKGROUND:Exosomes,as a type of extracellular vesicle,have become a key medium for cell-to-cell communication due to their nanoscale size and enrichment of various bioactive substances.The study of exosome secretion regulation not only has important scientific value,but also has broad application prospects in clinical practice,and is of great significance for promoting medical progress and improving human health.OBJECTIVE:To review the biological characteristics,biological functions,biogenesis process and biochemical regulation mechanism of exosomes,and to explore the application prospects of exosomes in disease diagnosis,treatment and vaccine development,so as to provide theoretical basis and reference for basic research and clinical transformation of exosomes.METHODS:The first author searched PubMed and CNKI databases in October 2024 for relevant literature published from January 2010 to October 2024.Key words were"exosomes,biological functions,biogenesis,secretion or release,regulatory mechanisms,application prospects"in Chinese and English.Finally,92 articles were included for analysis.RESULTS AND CONCLUSION:The secretion level of exosomes can be regulated through physical or biochemical means.Exosomes show broad application prospects in the fields of disease diagnosis,treatment,and vaccine development,and may play a key role in the treatment of cardiovascular and cerebrovascular diseases as well as cancer.This review provides valuable information for the clinical translation and application research of exosomes,helping to promote future progress in exosome research and application.

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.

OBJECTIVE To investigate the improvement effect and mechanism of modified Jinfeicao powder （MJCP） on cough-variant asthma （CVA） in rats.METHODS Network pharmacology was employed to identify the key targets and signaling pathways involved in the therapeutic action of MJCP against CVA. Rats were divided into normal control group， model group， positive control group （prednisone acetate， 0.9 mg/kg）， and MJCP low-， medium-， and high-dose groups （3.5， 7， 14 g/kg）， with six rats in each group. Except for the normal control group， CVA models were established in other groups. From day 14 of the experiment， rats in each group were administered corresponding drugs or normal saline intragastrically once daily for 14 consecutive days. After the final administration， cough frequency， serum levels of immune-inflammatory and oxidative stress-related indicators， pulmonary histopathological changes， and expression of pathway-related proteins were detected and observed.RESULTS Network pharmacology identified five key targets， including tumor necrosis factor-α （TNF-α）， interleukin-6（IL-6）， and protein kinase B（AKT）， as well as signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/AKT/mammalian target of rapamycin （mTOR） and hypoxia-inducible factor-1α （HIF-1α）. Animal experimental results showed that， compared with the model group， cough frequency was significantly reduced in all treatment groups （ P ＜0.05）. Serum levels of immunoglobulin E （IgE）， IL-6， TNF-α， Src family of protein tyrosine kinase， epidermal growth factor receptor， and malondialdehyde （MDA） （except for IgE and MDA in the MJCP low-dose group）， mean pathological scores， the ratio of total airway wall area to basement membrane perimeter， and the expression levels of α -smooth muscle actin， Collagen-Ⅰ， phosphorylated PI3K， phosphorylated AKT （except in the MJCP low-dose group）， phosphorylated mTOR， and HIF-1α protein in lung tissues were all significantly decreased （ P ＜0.05）. Glutathione （except in the MJCP low-dose group） and superoxide dismutase levels in serum were significantly increased（ P ＜0.05）.CONCLUSIONS MJCP may alleviate airway inflammation， airway remodeling， and oxidative stress by regulating the PI3K/AKT/mTOR and HIF-1α signaling pathways， thereby exerting its improvement effects on CVA.

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.

AIM: To analyze the clinical utility and value of the ultra-wide-field swept-source optical coherence tomography angiography(UWF-SS-OCTA)technique in changes of blood flow density and thickness in the central and peripheral regions of the retina and choroid in patients with nonproliferative diabetic retinopathy(NPDR)with or without diabetic kidney disease(DKD).METHODS: Cross-sectional study. Totally 50 cases(50 eyes)of diabetes mellitus(DM)that visited our hospital between June 2023 and June 2024 were included. They were divided into three groups: NPDR combined with DKD group(DKD group, n=20), NPDR without DKD group(NDKD group, n=20), and DM without retinopathy group(DM group, n=10, which served as control). In order to investigate the impact of DKD on ocular microangiopathy in NPDR patients, the retina and choroid within 24 mm×20 mm of the scan were separated into central and peripheral areas using the 3×3 nine-grid partition option that comes with UWF-SS-OCTA, and the parameters were then quantitatively assessed.RESULTS:The central and peripheral blood flow density of the choroidal capillary layer(CCP)was statistically significant between the DM group and the DKD group(t=3.93, P=0.0003; t=3.34, P=0.0016), and between the NDKD group and the DKD group(t=-3.06, P=0.003; t=-2.55, P=0.013), but there was no statistically significant difference between the DM group and the NDKD group(t=1.44, P=0.157; t=1.26, P=0.21). The mid-large choroidal vessel(MLCV)showed a progressive decline in central and peripheral blood flow density in the DM, NDKD, and DKD groups(F=13.74, 19.03, all P<0.0001). The DM, NDKD, and DKD groups saw a progressive decrease in central and peripheral choroidal thickness(CT; F=10.72, P=0.0001; F=13.12, P<0.001).CONCLUSION:CCP, MLCV, and CT can be used as visual indicators to identify impaired renal function in patients with NPDR. UWF-SS-OCTA can support the development of precise and noninvasive monitoring and treatment technology for diabetic ocular microangiopathy, while also offering a scientific foundation for the joint management of DR and DKD.

ObjectiveTo observe the clinical efficacy and safety of Guben Quyu Jiedu prescription in treating nocturnal hypoxemia of chronic obstructive pulmonary disease （COPD） combined with Obstructive sleep apnea hypopnea syndrome （ OSAHS ） （deficiency of lung， spleen and kidney with blood stasis and toxicity）. MethodsThe paper used a forward-looking， random double-blind， placebo-controlled design method to select 96 patients with COPD combined with OSAHS， and their traditional Chinese medicines （TCM） syndrome differentiation was deficiency of lung， spleen and kidney with blood stasis and toxicity. These patients were randomly divided into the observation group and the control group， with 48 cases in each group. Based on conventional Western medicine treatment， the observation group was treated with Guben Quyu Jiedu prescription and the control group was treated with traditional Chinese medicine placebo. Both courses of treatment were 90 days. Then the paper compared the changes in minimum pulse oxygen saturation （SpO₂） during the night， apnea index （AHI）， OSAHS efficacy evaluation， TCM syndrome efficacy evaluation， and TCM symptom score before and after treatment between the two groups. ResultsThere were 5 withdrawals in the observation group and 8 withdrawals in the control group， so 43 cases in the observation group and 40 cases in the control group completed the trial. Compared with the condition before treatment， the minimum SpO₂ during the night and AHI in the observation group were significantly improved at night （P<0.01） and were better than those in the control group （P<0.01）. OSAHS efficacy in the observation group was better than in the control group （χ²=7.085， P<0.05）. In terms of TCM syndrome efficacy， the total effective rate was 81.40% （35/43） in the observation group， significantly higher than that in the control group， which was 15.00% （6/40） （χ²=36.78， P<0.01）. The TCM symptom scores of the two groups were improved compared with the condition before treatment， and the effect of the two groups was similar in the four main symptoms of snoring， choking， lethargy， and cough. However， the observation group was better than the control group in 10 details such as dizziness， headache， chest tightness， chest pain， wheezing， dry mouth， and thirst （P<0.05）. ConclusionUsing Guben Quyu Jiedu prescription combined with conventional Western medicine can treat COPD combined with OSAHS hypoxemia at night （deficiency of lung， spleen and kidney with blood stasis and toxicity）. In this way， the minimum pulse oxygen saturation （SpO₂） of patients， the level of disease control， and the quality of life of patients can be improved， and the clinical symptoms can be relieved.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.