ObjectiveTo observe the clinical efficacy of modified Jinwei Guben Decoction （金卫固本汤， MJGD） combined with Bailing Capsule （百令胶囊， BC） in the treatment of chronic obstructive pulmonary disease （COPD） patients in the stable stage with qi deficiency， blood stasis and phlegm obstruction syndrome， in addition to conventional western medicine treatment. MethodsA total of 102 patients with stable COPD and qi deficiency， blood stasis， and phlegm obstruction syndrome were included in the study. According to the patients'preferences， they were divided into treatment group （49 cases） and control group （53 cases）. The control group received conventional western medicine treatment， while the treatment group was given MJGD （1 dose daily） combined with BC （2.0 g each time， three times a day） additionally. The treatment period was 3 months， and the patients were followed up for 1 year after the treatment. The acute exacerbation frequency （mild， moderate， severe） before treatment， during treatment， at 6-month follow-up， and at 1-year follow-up was compared between groups. Additionally， the lung function indicators such as FEV₁， FEV₁%pred， FVC， and FEV₁/FVC ratio， traditional Chinese medicine （TCM） syndrome scores， modified British Medical Research Council （mMRC） dyspnea scale， and the COPD Assessment Test （CAT） scores before and after treatment were compared. A logistic regression model was constructed to analyze the impact of MJGD combined with BC on clinical efficacy. ResultsFour patients dropped out from the treatment group and eight from the control group， leaving 45 patients of each group for statistical analysis. The number of mild and moderate acute exacerbations in the treatment group was lower than that in the control group during the treatment period， at 6-month follow-up and within 1 year of follow-up （P＜0.05） .The number of severe acute exacerbations was only lower in the treatment group than in the control group at 6-month follow-up （P＜0.05）. Compared with that before treatment， the number of acute exacerbations of all degrees in the treatment group was significantly reduced within 1 year of follow-up （P＜0.05），while only the number of mild acute exacerbations in the control group was significantly reduced within 1 year of follow-up （P＜0.05）. The treatment group showed significant improvement in FEV₁ and FEV₁%pred and FEV₁/FEV， while the control group showed a significant decline in FEV₁ and FVC （P＜0.05）. After treatment， both groups showed significant reductions in TCM syndrome scores， including coughing， sputum， wheezing， chest tightness， shortness of breath， and fatigue， as well as mMRC and CAT scores （P＜0.05）， with the treatment group having significantly lower scores than the control group （P＜0.05）. The overall clinical effective rate of in the treatment group was 93.33% （42/45）， significantly higher than that of the control group， 75.56% （34/45， P＜0.05）. Multivariate logistic regression analysis showed that the use of MJGD combined with BC （OR = 4.68， 95%CI： 1.15 - 19.09， P = 0.03） was positively correlated with clinical efficacy. ConclusionsIn addition to conventional western medicine treatment， the combination of MJGD and BC can reduce the frequency of acute exacerbations， delay the decline of lung function， improve clinical symptoms， and significantly enhance the clinical efficacy in patients with stable COPD and qi deficiency， blood stasis， and phlegm obstruction syndrome.

ObjectiveTo study the effect of Jinwei Pingchuan decoction combined with conventional Western medicine on the number of acute exacerbations， lung function， and clinical symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease （COPD） with phlegm-heat obstruction in lung syndrome. MethodsA non-randomized controlled trial was conducted to include 60 patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. Patients were divided into a treatment group and a control group based on whether they received Jinwei Pingchuan decoction， with 30 patients in each group. The treatment group received Jinwei Pingchuan decoction combined with conventional Western medicine therapy， while the control group received conventional Western medicine therapy alone. Both groups received treatment for 7 days. The number of acute exacerbations and lung function indices were followed up and recorded before treatment and three months after treatment. The following outcomes were observed before and after treatment： the number of acute exacerbations， lung function indices （forced expiratory volume in one second ［FEV₁］， percentage of predicted value ［FEV₁%pred］， forced vital capacity ［FVC］， and FEV₁/FVC ratio）， the degree of acute exacerbation， TCM syndrome score， COPD assessment test （CAT） score， modified British Medical Research Council Dyspnea Questionnaire （mMRC） score， C-reactive protein （CRP）， and white blood cell （WBC） count. ResultsAfter 3 months of follow-up， the treatment group showed a significant reduction in the number of acute exacerbations compared with the pre-treatment values （P<0.05）. After treatment， the treatment group had fewer acute exacerbations than the control group （P<0.05）. The degree of acute exacerbation in the treatment group improved significantly compared with the pre-treatment values （P<0.05）. After treatment， the degree of acute exacerbation in the treatment group was improved compared to the control group （P<0.05）. Regarding lung function， FEV₁， FEV₁%pred， FVC， and FEV₁/FVC ratio increased significantly in the treatment group compared with the pre-treatment values （P<0.05）， and similar improvements were observed in the control group （P<0.05）. After treatment， FEV₁ and FVC were higher in the treatment group than the control group （P<0.05）. Regarding TCM syndrome scores， the scores for individual symptoms such as wheezing， cough， expectoration， chest tightness， shortness of breath， and fatigue， as well as the total score， decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）. In the control group， the scores for cough， expectoration， chest tightness， fatigue， and palpitation， as well as the total score， also decreased （P<0.05）. After treatment， the treatment group showed significantly lower scores for wheezing， cough， chest tightness， shortness of breath， and the total score than the control group （P<0.05）. Regarding the CAT score， the scores for cough， expectoration， chest tightness， climbing stairs， going out， activity， and energy， as well as the total score， decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）. In the control group， the scores for cough， expectoration， chest tightness， sleep， energy， and the total score decreased （P<0.05）. After treatment， the treatment group showed significantly lower scores for cough， expectoration， chest tightness， activity， and going out than the control group （P<0.05）. Regarding the mMRC score， CRP level， and WBC count， all these parameters decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）， and similar reductions were observed in the control group （P<0.05）. ConclusionJinwei Pingchuan decoction can reduce the number of acute exacerbations and the degree of acute exacerbation in patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. It also improves lung function and symptoms such as cough and chest tightness， thereby enhancing the quality of life of patients.

ObjectiveTo study the effect of Jinwei Pingchuan decoction combined with conventional Western medicine on the number of acute exacerbations， lung function， and clinical symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease （COPD） with phlegm-heat obstruction in lung syndrome. MethodsA non-randomized controlled trial was conducted to include 60 patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. Patients were divided into a treatment group and a control group based on whether they received Jinwei Pingchuan decoction， with 30 patients in each group. The treatment group received Jinwei Pingchuan decoction combined with conventional Western medicine therapy， while the control group received conventional Western medicine therapy alone. Both groups received treatment for 7 days. The number of acute exacerbations and lung function indices were followed up and recorded before treatment and three months after treatment. The following outcomes were observed before and after treatment： the number of acute exacerbations， lung function indices （forced expiratory volume in one second ［FEV₁］， percentage of predicted value ［FEV₁%pred］， forced vital capacity ［FVC］， and FEV₁/FVC ratio）， the degree of acute exacerbation， TCM syndrome score， COPD assessment test （CAT） score， modified British Medical Research Council Dyspnea Questionnaire （mMRC） score， C-reactive protein （CRP）， and white blood cell （WBC） count. ResultsAfter 3 months of follow-up， the treatment group showed a significant reduction in the number of acute exacerbations compared with the pre-treatment values （P<0.05）. After treatment， the treatment group had fewer acute exacerbations than the control group （P<0.05）. The degree of acute exacerbation in the treatment group improved significantly compared with the pre-treatment values （P<0.05）. After treatment， the degree of acute exacerbation in the treatment group was improved compared to the control group （P<0.05）. Regarding lung function， FEV₁， FEV₁%pred， FVC， and FEV₁/FVC ratio increased significantly in the treatment group compared with the pre-treatment values （P<0.05）， and similar improvements were observed in the control group （P<0.05）. After treatment， FEV₁ and FVC were higher in the treatment group than the control group （P<0.05）. Regarding TCM syndrome scores， the scores for individual symptoms such as wheezing， cough， expectoration， chest tightness， shortness of breath， and fatigue， as well as the total score， decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）. In the control group， the scores for cough， expectoration， chest tightness， fatigue， and palpitation， as well as the total score， also decreased （P<0.05）. After treatment， the treatment group showed significantly lower scores for wheezing， cough， chest tightness， shortness of breath， and the total score than the control group （P<0.05）. Regarding the CAT score， the scores for cough， expectoration， chest tightness， climbing stairs， going out， activity， and energy， as well as the total score， decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）. In the control group， the scores for cough， expectoration， chest tightness， sleep， energy， and the total score decreased （P<0.05）. After treatment， the treatment group showed significantly lower scores for cough， expectoration， chest tightness， activity， and going out than the control group （P<0.05）. Regarding the mMRC score， CRP level， and WBC count， all these parameters decreased significantly in the treatment group compared with the pre-treatment values （P<0.05）， and similar reductions were observed in the control group （P<0.05）. ConclusionJinwei Pingchuan decoction can reduce the number of acute exacerbations and the degree of acute exacerbation in patients with acute exacerbation of COPD with phlegm-heat obstruction in lung syndrome. It also improves lung function and symptoms such as cough and chest tightness， thereby enhancing the quality of life of patients.

ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）-hypoxia inducible factor-1α/vascular endothelial growth factor A （HIF-1α/VEGFA） signaling pathway in diabetic retinopathy （DR） rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group， while the remaining 53 rats were fed a high-sugar， high-fat diet combined with low-dose streptozotocin （STZ） intraperitoneal injection to establish a type 2 diabetes mellitus （T2DM） rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model， low-dose， medium-dose， and high-dose groups of Huayu Mingmu prescription （9.29， 18.57， 37.14 g·kg^-1）， and a calcium dobesilate group （0.16 g·kg^-1）， with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography， and pathological changes in retinal tissue were evaluated using hematoxylin-eosin （HE） staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff （PAS） staining. Immunofluorescence （IF） was used to detect the expression of VEGFA and angiopoietin-2 （Ang-2） in retinal tissue. Western blot was employed to detect the protein expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. ResultsCompared with the normal group， the model group exhibited significant pathological changes in retinal tissue， including the appearance of acellular capillaries， as well as significant endothelial cell （E） proliferation and pericyte （P） loss （P<0.01）. The E/P was significantly elevated （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly increased （P<0.01）， and the expression of Ang-2 protein was significantly elevated （P<0.01）. In contrast， retinal tissue in the treatment groups showed alleviated pathological changes， with reduced endothelial cell proliferation and pericyte loss （P<0.05， P<0.01）. Among the treatment groups， the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly reduced （P<0.05， P<0.01）， and the expression of Ang-2 protein was significantly decreased （P<0.01）. ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats， delay the progression of DR， and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

OBJECTIVE To investigate the efficacy and safety of tirofiban for early neurological deterioration in patients with acute ischemic stroke. METHODS A total of 126 patients with early neurological deterioration of acute ischemic stroke who were admitted to the Department of Neurology， Heji Hospital Affiliated to Changzhi Medical College from January 2022 to December 2023 were selected and divided into observation group and control group according to random number table method， with 63 cases in each group. All patients received standardized treatment such as lipid-lowering and blood pressure-lowering therapy. Based on the standard treatment， patients in the control group additionally took Aspirin enteric-coated tablets 100 mg+Clopidogrel bisulfate tablets 75 mg orally （once a day， for 14 consecutive days）. The patients in the observation group received Tirofiban hydrochloride and sodium chloride injection based on the standardized treatment [first intravenous infusion of 0.40 μg/（kg·min） for 30 min， and then continuous intravenous infusion of 0.10 μg/（kg·min） for 47.5 h]； subsequently， patients were given Aspirin enteric-coated tablets （100 mg） and Clopidogrel bisulfate tablets （75 mg） once a day for 14 consecutive days. The clinical efficacy， the National Institutes of Health Stroke Scale （NIHSS） score， modified Rankin Scale （mRS） score， and hemorheological indexes before and after treatment were compared between the two groups， and the adverse reactions were recorded. RESULTS The total effective rate （87.30%） of the observation group was significantly higher than that of the control group （71.43%） （P＜0.05）. NIHSS scores of the two groups at 1st， 7th and 14th day after treatment， the mRS score at 90th day after treatment， and the platelet aggregation rate， whole blood viscosity， plasma viscosity and fibrinogen at 14th day after treatment were significantly lower than those before treatment in the same group， and the observation group was significantly lower than the control group at the same period （P＜0.05）. The total incidences of adverse reactions such as nausea， headache， fever， gastrointestinal bleeding， oral and nasal mucosal bleeding and thrombocytopenia in both groups of patients were 28.57% respectively， with no statistically significant difference （P＞0.05）. CONCLUSIONS For patients with early neurological deterioration in acute ischemic stroke， the addition of tirofiban can accelerate the recovery of neurological function， improve blood hyperviscosity and platelet aggregation， and improve the prognosis of patients with good safety.

As people's living standards improve， the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B （NF-κB） in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors， so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer， and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine （TCM） treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad， it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation， oxidative stress， and energy metabolism， and it is involved in mediating inflammation， pancreatic β cell apoptosis， insulin signal transduction， and other physiological functions. Therefore， blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present， Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections， but the adverse reactions are obvious. TCM has been characterized by multi-target， extensive action， and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation， regulating qi and eliminating phlegm， clearing heat and detoxifying， and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper， the association between NF-κB signaling pathway and diabetes was summarized， and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed， so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.

Child ; Humans ; Granulomatous Disease, Chronic/complications* ; Pneumonia

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To compare the accuracy of bedside lung ultrasound in emergency(BLUE)and combined cardiac-lung and additional ultrasound(CLAUS)for diagnosing the causes of acute dyspnea.Methods Totally 1 016 patients with acute dyspnea were retrospectively enrolled and divided into cardiogenic pulmonary edema group(n=268),pneumonia group(n=574),pneumothorax group(n=33),pulmonary embolism group(n=67)and CAD(chronic obstructive pulmonary disease/asthma/diaphragmatic dysfunction)group(n=74)according to the causes of acute dyspnea.The findings of CLAUS protocol were compared among groups,and the accuracy of BLUE and CLAUS protocol for diagnosing the causes of acute dyspnea were also compared.Results CLAUS showed that B-B and B-C were the most common modes in cardiogenic pulmonary edema group,while A-B/A-C/B-A/B-B/B-C/C-C modes were common in pneumonia group,and A-A mode was the most common in pneumothorax group,pulmonary embolism group and CAD group.Significant differences of the manifestations of pulmonary ultrasound,pleural feature of anterior chest wall,left/right cardiac insufficiency and abnormal inferior vena cava diameter were found among groups(all P＜0.05).The accuracy of BLUE and CLAUS protocol for diagnosing the causes of acute dyspnea was 86.91%(883/1 016)and 94.49%(960/1 016),respectively,the latter was higher than the former(χ2=34.587,P＜0.05).Conclusion CLAUS protocol could be used to effectively diagnose the causes of acute dyspnea,with higher accuracy than BLUE protocol.