As an innovative dosage form, traditional Chinese medicine(TCM) dry powder inhalers have emerged as a focal point in the research and development of new preparations due to its high efficiency, safety, and bioavailability. This paper systematically reviewed the relevant literature and patents associated with TCM dry powder inhalers to analyze the origins and the current research and development status. Furthermore, this paper probed into the research and development ideas of TCM dry powder inhalers regarding clinical positioning, prescription screening, and druggability. Additionally, the paper thoroughly analyzed the technical barriers in druggability studies and elaborated on corresponding research techniques and coping measures. Furthermore, it emphasized the need for improved regulations and policies governing TCM dry powder inhalers, advocated for strengthened oversight, and called for the establishment of a scientific quality evaluation system. Measures such as promoting production-education-research collaboration, enhancing personnel training, and fostering international exchanges were proposed to provide a scientific and systematic reference for the future research, development, and application of TCM dry powder inhalers, thereby facilitating the rapid modernization of TCM.
Humans ; Dry Powder Inhalers/trends* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/instrumentation* ; Administration, Inhalation

The chemical constituents of Commiphora myrrha was investigated by column chromatography on silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by comprehensive spectroscopic methods including UV, IR, MS, NMR, as well as ECD calculation. Seven compounds were isolated from the dichloromethane-soluble fraction of C. myrrha and their structures were identified as(1S,2R,4S,5R,8S)-guaiane-2-hydroxy-7(11),10(15)-dien-6-oxo-12,8-olide(1), commipholide E(2), myrrhterpenoid H(3), myrrhterpenoid I(4), myrrhterpenoid E(5), 2α-methoxy-8α-hydroxy-6-oxogermacra-1(10),7(11)-dien-8,12-olide(6), 8,12-epoxy-1α,9α-hydroxy-eudesma-7,11-diene-6-dione(7). Compound 1 was a new compound and named myrrhterpenoid P. Compound 7 was isolated from Commiphora genus for the first time. Compounds 2, 5, and 6 significantly inhibited nitric oxide(NO) production in LPS-stimulated RAW264.7 cells, with IC_(50) values of(49.67±4.16),(40.80±1.27),(47.22±0.87) μmol·L~(-1), respectively [indomethacin as the positive control, with IC_(50) value of(63.92±2.60) μmol·L~(-1)].
Commiphora/chemistry* ; Animals ; Mice ; Resins, Plant/chemistry* ; Sesquiterpenes/isolation & purification* ; Molecular Structure ; Nitric Oxide ; Macrophages/metabolism* ; RAW 264.7 Cells ; Drugs, Chinese Herbal/pharmacology*

This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

Objective To investigate the characteristics of thickness changes in peripapillary retinal nerve fiber layer(pRNFL)and identify related risk factors in patients with Moyamoya disease(MMD).Methods A retrospective study was conducted on 150 MMD patients(150 eyes)aged 6-65 years admitted to the Neurosurgery Department of the Fifth Medical Center,Chinese PLA General Hospital from May 2016 to December 2023(observation group),and 150 age-matched healthy volunteers(150 eyes)from the hospital's ophthalmology outpatient department(control group).Both groups were subdivided into pediatric(≤18 years),young adult(18-40 years),and middle-aged(40-65 years)subgroups.The pRNFL thickness in four quadrants was measured by optical coherence tomography(OCT):superior(pRNFL-Sup),inferior(pRNFL-Inf),nasal(pRNFL-Nas),temporal(pRNFL-Tmp),and average thickness(pRNFL-Avg).General clinical data and pRNFL thickness were compared between two groups.Univariate and multivariate logistic regression analyses were performed to identify risk factors for pRNFL thinning in MMD patients.The cohort was randomly divided into training(n=210)and validation(n=90)sets at a 7:3 ratio.A predictive model for pRNFL thinning in MMD patients was constructed based on logistic regression results.Model performance was evaluated using the area under the receiver operating characteristic curve(AUC),and clinical utility was assessed via decision curve analysis.Results Compared with control group,MMD patients exhibited significantly reduced pRNFL-Avg,pRNFL-Sup,pRNFL-Tmp,and pRNFL-Inf thickness(P<0.05 or P<0.001),while pRNFL-Nas showed no significant difference(P>0.05).In the pediatric subgroup,pRNFL-Avg and pRNFL-Inf were thinner(P<0.05).In the young adult subgroup,pRNFL-Avg and pRNFL-Sup were reduced(P<0.001 or P<0.05).In the middle-aged subgroup,pRNFL-Avg,pRNFL-Sup,pRNFL-Inf,and pRNFL-Tmp were all thinner(P<0.05 or P<0.001).Multivariate logistic regression identified visual field defects(OR=15.28,95%CI 2.95-79.10),disease duration(OR=1.11,95%CI 1.05-1.18),and the number of involved cerebral vessels(OR=1.49,95%CI 1.01-2.22)as independent risk factors for pRNFL thinning.The predictive model achieved AUC of 0.94(95%CI 0.91-0.97)and 0.95(95%CI 0.91-0.99)in the training and validation sets,respectively.Decision curve analysis confirmed the model's favorable clinical net benefit.Conclusion Thinning of pRNFL was observed in Moyamoya disease patients with visual field defects,disease duration,and cerebral vascular involvement identified as independent risk factors for pRNFL atrophy.

Objective:To investigate the morphological and ultrastructural differences between normal and round-headed sperm and the outcomes of assisted reproduction in patients with partial globozoospermia.Methods:We collected clinical information and semen samples from 6 cases of partial globozoospermia confirmed in our hosptials from March 2023 to March 2024,performed Diff-Quik staining of the samples,observed the sperm morphology under the light microscope and transmission electron microscope,compared the ultrastructures between round-headed and normal spermatozoa,and analyzed the clinical outcomes of assisted reproduction in the pa-tients.Results:Under the light microscope,the the round-headed sperm had no acrosomal structure,some with tail abnormalities;while under the transmission electron microscope,they exhibited dissolved plasma membrane,acrosomal absence,small acrosomes,nucleoplasmic granulation,huge central vacuoles,swelling,absence or irregular arrangement of mitochondria in the neck,and disor-ganized or missed 9+2 microtubules in the tail.All the 6 patients underwent intracytoplasmic sperm injection(ICSI),and 1 of them achieved pregnancy.Conclusion:The sperm organelle is morphologically damaged and ultrastructurally abnormal in some patients with partial globozoospermia,which may be a key factor for their infertility,and ICSI can help some of them to achieve fertility.

Background::Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac.Methods::Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses.Results::In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V 100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V 100% relative percentages of all scans was 99.60% ± 1.18%. The median V 29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion::UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR–based dosimetry analysis.Clinical trial registration::Chinese Clinical Trial Registry ChiCTR2000033382.

Background::Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac.Methods::Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses.Results::In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V 100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V 100% relative percentages of all scans was 99.60% ± 1.18%. The median V 29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion::UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR–based dosimetry analysis.Clinical trial registration::Chinese Clinical Trial Registry ChiCTR2000033382.

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.
Humans ; COVID-19 ; Algorithms ; Databases, Factual ; Prescriptions ; Plant Extracts

Chronic obstructive pulmonary disease （COPD） is a common and frequently-occurring disease of the respiratory system， characterized by persistent respiratory symptoms and airflow restriction， which is prone to attack repeatedly and affect patients' quality of life seriously. At present， the combination of bronchodilators and inhaled corticosteroids is commonly used in clinic. Although these drugs can alleviate the symptoms of COPD patients， there are certain limitations of the difficulty in controlling the course of the disease effectively and reversing the decline of patients' lung function. Therefore， searching for safer and more effective therapeutic drugs has become a hot research topic nowadays. Traditional Chinese medicine （TCM） has remarkable curative effects and advantages in the prevention and therapy of COPD recently. Based on the increasing research and application of the active components of TCM in the therapy of COPD， studies on their pharmacodynamic mechanism are also more in depth. More and more studies have found that the active components of TCM can treat COPD patients effectively， and the mechanism involved mainly includes the anti-inflammatory， the antioxidant， and the inhibition of apoptosis. By searching and screening the domestic and foreign literatures on the treatment of COPD with the active components of TCM in recent years， the active components of TCM including flavonoids， terpenoids， phenols and saponins have been studied as the research objects， and their effects in improving the pulmonary function and oxidative stress， relieving inflammation and inhibiting apoptosis are expounded. Besides， the mechanism of action， signaling pathways and index molecules have been emphatically summarized， in order to provide the ideas for the clinical therapy and the basic research of COPD.