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.

Objective: To analyze the epidemiological characteristics and disease types of extrapulmonary tuberculosis in Ningbo City, Zhejiang Province from 2015 to 2024, so as to provide evidence for optimizing regional tuberculosis prevention and control strategies. Methods: Data on extrapulmonary tuberculosis cases in Ningbo City from 2015 to 2024 were collected through the Ningbo Infectious Disease Surveillance and Early Warning Platform, including gender, age, and disease type. Descriptive analysis was conducted to examine the temporal, regional, and population distributions as well as the distribution of disease types of extrapulmonary tuberculosis in Ningbo City from 2015 to 2024. The trend chi-square test was used to analyze the temporal trends in the incidence and proportion of extrapulmonary tuberculosis. Results: From 2015 to 2024, a total of 11 023 cases of extrapulmonary tuberculosis were reported in Ningbo City, accounting for 25.17% of tuberculosis cases. The proportion showed an increasing trend (P<0.05), with an annual increase rate of 2.15%. The average annual incidence of extrapulmonary tuberculosis was 12.77/105, showing a decreasing trend (P<0.05), with an annual decline rate of 3.18%. In the second quarter, a higher number of extrapulmonary tuberculosis cases were reported, with 3 108 cases, accounting for 28.20%. Beilun District, Yuyao City, and Fenghua District had relatively high average annual incidence of extrapulmonary tuberculosis, at 16.43/105, 15.28/105, and 14.97/105, respectively. The average annual incidence of extrapulmonary tuberculosis in males was lower than in females (10.73/105 vs. 14.93/105, P<0.05). The annual average incidence of extrapulmonary tuberculosis was relatively high among cases aged 65-<75 years, 75-<85 years, and ≥85 years, respectively. The 15-<25 years age group exhibited a higher number of cases of tuberculous peripheral lymphadenopathy, with 253 cases, accounting for 34.90%. The proportion of osteoarticular tuberculosis cases among extrapulmonary tuberculosis cases increased with advancing age (P<0.05). Conclusions From 2015 to 2024, the incidence of extrapulmonary tuberculosis in Ningbo City showed a decreasing trend, while its proportion among all tuberculosis cases showed an increasing trend. Beilun District, Yuyao City, and Fenghua District were high-incidence areas, and females and the elderly were high-risk population. Tuberculous peripheral lymphadenopathy was highly prevalent among young adults, while osteoarticular tuberculosis was highly prevalent among the elderly.

In this paper， the name， origin， producing area， harvesting， processing and functional indications of Arcae Concha were systematically combed and verified by consulting the ancient and modern literature， in order to provide a basis for the development of famous classical formulas containing Arcae Concha. Arcae Concha was first recorded in the name of Han in Bencao Shiyi， but later， due to the influence of LI Shizhen's error of combining Han item with Kuiha in the Ming dynasty， there were aliases such as Kuilu and Fulao， and Yizong Bidu began to include Walengzi as its correct name and has been used ever since. The textual descriptions and illustrations of the medicinal materials of Arcae Concha contained in the materia medica of the past generations were consistent with the modern Arca inflata， A. subcrenata and A. granosa. In ancient times， there were medicinal records of two parts of shell and meat， but now the shell is used as medicine， and the meat is mostly edible. In ancient times， Zhejiang， Shandong， Guangdong and Guangxi were the main producing areas， and Zhejiang was the best. It is now believed that A. inflata is mostly distributed in the northern part of the Huanghai Sea， A. granosa is mostly distributed in the coastal areas south of Shandong Peninsula in China， and A. subcrenata is widely distributed in the coastal areas of China. Its quality is better in a complete， white， no residual meat and sand. In ancient times， there was no clear harvesting period， and the processing was mainly based on vinegar quenching after calcination or powdering of calcined shell， but now the harvesting period is autumn and winter. After harvesting， it is directly washed and crushed for raw use or processed by calcined method. The records of the medicinal materials in the past dynasties on the properties of Arcae Concha were mainly warm， sweet， salty and mild， and it is now believed that Arcae Concha is salty in taste and mild in nature. In ancient times， it was believed that Arcae Concha were mainly used for coldness in the heart and abdomen， coldness in the waist and spine， benefiting the five internal organs， strengthening the stomach. Nowadays， it is believed that Arcae Concha can eliminate phlegm and remove blood stasis， soften the hardness and dissipate the lumps， produce acid and relieve pain. It can be used in the treatment of stubborn phlegm， gall tumor， scrofula and other symptoms. In conclusion， it is suggested that for the famous classical formulas containing Arcae Concha， the corresponding methods should be selected according to the processing requirements of the drug in the formulas， while those without processing requirements can be determined according to the functional position of the products.

ObjectiveTo investigate the mechanism of action of modified Shaofu Zhuyutang in antagonizing cellular pyroptosis and fibrosis in ectopic endometrial tissues of endometriosis through the Toll-like receptor 4/nuclear factor-κB/NOD-like receptor protein 3 （TRL4/NF-κB/NLPR3） signaling pathway. MethodsSeventy-two SPF-grade female SD rats were randomly divided into a sham-operated group （n = 12） and a modeling group （n = 60）. The rats in the sham-operated group underwent a caesarean section， while the rats in the modeling group were used to establish an endometriosis model through the auto-transplantation method. After successful modeling， the animals were randomly divided into the model group， progesterone group （0.25 mg·kg^-1）， and modified Shaofu Zhuyutang low-， medium-， and high-dose groups （7.5， 15， 30 g·kg^-1）， with 12 animals in each group. After 4 weeks of drug administration， voluntary activity and heat pain latency were observed. The rats were sacrificed for tissue collection， and Masson staining were used to observe histopathological changes in the endometrial tissues. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of interleukin-18 （IL-18）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β （TGF-β）. Immunohistochemistry （IHC） was used to detect the protein expression area of tumor necrosis factor-related factor 6 （TRAF6） and NLPR3 in the endometrial tissues. Immunofluorescence （IF） was used to detect the relative fluorescence intensity of Caspase-1 and gasdermin D （GSDMD） in the endometrial tissues. Western blot was employed to measure the relative expression of TRL4， myeloid differentiation factor 88 （MyD88）， TRAF6， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， and NLPR3 proteins in endometrial tissues. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of TRL4， MyD88， TRAF6， NF-κB， and NLPR3 in the endometrial tissues. ResultsCompared with the sham-operated group， rats in the model group showed reduced voluntary activity and shorter heat pain latency. Serum levels of IL-18， IL-1β， TNF-α， and TGF-β were elevated. The relative expression areas of TRAF6 and NLPR3 proteins were increased， and the relative fluorescence intensity of Caspase-1 and GSDMD was enhanced. The relative expression of TRL4， MyD88， TRAF6， NF-κB p65， p-NF-κB p65， and NLPR3 proteins， along with the expression of TRL4， MyD88， TRAF6， NF-κB， and NLPR3 mRNA， were significantly increased （P<0.01）. Compared with the model group， rats in the progesterone group and the modified Shaofu Zhuyutang medium- and high-dose groups exhibited improved voluntary activity， longer heat pain latency， the fibrosis of endometrial tissue is alleviated. Serum levels of IL-18， IL-1β， TNF-α， and TGF-β were decreased. The relative expression areas of TRAF6 and NLPR3 proteins decreased， and the relative fluorescence intensity of Caspase-1 and GSDMD weakened. The relative expression of TRL4， MyD88， TRAF6， p-NF-κB p65， NLPR3 proteins， and TRL4， MyD88， TRAF6， NF-κB， and NLPR3 mRNA expression were reduced （P<0.05， P<0.01）. ConclusionModified Shaofu Zhuyutang may play a therapeutic role in endometriosis by interfering with key proteins in the TRL4/NF-κB/NLPR3 signaling pathway， reducing NLRP3 inflammasome-induced cellular pyroptosis， antagonizing the fibrosis process in ectopic endometrial tissues， improving the inflammatory microenvironment in the pelvic cavity， and alleviating pain.

Objective To investigate the effects of different use methods of tourniquet on hidden blood loss and knee joint swelling in total knee arthroplasty(TKA),and to explore its potential benefits for postoperative rehabilitation.Methods A prospective study was conducted from March 2018 to March 2023 in Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University,involving 131 patients who underwent TKA.The patients were divided into three groups based on the method of tourniquet use:44 patients routinely used a tourniquet in group A,48 patients only used a tourniquet during the application of bone cement in group B,and 39 patients did not use tourniquet in group C.Operation time,dressing changes,intraoperative blood loss,total blood loss,explicit blood loss,hidden blood loss,percentage of hidden blood loss,postoperative blood transfusion,hemoglobin(Hb),hematocrit(HCT),C-reactive protein(CRP),and creatine kinase(CK)were compared among groups.The pain and functional recovery were evaluated by visual analogue scale(VAS)and knee society clinical rating system(KSS)before surgery,and 3 days,1 month,and 3 months after surgery.The degree of limb swelling and the range of motion of the knee were also compared among groups.Results Group A had shorter operation time and less frequency of postoperative dressing changes than the other two groups(P<0.05).The hidden blood loss and total blood loss in group A were significantly less than those in group C(P<0.05),and the hidden blood loss and total blood loss volume in the three groups from low to high was group A

Diabetic cardiomyopathy （DCM）， a cardiovascular complication caused by diabetes mellitus， is a major cause of heart failure and even sudden cardiac death in diabetic patients. Traditional Chinese medicine （TCM） posits that the core pathogenesis of DCM lies in internal deficiency and superficial excess， characterized by deficiency of both Qi and Yin combined with phlegm and blood stasis. Modern medical treatments for DCM primarily focus on blood glucose control and symptom alleviation yet lack targeted therapeutic strategies. In contrast， TCM offers a wealth of practical experience and a complete theoretical system， demonstrating definite clinical efficacy and high medication safety in DCM management. As a classic formula for tonifying Qi and nourishing Yin， Shengmaisan comprises Ginseng Radix et Rhizoma， Ophiopogonis Radix， and Schisandrae Chinensis Fructus. It contains multiple bioactive components， including ginsenosides， ophiopogonin， schisandrins， and homoisoflavonoids， which exhibit cardioprotective properties. The therapeutic mechanisms of Shengmaisan-like formulae for DCM involve enhancing myocardial contractility， attenuating myocardial fibrosis， modulating mitochondrial quality control， regulating glucose metabolism， mitigating oxidative stress， and suppressing inflammatory responses. Clinically， Shengmaisan-like formulae not only manage hyperglycemic status but also ameliorate cardiac structural and functional impairments and enhance exercise tolerance in DCM patients， playing a vital role in the prevention， treatment， and rehabilitation of DCM. This paper analyzes the feasibility of Shengmaisan-like formulae in DCM management and synthesizes current research achievements regarding their chemical components， mechanisms of action， and clinical applications， aiming to provide a scientific foundation for the use of such formulae in the treatment of DCM.

Guided by Academician Zhang Boli's theory of "dampness， turbidity， phlegm， and fluid-related diseases"，this paper elaborated on the pathogenesis and syndrome differentiation treatment of heart failure from the perspective of the "spleen-mitochondria". It analyzed the essential similarities between "spleen-mitochondria" and "dampness， turbidity， phlegm， and fluid-related diseases"， as well as their close association with the onset of heart failure. Furthermore，it explored the connection between spleen function and mitochondrial function in traditional Chinese medicine （TCM），positing that the spleen's role in transportation and transformation is analogous to mitochondrial material metabolism and energy conversion，with spleen deficiency closely related to mitochondrial dysfunction. It thus concluded that mitochondrial material metabolism and energy conversion represent the microscopic essence of the spleen's role in transportation and transformation，and mitochondrial dysfunction is a contributing factor to pathological products like dampness and turbid phlegm，which are closely associated with the occurrence of heart failure. The four elements of dampness，turbidity，phlegm，and fluid are a series of related symptoms resulting from abnormal fluid transportation and transformation，serving as both factors in the onset of heart failure and the core pathological basis for its deterioration. Therefore，during the treatment of heart failure，it is essential to regulate mitochondrial function. Early intervention should focus on eliminating dampness and turbidity to improve mitochondrial function and restore normal energy metabolism. In the middle and late stages，emphasis should be placed on resolving phlegm，promoting blood circulation，warming Yang，and reducing water retention to alleviate mitochondrial damage and improve cardiac function. Supporting Qi and strengthening the spleen should be a continuous approach，and treatment should be adjusted to enhance mitochondrial function and stabilize the condition，thereby improving prognosis. This paper discussed the role of the spleen and mitochondria in the pathogenesis of heart failure，examined the evolution of heart failure mechanisms from the perspective of dampness， turbidity， phlegm， and fluid-related diseases，and proposed a phased treatment strategy. It enriched the theory of dampness， turbidity， phlegm， and fluid-related diseases and offered new strategies for heart failure treatment. However，in practical application，TCM strategies for treating heart failure need to be integrated with modern medical approaches to provide a more solid scientific foundation for treatment.

Objective:To explore the correlation between serum nidogen-2 (NID-2) and thoracic aortic calcification in patients with chronic kidney disease (CKD), and construct a risk prediction model based on NID-2 to evaluate its value in predicting the risk of the severe thoracic aortic calcification and cardiovascular and cerebrovascular events in CKD patients.Methods:It was a prospective cohort study. Patients with CKD at stage 3 to 5D in the Zhongda Hospital Affiliated to Southeast University from January 2022 to January 2023 were enrolled. Syngo.via software was used to evaluate the volume of thoracic aortic calcification, and enzyme-linked immunosorbent assay was employed to determine the level of serum NID-2. According to the volume of thoracic aortic calcification, the patients were divided into three groups: no calcification group, mild calcification group and severe calcification group. The top 25% of the patients were defined as no or mild calcification group, and the latter 75% were defined as severe calcification group. The follow-up period was one year. During the follow-up period, cardiovascular and cerebrovascular events, as well as all-cause death among the enrolled patients were recorded. Logistic regression analysis was used to screen the influencing factors of thoracic aortic calcification. Based on the results of logistic regression analysis, a nomogram prediction model was constructed. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve were employed to evaluate the discrimination, calibration and clinical practicality of the nomogram model.Results:A total of 132 patients were included, with 91 males (68.94%) and age of (56.51±16.37) years. There were 60 CKD 3-5 stage patients (non-dialysis, 45.45%) and 72 CKD 5D patients (dialysis, 54.55%). Serum ND-2 levels differed significantly among healthy individuals, dialysis patients and non-dialysis patients ( H=70.651, P<0.001). There was no statistically significant difference in serum NID-2 level between the no or mild calcification group and the severe calcification group in dialysis patients ( Z=350.00, P=0.426). The serum NID-2 level in the severe calcification group was significantly higher than that in the no or mild calcification group in non-dialysis patients ( Z=242.00, P=0.019). In non-dialysis patients, there was a statistically significant correlation between serum NID-2 level and volume of thoracic aortic calcification ( r=0.40, P<0.001). In dialysis patients, there was no statistically significant correlation between serum NID-2 level and volume of each segment of thoracic aortic calcification (all P>0.05). The univariate logistic regression analysis showed that, age, hemoglobin, serum albumin, estimated glomerular filtration rate, NID-2, hypertension, type 2 diabetes mellitus and cerebral infarction were correlated factors of thoracic aortic calcification in non-dialysis patients (all P<0.05). Multivariate logistic regression analysis showed that age ( OR=1.22, 95% CI 1.08-1.50, P=0.010) was an independent correlated factor of thoracic aortic calcification in non-dialysis patients. The above related variables of univariate logistic regression analysis were incorporated into a nomogram to construct a predictive model for severe vascular calcification in non-dialysis patients, yielding an AUC of 0.94 (95% CI 0.89-0.99) in ROC curve, with a sensitivity of 83% and a specificity of 95%. A nomogram model based on above variables for predicting cardiovascular and cerebrovascular events in non-dialysis patients demonstrated an AUC of 0.95 (95% CI 0.90-1.00) in ROC curve, with a sensitivity of 95% and a specificity of 87%. Conclusions:In non-dialysis patients, serum NID-2 level in the severe calcification group is significantly higher than that in the no or mild calcification group. The serum NID-2 is a related factor of thoracic aortic calcification and cardiovascular and cerebrovascular events in non-dialysis patients. The nomogram prediction model constructed by combining NID-2 with age, hemoglobin, serum albumin, estimated glomerular filtration rate, hypertension, type 2 diabetes mellitus and cerebral infarction has a high predictive value for the risk of thoracic aortic calcification as well as cardiovascular and cerebrovascular events in non-dialysis patients.