ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Based on the target recognition ability of split aptamer and intelligent analytical capability of molecular logic gate,in this work,two split aptamers were integrated into"AND"logic gate to construct a novel ortho-nucleic acid fluorescence sensor for simultaneous detection of thrombin and myoglobin.When there was one target,the response of the signal was only a single fluorescence output signal,which was used as an evaluation standard for early low-risk judgment.When two targets coexisted,the split aptamer bound to the target to form a ternary complex and led to the head and tail ortho-nucleic acid effect respectively,and triggered the G4 chain to enhance the fluorescence signal of thioflavin T and the fluorescence signal quenching of Cyanine 3,which could be used as an evaluation criterion for early high-risk judgement.Under the optimal conditions,the linear range for detection of thrombin was 3-200 nmol/L,with a correlation coefficient of 0.9931 and a detection limit of 0.97 nmol/L,and the linear range for detection of myoglobin was 6-400 nmol/L,with a correlation coefficient of 0.9933,and a detection limit of 2.14 nmol/L.The method was applied to simultaneous determination of thrombin and myoglobin in clinical serum samples,and the recoveries were 85.4%-118.3%and 85.8%-119.9%,respectively,with relative standard deviations of less than 6.5%.Compared with the standard method,the relative error range was from-8.8%to 5.6%.In addition,the logical diagnosis results of 4 serum samples were high-risk of acute myocardial infarction in 2 cases and low-risk in 2 cases.The ″AND″ logic gate ortho-nucleic acid fluorescence sensing method showed many advantages such as high selectivity,rapidity,accuracy and simultaneous detection,which offered important reference for early diagnosis of acute myocardial infarction,and also provided a general detection design strategy and platform for simultaneous detection of biomarkers.

Objective:To investigate the effects of Zhuanggu Zhitong Capsules on JNK signaling molecules and their phosphorylated proteins in postmenopausal osteoporosis model female mice.Methods:The rats were divided into sham-operation group, blank group, model group, positive drug group, and Zhuanggu Zhitong Capsules group according to the random number table method, with 10 rats in each group. The model group, the positive drug group and the Zhuanggu Zhitong Capsules group were prepared by bilateral ovarian detomy to prepare a female mouse model of postmenopausal osteoporosis. The positive drug group was given 0.9 mg/kg of alendronate sodium, the Zhuanggu Zhitong Capsules group was given was Zhuanggu Zhitong Capsules 1.944 g/kg for gavage, and the blank group, sham-operation group, and model group were given the same volume of normal saline for gavage, once a day for a total of 13 weeks. Rat vaginal exfoliated cells were stained with Wright's staining; serum Omentin-1 and 25(OH)D 3 levels were determined by ELISA; renal tissue and femoral structure were observed by HE staining; JNK and p-JNK protein expressions were detected by immunohistochemical staining; JNK mRNA levels were detected by PCR. Results:Compared with the model group, the serum levels of 25(OH)D3 and Omentin-1 in the Zhuanggu Zhitong Capsules group and the positive drug group increased ( P<0.01), the mean gray values of JNK and p-JNK protein in bone and kidney tissues decreased ( P<0.01), and the mRNA levels of JNK in bone and kidney tissues decreased ( P<0.01). Conclusion:Zhuanggu Zhitong Capsules can effectively improve the bone microstructure of postmenopausal osteoporotic rats, and its mechanism may be related to the regulation of JNK signaling pathway.

ObjectiveTo evaluate the effectiveness and safety of Sufei Pingchuan Formula （肃肺平喘方） in the treatment of bronchiectasis with airflow limitation， phlegm-heat obstructing the lung， and lung-spleen qi deficiency syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 72 patients with stable bronchiectasis with airflow limitation of phlegm-heat obstructing the lung and lung-spleen qi deficiency syndrome were randomly divided into treatment group and control group， with 36 cases in each group. On the basis of regular inhalation of tiotropium bromide inhalation spray， the treatment group was given Sufei Pingchuan Formula granules， and the control group was given Sufei Pingchuan Formula granule simulant. The course of treatment in both groups was 12 weeks. The pulmonary function of both groups before and after treatment was observed， specifically focusing on forced expiratory volume in one second （FEV1）； the modified British Medical Research Council （mMRC） dyspnea scale， 24-hour sputum volume， COPD assessment test （CAT）， and traditional Chinese medicine （TCM） syndrome scores were assessed before treatment and after 4， 8， and 12 weeks of treatment； acute exacerbations were recorded at weeks 4， 8， and 12； additionally， changes in routine blood tests， urinalysis， liver and kidney function， and adverse events were monitored before and after treatment. ResultsAfter treatment， 4 patients in the treatment group and 6 in the control group dropped out. After 12 weeks of treatment， FEV1 increased in both groups compared to pre-treatment levels （P＜0.05）， but the difference between groups was not statistically significant （P＞0.05）. Compared to before treatment， the treatment group showed a reduction in mMRC scores after 12 weeks （P＜0.05） and a decrease in 24-hour sputum volume， CAT scores， and TCM syndrome scores at weeks 4， 8， and 12 （P＜0.05）. In the control group， 24-hour sputum volume decreased after 12 weeks （P＜0.05）， and TCM syndrome scores decreased at weeks 8 and 12 （P＜0.05）. Compared to the control group， the treatment group showed a greater reduction in mMRC scores at week 12 （P＜0.05）， a decrease in 24-hour sputum volume and TCM syndrome scores at weeks 4， 8， and 12 （P＜0.05）， and lower CAT scores at weeks 8 and 12 （P＜0.05）. The frequency and number of acute exacerbations in the treatment group were significantly lower than those in the control group at week 12 （P＜0.05）. No severe adverse events occurred in either group. ConclusionSufei Pingchuan Formula can improve the pulmonary function FEV1， the severity of dyspnea， reduce 24-hour sputum volume and frequent acute exacerbations， and improve the quality of life in patients with bronchiectasis and airflow limitation， with good safety.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

The zebrafish model has attracted much attention due to its strong reproductive ability, short research cycle, and ease of maintenance. It has always been an important vertebrate model system, often used to carry out human disease research. Its motor behavior features have the advantages of being simpler, more intuitive, and quantifiable. In recent years, it has received widespread attention in the study of traditional Chinese medicine(TCM)for the treatment of sleep disorders, neurodegenerative diseases, fatigue, epilepsy, and other diseases. This paper reviews the characteristics of zebrafish motor behavior and its applications in the pharmacodynamic verification and mechanism research of TCM extracts, active ingredients, and TCM compounds, as well as in active ingredient screening and safety evaluation. The paper also analyzes its advantages and disadvantages, with the aim of improving the breadth and depth of zebrafish and its motor behavior applications in the field of TCM research.
Zebrafish/physiology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Drug Evaluation, Preclinical/methods* ; Animals ; Sleep Wake Disorders/physiopathology* ; Epilepsy/physiopathology* ; Neurodegenerative Diseases/physiopathology* ; Fatigue/physiopathology* ; Behavior, Animal/physiology* ; Motor Activity/physiology*

Objective:To observe the pathological changes of myocardial tissue under differentdegrees of coronary atherosclerotic le-sions,to measure the expression levels of proteins associated with the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway in coronary arteries,and to investigate the role of cGAS-STING in the development and progression of coronary heart disease.Methods:Eligible cases of coronary heart disease and control cases were selected and divided into control group with normal coronary arteries and grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups.HE staining was used to observe and evaluate the pathological conditions of coronary arteries,Western blotting was used to measure the expression levels of downstream pro-teins of the cGAS-STING pathway in coronary tissue,and ELISA was used to measure the levels of inflammatory factors in coronary tis-sue.A correlation analysis was performed to investigate the correlation of the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors with the development and progression of coronary heart disease.Results:Mi-croscopic examination showed that compared with the control group,the other four groups had varying degrees of pathological changes such as vascular wall thickening and luminal stenosis,with a gradual increase in the degree of stenosis from grade Ⅰ to grade Ⅳ coronary lesions.Compared with the control group,the grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups had significant increases in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors in coronary tis-sue,with a trend of increase from grade Ⅰ to grade Ⅳ coronary le-sions.The expression levels of downstream proteins of the cGAS-STING signaling pathway in coronary tissue were positively correlated with the development and progression of coronary heart disease(cGAS:r=0.927,P<0.001;p-Sting:r=0.889,P<0.001;p-TBK1:r=0.910,P<0.001;p-IRF3:r=0.936,P<0.001;IFN-1:r=0.936,P<0.001;TNF-α:r=0.945,P<0.001;IL-1β:r=0.962,P<0.001;IL-6:r=0.933,P<0.001).Conclusion:There are significant differences in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors,and this signaling pathway may be a potential target for the treatment of coronary heart disease.

Objective To employ three dimensional high-resolution vessel wall magnetic resonance imaging(3D hr-VW-MRI)for analyzing the imaging characteristics of posterior circulation non-stenotic intracranial atherosclerotic plaque and to discuss its diagnostic value in identifying culprit plaques.Methods Ninety-three patients(age[62.94±9.70]years old,67 males,26 females)with non-stenotic atherosclerosis in our hospital from Jan.2019 to Jan.2021 were retrospectively recruited.The imaging features of plaques,including luminal area,maximum wall thickness and minimum wall thickness at the most stenotic site,stenosis rate,plaque burden,remodeling index,eccentricity index,enhancement ratio at the most stenotic site,and intraplaque hemorrhage,were measured based on T1-weighted imaging(T1WI)and contrast-enhanced T1WI.The culprit plaque was defined as a lesion arising from the responsible vascular supply area to a fresh infarction on the diffusion weighted imaging(DWI)and T2 fluid attenuated inversion recovery(T2-FLAIR)images with accompanying ischemic stroke/transient ischemic attack(TIA).A plaque was considered to be a nonculprit plaque when it occurred in patients with presumed ischemic stroke/TIA,but without an infarct on DWI and T2-FLAIR.Results Sixty-one culprit plaques and 32 non-culprit plaques were analyzed.The proportions of patients with hyperlipidemia,National Institutes of Health stroke scale(NIHSS)score,narrowest plaque enhancement rate,and incidence of intraplaque hemorrhage in the culprit plaque group were significantly higher than those in the non-culprit plaque group(all P＜0.05).Multivariate logistic regression analyses showed that NIHSS score(odds ratio[OR]=1.799,95％confidence interval[CI]1.303-2.484,P＜0.001),enhancement ratio(OR=1.076,95％CI 1.027-1.128,P=0.002)and intraplaque hemorrhage(OR=30.708,95％CI 2.563-367.925,P=0.007)were associated with plaque type.Conclusion NIHSS score,enhancement ratio at the most stenotic site,and intraplaque hemorrhage are independent risk factors for culprit plaques in patients with posterior circulation non-stenotic intracranial atherosclerotic disease.These indicators may help identify such culprit plaques and could be used to screen individuals with plaques having these characteristics,thereby providing a basis for early preventive interventions.

Objective To explore the correlation between stroke etiology and clinical and imaging features in patients with acute ischemic stroke(AIS)due to large vessel occlusion treated by intravascular thrombectomy.Methods A total of 213 patients with AIS and endovascular embolectomy in our hospital from Oct.2016 to Jun.2018 were enrolled retrospectively.According to the etiological classification criteria of Trial of Org 10172 in Acute Stroke Treatment(TOAST),there were 116 cases of cardioembolism and 97 cases of non-cardioembolism.Multivariate logistic regression analysis was used to screen the clinical and imaging characteristics for identifying cardioembolism and non-cardioembolism.Results Compared with non-cardioembolism AIS,cardioembolism AIS was associated with higher NIHSS scores(adjusted odds ratio[OR]=1.09,95%confidence interval[95%CI]1.01-1.18,P=0.02),atrial fibrillation(adjusted OR=76.46,95%CI 26.75-218.51,P＜0.01),absence of hypertension(adjusted OR=0.32,95%CI 0.12-0.84,P=0.02),antiplatelet drug use(adjusted OR=5.03,95%CI 1.22-20.63,P=0.03),shorter onset-to-puncture time(adjusted OR=0.998,95%CI 0.996-1.000,P=0.04),and presence of hyperdense artery sign(HAS)(adjusted OR=4.45,95%CI 1.47-13.49,P=0.01).Conclusion There are some differences in clinical and imaging characteristics between patients with cardioembolism and non-cardioembolism AIS.The occurrence of HAS suggests a higher probability of cardioembolism in AIS patients.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL