Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Objective:To understand the awareness and influencing factors of core information on tuberculosis prevention and control in the elderly population in China.Methods:The study included all participants aged ≥60 from the "13 th Five-Year" National Tuberculosis Control Plan end-term assessment in 2020, with 13 706 valid questionnaires obtained. Multivariate logistic regression was used to analyze the influencing factors of the awareness rate of core information on tuberculosis prevention and control in the elderly. Results:The total awareness rate of core information on tuberculosis prevention and control in the elderly aged ≥60 was 78.4%, with the highest for "suspicious symptoms of pulmonary tuberculosis" (85.4%) and the lowest for "whether pulmonary tuberculosis can be cured" (65.3%). The complete awareness rate of core information on tuberculosis prevention and control in the elderly was 41.3%, and the proportion of those who received tuberculosis health education is 67.6%. Multivariate logistic regression analysis results showed that factors associated with low awareness of core information included females ( OR=0.93, 95% CI: 0.86-1.00), ages 70- ( OR=0.91, 95% CI: 0.84-0.98) and ≥80 ( OR=0.77, 95% CI: 0.68-0.87) and minority ethnicity ( OR=0.85, 95% CI: 0.74-0.99). Factors associated with high awareness of core information included educational levels of junior high school ( OR=1.46, 95% CI: 1.34-1.58), high school ( OR=1.62, 95% CI: 1.45-1.81), junior college ( OR=1.37, 95% CI: 1.11-1.68), and an undergraduate degree or higher ( OR=1.52, 95% CI: 1.09-2.11), and receiving tuberculosis health education ( OR=2.13, 95% CI: 1.97-2.27). Conclusions:In 2020, the awareness rate of core information on tuberculosis prevention and control in Chinese older adults aged ≥60 was lower than the national planning target. Therefore, there should be an increased focus on health education about tuberculosis for elderly females, those aged ≥70, ethnic minorities, and those with lower education levels.

Vertebral artery hypoplasia(VAH)may lead changes of hemodynamic status in the posterior circulation,promote occurrence of intracranial atherosclerotic disease and formation of thrombi,hence result in hypoperfusion and infarction in posterior circulation cerebral tissue,which is potentially associated with posterior circulation cerebral vascular degeneration,vertebral artery dissection,cardiac disease and so on,also is a risk factor for posterior circulation infarction(PCI).The progresses of imaging researches revealing the association between VAH and PCI were reviewed in this article.

Cardiovascular diseases, including heart failure, coronary artery disease, atherosclerosis, aneurysm, thrombosis, and hypertension, are a great economic burden and threat to human health and are the major cause of death worldwide. Recently, researchers have begun to appreciate the role of microbial ecosystems within the human body in contributing to metabolic and cardiovascular disorders. Accumulating evidence has demonstrated that the gut microbiota is closely associated with the occurrence and development of cardiovascular diseases. The gut microbiota functions as an endocrine organ that secretes bioactive metabolites that participate in the maintenance of cardiovascular homeostasis, and their dysfunction can directly influence the progression of cardiovascular disease. This review summarizes the current literature demonstrating the role of the gut microbiota in the development of cardiovascular diseases. We also highlight the mechanism by which well-documented gut microbiota-derived metabolites, especially trimethylamine N-oxide, short-chain fatty acids, and phenylacetylglutamine, promote or inhibit the pathogenesis of cardiovascular diseases. We also discuss the therapeutic potential of altering the gut microbiota and microbiota-derived metabolites to improve or prevent cardiovascular diseases.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Abstract Astragalus polysaccharides(APS), as one of the main active components of Astragali Radix, a traditional famous tonic drug in China, has good pharmacological effects in regulating immunity and anti-oxidation. In recent years, with the success of PD-1/PD-L1 inhibitors and anti-CTLA-4 drugs in cancer treatment, immunotherapy has truly become one of the main clinical anti-tumor treatment methods. Aiming at the characteristics of tumor immune escape and tumor microenvironment change, this paper explores the clinical potential of APS as an anti-tumor adjuvant drug, and summarizes the role and mechanism of APS in inhibiting tumor immune escape, regulating tumor microenvironment, and improving immune function. To summarize and analyze the immune regulation of APS on various tumors in order to provide an objective basis for APS as a clinical anti-tumor adjuvant drug.

Objective:To evaluate the efficacy and safety of lumen-apposing metal stent (LAMS) for the treatment of pancreatic walled-off necrosis (WON).Methods:A retrospective cohort study was performed on data of 43 consecutive patients with pancreatic WON who underwent endoscopic ultrasound-guided drainage by LAMS or plastic stents (PS) in Hangzhou First People's Hospital from December 2010 to June 2020. According to the type of stent used, the patients were divided into the LAMS group ( n=16) and the PS group ( n=27). The technical success rate, the clinical success rate, the operation time, the session of endoscopic necrosectomy, the stent insertion time and adverse events were compared between the two groups. Results:All 43 patients were successfully stented, indicating a technical success rate of 100% in both groups. For the LAMS group, the clinical success rate, the operation time, the session of endoscopic necrosectomy, the stent insertion time and overall incidence of adverse events were 75.0% (12/16), 26.0 (19.1, 39.8) min, 0.5 (0, 2.0) times, (41.3±28.4) days, and 43.7% (7/16), respectively, whereas these indices of the PS group were 37.0% (10/27) ( χ2=5.795, P=0.016), 31.0 (26.0, 48.0) min ( Z=1.221, P=0.222), 0 (0, 0) times ( Z=2.245, P=0.025), (176.1±99.1) days ( t=5.187, P<0.001) and 14.8% (4/27) ( χ2=8.893, P=0.064), respectively. Conclusion:LAMS placement is safe and effective for the treatment of pancreatic WON with a higher clinical success rate compared with PS. However, it requires more endoscopic intervention.

Esophagectomy and lymph node dissection are the cornerstones for the treatment of esophageal cancer. Upper mediastinal lymph node dissection is of great value for accurate staging and improving the prognosis of patients. Lymph node dissection along the left recurrent laryngeal nerve is the most challenging procedures in esophageal surgery, and there has been no relevant consensus on the scope and boundary of lymph node dissection. In recent years, with the application of endoscopic technology, especially robotic surgery system in esophagectomy, and the introduction of the concept of superior mediastinal microdissection, the authors have proposed the border of lymph node dissection along the left recurrent laryngeal nerve, so as to achieve precise, radical and standardized dissection. Combined with their own experiences, the authors elaborate on the anatomic boundary, extent and technique of lymph node dissection along the left recurrent laryngeal nerve.

Objective:To investigate the blood-brain barrier (BBB) permeability changes in the deep white matter (DWM) during hypoperfusion caused by asymptomatic cerebral artery stenosis.Methods:The CT perfusion weighted imaging (CTP) images of 36 patients with asymptomatic severe stenosis and unilateral internal carotid artery or middle cerebral artery, admitted to our hospital from January 2017 to April 2020, which revealed the prolongation of contrast medium delayed contrast medium max-time (Tmax), were analyzed. The regions of interest (ROIs) in the DWM of CTP images at the body of lateral ventricle and centrum semiovale, were drawn respectively: the anterior DWM (ROIa), middle DWM (ROIm), and posterior DWM (ROIp) in the stenotic side of maximum intensity projection maps; DWM with normal-appeared Tmax (ROI1), DWM with relatively delayed Tmax (ROI2), and DWM with obviously delayed Tmax (ROI3) in the stenotic side of Tmax maps; and their mirrored ROI on the healthy side. Statistical analysis was used to compare the value differences of Tmax, cerebral blood flow (CBF) and transfer constant (Ktrans) between/among the ROIs.Results:As compared with the mirrored ROI in the healthy side, respectively, the ROIa and ROIm in the stenotic side had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans at the body of lateral ventricle ( P<0.05). As compared with the mirrored ROI in the healthy side, respectively, the ROIa and ROIp in the stenotic side had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans at the centrum semiovale ( P<0.05). As compared with the mirrored ROI in the healthy side, respectively, the ROI2 and ROI3 in the stenotic side had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans at the body of lateral ventricle and centrum semiovale ( P<0.05). In the stenotic side at the body of lateral ventricle, as compared with the mirrored ROIp, the ROIa and ROIm had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans ( P<0.05). In the stenotic side at the body of lateral ventricle and centrum semiovale, as compared with the mirrored ROI1, the ROI2 and ROI3 had significantly prolonged Tmax, significantly decreased CBF, and significantly increased Ktrans ( P<0.05). Conclusion:The BBB permeability of DWM in the regions with delayed contrast medium Tmax is augmented when asymptomatic cerebral artery stenosis causes cerebral hypoperfusion.