1.Pathogenesis of Chronic Obstructive Pulmonary Disease and Modulating Effect of Traditional Chinese Medicine: A Review
Jiyu ZOU ; Tianjiao WANG ; Ningzi ZANG ; Yongming LIU ; Lijian PANG ; Linlin WANG ; Xiaodong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):287-298
Chronic obstructive pulmonary disease (COPD), as a chronic respiratory disease that can be prevented and intervened but cannot be completely cured, has increasing incidence and mortality rates year by year, often complicated by one or more comorbidities. However, there is currently no specific treatment available. Therefore, the healthcare issues related to COPD are urgent and prominent. Traditional Chinese medicine (TCM) delays the progression of COPD through multiple mechanisms, pathways, and targets. As a result, exploring the pathogenesis of COPD and identifying TCM treatment approaches and effective prescriptions are key issues that urgently need to be addressed in clinical practice. In TCM, COPD is categorized into syndromes such as "cough", "asthma", and "lung distension". It is believed that the deficiency in the origin runs through the entire disease. When external pathogens invade, Qi becomes disordered, and phlegm and blood stasis begin to accumulate, leading to an excess condition in the manifestation. Modern medicine research on the pathogenesis of COPD mainly involves aspects such as inflammatory response, oxidative stress, autophagy imbalance, and aging. Studies have found that Chinese medicine monomers, single herbs, and compound prescriptions can improve COPD by inhibiting inflammation, reducing oxidative damage, correcting autophagy, and delaying aging. However, there is no study that intuitively organizes the various pathogenesis mechanisms of COPD and their interrelationships. At the same time, research on the therapeutic effects of TCM on COPD primarily focuses on exploring a single mechanism or pathway, without integrating multiple mechanisms, pathways, and targets. Additionally, there are very few studies that summarize the corresponding relationships between the various pathogenesis mechanisms of COPD and the regulatory effects and signaling pathways of Chinese medicine. This study, for the first time, combines the latest literature in China and abroad to explain the various pathogenesis mechanisms of COPD and their interrelationships using a combination of graphs, text, and tables. It also outlines the signaling pathways, targets, and mechanisms of Chinese medicine monomers, single herbs, and compound prescriptions in regulating COPD, in order to provide new ideas and strategies for the in-depth research and systematic treatment of COPD with TCM.
2.Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma
Xiong GAN ; Xie NAN ; Nie MIN ; Ling RONGSONG ; Yun BOKAI ; Xie JIAXIANG ; Ren LINLIN ; Huang YAQI ; Wang WENJIN ; Yi CHEN ; Zhang MING ; Xu XIUYUN ; Zhang CAIHUA ; Zou BIN ; Zhang LEITAO ; Liu XIQIANG ; Huang HONGZHANG ; Chen DEMENG ; Cao WEI ; Wang CHENG
International Journal of Oral Science 2024;16(2):251-264
Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.
3.Influences of Morin hydrate on pyroptosis of alveolar epithelial cells in rats with chronic obstructive pulmonary disease by inhibiting NLRP3/Caspase-1/IL-1β signaling pathway
Qu ZOU ; Yao OUYANG ; Linlin ZOU ; Dandan FU
Chinese Journal of Immunology 2024;40(10):2052-2057
Objective:To investigate the mechanism of Morin hydrate(MH)on pyroptosis of alveolar epithelial cells in rats with chronic obstructive pulmonary disease(COPD)by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(Caspase-1)/IL-1β signaling pathway.Methods:COPD model rats were estab-lished by smoking method,which were randomly divided into model group(COPD group),low,medium and high doses MH groups(MH-L,MH-M,MH-H groups)(50,100,200 mg/kg)and positive control group(dexamethasone group,DXMS,0.09 mg/kg),another 10 healthy rats were taken as normal control group(NC group).Pulmonary function indexes[tidal volume(TV),forced vital capacity(FVC)and peak expiratory flow rate(PEF)]were measured;HE staining was used to observe pathological changes of lung tissue;pyroptosis of alveolar epithelial cells was observed by immunofluorescence double staining;levels of inflammatory factors in bronchoalveolar lavage fluid(BALF)were detected by ELISA;levels of NLRP3,Caspase-1,gasdermin D(GSDMD)and IL-1β mRNA were detected by RT-qPCR;protein expressions of SP-C,NLRP3,C-Caspase-1,GSDMD,GSDMD-N and IL-1β in lung tissue were detected by Western blot.Results:Compared with COPD group,pathological changes of lung tissue including lumen stenosis,mucus secretion and bronchial epithelial cell necrosis in DXMS group and MH groups were significantly improved,the pulmonary function indexes(TV,FVC,PEF)were increased obviously(P<0.05),and increased in turn in MH-L,MH-M,MH-H groups(P<0.05);levels of TNF-α,IL-6,IL-8,immunofluorescence expressions of NLRP3 and C-Caspase-1,and mRNA levels of NLRP3,Cas-pase-1,GSDMD,IL-1β,protein levels of NLRP3,C-Caspase-1,GSDMD,GSDMD-N and IL-1β were decreased obviously,while SP-C protein expression was gradually increased(P<0.05).Conclusion:MH can inhibit the NLRP3/Caspase-1/IL-1β signaling path-way,the release of inflammatory factors and pyroptosis by it,and alleviate lung pathological changes in COPD rats.
4.Clinical features and stroke etiology in 10 patients with bilateral middle cerebellar peduncle infarctions: a preliminary study
Jiwei JIANG ; Ya'ou LIU ; Xiping GONG ; Linlin WANG ; Wenyi LI ; Xinying ZOU ; Junjie LI ; Jun XU
Chinese Journal of Neurology 2023;56(6):654-660
Objective:To characterize clinical and neuroimaging features, etiologies, and mechanisms of bilateral middle cerebellar peduncle (MCP) infarctions.Methods:Consecutive patients with bilateral MCP infarctions treated in the Beijing Tiantan Hospital, Capital Medical University between January 1, 2020 and April 30, 2022 were enrolled in this retrospective study. The demographic data, vascular risk factors, clincial manifestations and the National Institutes of Health Stroke Scale (NIHSS) scores were collected. Brain diffusion-weighted imaging was used to assess the regions of cerebral infarction, and the extracranial and intracranial segments of the vertebrobasilar artery were evaluated using magnetic resonance angiography, or computed tomography angiography. The stroke etiology and underlying mechanism were evaluated according to the Chinese Ischemic Stroke Subclassification.Results:Ten patients with bilateral MCP infarctions (8 men and 2 women) were analyzed ultimately. The onset age were 51.0-86.0 (64.8±11.4) years. NIHSS scores were 2.0-12.0 (4.9±2.9) points at admission. All patients had vascular risk factors, most of which were hypertension (10 cases) and dyslipoproteinemia (8 cases). The most common clinical manifestations were vertigo (10 cases), followed by ataxia (9 cases) and dysarthria (8 cases). Four cases were isolated bilateral MCP infarctions, while 6 patients were combined with other vertebrobasilar artery infarctions, 4 of which were combined with cerebellar hemisphere infarctions, consistent with the clinical symptoms. The etiology in all patients was large atherosclerosis (severe stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery; 9 cases). Five patients were classified as hypoperfusion/impaired emboli clearance, while 4 patients were considered as artery-to-artery embolism, and 1 was considered as the parent artery (plaque or thrombosis) occluding penetrating artery.Conclusions:Bilateral MCP infarctions are an extremely rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria. Cerebral infarction can be isolated or often combined with cerebellar hemisphere infarction. The etiology was mostly stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery.
5.Modified Wuhutang Alleviates Airway Inflammation and Down-regulates Expression of Muc5AC, STAT3, NF-κB, and NLRP3 in Lung Tissues of RSV-infected Asthmatic Mice
Linlin YU ; Jing WANG ; Ya ZOU ; Weiwei CHENG ; Xiaoping JING
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(19):108-115
ObjectiveTo explore effect of modified Wuhutang on airway inflammation and expression of mucin (Muc) 5AC, signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB), and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in respiratory syncytial virus (RSV)-infected asthmatic mice. MethodSeventy male BALB/c mice of 6-8 weeks old were randomized into normal control (CON), asthma (ovalbumin, OVA), RSV infection-induced asthma (OVA+RSV), high-, medium-, and low-dose (4.08, 2.04, 1.02 g·kg-1·d-1, respectively) modified Wuhutang, and dexamethasone (Dxms, 0.1 g·kg-1d-1) groups (n=10). The model of asthma was established by sensitization and atomization inhalation with OVA. The RSV infection-induced asthma model was established by three consecutive RSV nasal infusions (1.0 × 106 PFU·mL-1, 50 μL). Wuhutang was administrated by gavage, and Dxms by intraperitoneal injection. The CON group was given the same amount of normal saline by gavage. The mice were anesthetized with 2.5% pentobarbital sodium 24 h after the last administration, and then the lung tissue was stained by hematoxylin-eosin (HE) and Van Gieson (VG) for observation of airway inflammation. The immunohistochemical assay was employed to detect the expression of Muc5AC. Western blot was employed to determine the protein levels of phosphorylated (p)-STAT3, STAT3, p-NF-κB, NF-κB, and NLRP3. ResultCompared with the CON group, the OVA group presented airway inflammatory cell infiltration, tissue hyperemia and edema, and collagen fiber deposition. The OVA+RSV group showed severer airway inflammatory cell infiltration and tissue hyperemia and edema than the OVA group. Compared with the OVA+RSV group, modified Wuhutang alleviated the airway inflammatory cell infiltration, tissue hyperemia and edema, and collagen fiber deposition, and the high-dose group had the best performance. Compared with the CON group, the OVA group and the OVA+RSV group showed increased expression level of Muc5AC (P<0.01). Compared with the OVA+RSV group, modified Wuhutang reduced the expression level of Muc5AC, and the reduction was significant in the high-dose group (P<0.05). Compared with the high-dose modified Wuhutang group, Dxms lowered the expression level of Muc5AC (P<0.05). Compared with the CON group, the OVA and OVA+RSV groups showed up-regulated protein levels of p-STAT3, p-NF-κB, and NLRP3 (P<0.05, P<0.01). Compared with the OVA+RSV group, modified Wuhutang down-regulated the protein levels of p-STAT3, p-NF-κB, and NLRP3 (P<0.01). Compared with the high-dose modified Wuhutang group, the Dxms group showed up-regulated levels of p-STAT3, p-NF-κB proteins (P<0.01). ConclusionModified Wuhutang can reduce airway inflammation and down-regulate the expression of Muc5AC, p-STAT3, p-NF-κB, and NLRP3 in RSV-infected asthmatic mice, which suggests that Wuhutang reduces airway inflammation in RSV-infected asthma by regulating the STAT3/NF-κB signaling pathway.
6. Progress of pharmacotherapy for heart failure
Juan PENG ; Yunzeng ZOU ; Linlin FAN ; Ranyi LI ; Xiaoyu LI ; Qianzhou LV
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(4):373-381
Heart failure is the terminal stage of all kinds of heart diseases. Despite the use of a variety of traditional drug standard treatment, the prognosis is still not ideal, and there is an urgent need for the update and improvement of new drugs and treatment methods. In recent years, angiotensin receptor-enkephalase inhibitors (Sacubitril/Valsartan), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), soluble guanoside cyclase agonists (Vericiguat) and myocardial myosin activators omecamtiv mecarbil have been developed successively. SGLT2 inhibitors can improve ventricular load, reduce fibrosis and affect myocardial metabolism. sGC agonists play an anti-heart failure role by enhancing l-ARg-No-SGC-CGMP signaling pathway, improving myocardial and vascular function, reversing ventricular hypertrophy and fibrosis, slowing ventricular remodeling, and reducing ventricular afterload through systemic and pulmonary vasodilation. In addition, fineridone, a novel salt corticosteroid receptor antagonist, has also been reported in clinical studies in the field of heart failure. Therefore, it is the direction and hope for the development of heart failure in the future to select appropriate drugs for different types of patients with heart failure and carry out individualized treatment according to the optimized process of heart failure.
7. Progress of pharmacotherapy for myocardial hypertrophy and cardiac remodeling
Juan PENG ; Yunzeng ZOU ; Ranyi LI ; Linlin FAN ; Xiaoyu LI ; Qianzhou LV
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(4):382-389
Cardiomyopathy is a disease with abnormal myocardial structure and function. For a long time, due to the limited understanding of cardiomyopathies, cardiomyopathies are treated empirically based on symptoms (such as heart failure, arrhythmia, etc.). Over years, with the improvement of diagnosis technology and the discover of disease mechanism, a variety of drugs have been approved, such as tafamidis, patisiran and Inotersen. Many more drugs have completed preliminary safety and efficacy verification and entered Phase III trials. In addition, some cutting-edge technologies are also being developed, such as siRNA drug patisiran, CRISPR/Cas9 gene editing technology drug NTLA-2001, stem cell therapy, etc. This article discusses two cardiac problems that may be caused by cardiomyopathy: myocardial hypertrophy and cardiac remodeling, and introduces the pharmacology and related research of the latest drugs for these diseases.
8.Study on the growth curve of uncorrected visual acuity of children and adolescents with relative safe refractive range
Chinese Journal of School Health 2021;42(6):893-897
Objective:
To analyze the distribution of uncorrected visual acuity in children and adolescents aged 3-18 years with relative safe refractive range, and to develop the growth curve and reference range of uncorrected visual acuity in children and adolescents of different ages, so as to provide reference for formulating the referral threshold for myopia screening practice.
Methods:
Using cluster sampling method, 9 146 children and adolescents aged 3-18 years old in Shanghai were selected for uncorrected visual acuity, cycloplegic refraction, slit lamp and other ophthalmic examinations, and the percentiles and growth curve of uncorrected visual acuity of children and adolescents in the relative safe refractive range were fitted by LMS method. Besides, the area under the ROC curve and the sensitivity and specificity of different cut-off values were analyzed.
Results:
The uncorrected visual acuity was skewed, with a median of 4.8. There were 4 675 individuals with safe refraction, the median of uncorrected visual acuity in which was 4.9. The LMS curve showed that the uncorrected visual acuity increased with age in the lower age group, and gradually stabilized to the best level at the age of 6-10. P 50 was 4.8 in 3-4 years old, 4.9 in 5-8 years old, 5.0 in 9 years old and above. The area under ROC curve of uncorrected visual acuity predicting refractive abnormality increased with age, with the lowest value of 0.55(95%CI=0.50-0.61) at 3 years old and the highest value of 0.95 (95%CI=0.94-0.96) at 12-18 years old. The Youden index was the highest for P25 at 3-6 years old, and the highest for P 10 at 7 years old and above. With the increase of the cut off value, the sensitivity increased and the specificity decreased.
Conclusion
The uncorrected visual acuity increases gradually with age, and reaches the best level after 6-10 years old. The screening effect of uncorrected visual acuity predicting refractive abnormality increased with age. It is suggested that the referral threshold of children and adolescents with abnormal uncorrected visual acuity should be set according to their ages, and P 25-P 75 can be selected according to the screening purposes.
9.Development and psychometric test of discrimination experience questionnaire for HIV/acquired immunodeficiency syndrome patients
Yuanbin CUI ; Hui TAN ; Linlin XIE ; Zheng ZHU ; Shuyu HAN ; Jian PENG ; Luoluo ZOU ; Lin WANG ; Yan HU
Chinese Journal of Practical Nursing 2021;37(25):1926-1932
Objective:To develop the discrimination experience questionnaire for HIV/acquired immunodeficiency syndrome(AIDS) patients and test the reliability and validity of the questionnaire.Methods:Based on the literature review and semi-structured interviews to clarify the operational definition of discrimination for HIV/AIDS and develop the item pool. The questionnaire was developed though 2 rounds Delphi consultation and a pilot test. A total of 410 HIV/AIDS patients in Shanghai Public Health Clinical Center of Fudan University from June to December 2020 were selected to investigate the questionnaire, item analysis was used to screen items. SPSS 22.0 software was used for reliability test and exploratory factor analysis, the AMOS 21.0 software was used for confirmatory factor analysis to test the reliability and validity of the questionnaire.Results:The questionnaire consisted 2 dimensions(external discrimination and internal discrimination) and 10 items. Exploratory factor analysis showed that two common factors were extracted from the frequency of discrimination and the degree of negative psychological impact of discrimination experience on patients, and the cumulative variance contribution rates were 48.367% and 55.403%, respectively. The confirmatory factor analysis on the frequency of discrimination showed that Chi square degree of freedom ratio ( χ2/ df) was 2.831, P<0.05, root mean square of approximation error (RMSEA) was 0.093, goodness of fit index (GFI) was 0.928, comparative fit index (CFI) was 0.925, incremental fit index (IFI) was 0.926; the confirmatory factor analysis on the negative psychological impact of discrimination experience on patients showed that χ2/ df was 1.740, P<0.05; RMSEA was 0.076, GFI was 0.925, CFI was 0.936, IFI was 0.938. The content validity of the questionnaire was 0.9. The Cronbach α coefficientof questionnaire was 0.811, and the test-retest coefficient was 0.862 ( P<0.01). Conclusions:The discrimination experience questionnaire for HIV/AIDS patients has good reliability and validity, and it can be used to measure the discrimination for HIV/AIDS patients.
10.Research progress in the application of dopa-inspired compounds to improve the dentin-resin bonding
Linlin YAN ; Zhimin ZHANG ; Yuanhang ZHAO ; Hong ZHAO ; Xinying ZOU ; Jiazhuo SONG ; Xin LIU ; Hong ZHANG
Chinese Journal of Stomatology 2021;56(10):1040-1044
Mussle foot protein has a main component which is named dopa. Dopa can be used to promote a relatively firm adhesion of mussels to the surface of solid materials through forming dihydrogen bonds, π-π/π-cation bonds and chelating metals,etc. To exploit these interactions, there is the opportunity to apply dopa-inspired compounds to improve the dentin-resin bonding. The current review provides valuable information concerning the mechanism of adhesion mediated by mussel foot protein and describes the application of dopa-inspired compounds in the dentin-resin bonding. The article provides novel information for future research in optimization of the properties of dentin-resin bonding.


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