1.Exploration of Pulmonary Vascular Remodeling Improvement in Rats at Different Stages of Chronic Obstructive Pulmonary Disease by Qibai Pingfei Capsules Based on TLR4/NF-κB Signaling Pathway
Lu ZHANG ; Li FANG ; Shuyu XU ; Xue LIANG ; Jie ZHU ; Xiangli TONG ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):48-56
ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease (COPD) and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley (SD) rats were randomly divided into a normal group, an early COPD model group, an advanced COPD model group, an early-intervention high-dose group, a late-intervention high-dose group, an early-intervention low-dose group, a late-intervention low-dose group, an early-intervention pyrrolidine dithiocarbamate (PDTC) group, and a late-intervention PDTC group, with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide(LPS), and a rat model of advanced COPD was constructed by using airway infusion with LPS, cigarette smoke, and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment, smoked for 1 h per day, and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups, rats were given 1 g·kg-1 and 250 mg·kg-1 Qibai Pingfei capsules, respectively by gavage, and in PDTC groups, rats were given 100 mg·kg-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin(HE)staining. Collagen deposition in lung tissues was examined by Masson staining, and the levels of inflammatory factors including interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA). The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining, and the protein expression of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-κB(NF-κB), TNF-α, vascular endothelial-cadherin(VE-cadherin), α-smooth muscle actin(α-SMA), and platelet endothelial cell adhesion molecule-1(CD31) was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group, the model group showed significantly decreased forced expiratory volume in 0.3 s (FEV0.3), forced vital capacity (FVC), and FEV0.3/FVC ratio related to lung function (P<0.05), thickening of pulmonary vasculature, increased collagen deposition in the lungs, and enhanced mean pulmonary arterial pressure and expression levels of IL-6, IL-1β, and TNF-α (P<0.05). Additionally, the model group also exhibited increased numbers of macrophages, lymphocytes, and neutrophils (P<0.05), significantly higher protein expression of TLR4, MyD88, NF-κB, TNF-α, and α-SMA (P<0.05), and significantly lower protein expression of VE-cadherin and CD31 (P<0.05). Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group (P<0.05), with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6, IL-1β, and TNF-α (P<0.05) and decreased numbers of macrophages, lymphocytes, and neutrophils (P<0.05), as well as reduced protein expression of TLR4, MyD88, NF-κB, TNF-α, and α-SMA (P<0.05) and elevated protein expression of VE-cadherin and CD31 (P<0.05) in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway, thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.
2.Multidimensional optimization strategies and practical effects of prescription pre-review system
Guangming GAO ; Tianjiao LIU ; Na XU ; Jing LIANG ; Xiangju SUN ; Zhanguo ZHU ; Hong YAN
China Pharmacy 2025;36(14):1797-1801
OBJECTIVE To optimize the prescription pre-review system in our hospital and evaluate its application effects. METHODS Aiming at the problems of imperfect rule base and high false positive rate in the early operation of the system, optimization measures were taken, including improving the content of the rule base, adjusting the interception level and prompt mode, refining the working model of prescription review pharmacists, and strengthening clinical communication. A retrospective cohort study was conducted, with prescription data from June to December 2023 (before optimization) as the control group and June to December 2024 (after optimization) as the observation group. Through inter group comparative analysis, the actual effect of optimizing the prescription pre-approval system was evaluated. RESULTS The prescription qualified rate increased from (82.51± 4.04)% before optimization to (90.98±1.55)% after optimization; the false positive rate decreased from (20.87±1.64)% before optimization to (7.41±2.04)% after optimization. The monthly range of prescription qualified rate narrowed from 10.24% to 4.11%, and the coefficient of variation decreased from 4.92% to 1.73%. The monthly range of false positive rate slightly increased from 4.40% to 5.34%, the coefficient of variation rose from 8.32% to 26.18%. CONCLUSIONS Through multi-dimensional optimizations of the prescription pre-review system in our hospital, its prescription review efficiency has been significantly enhanced, the quality of prescriptions has steadily improved, and the accuracy of reviews has notably improved.
3.Construction and application of the criteria for drug utilization evaluation of low-dose rivaroxaban in atherosclerotic cardiovascular disease
Liang WU ; Wei WANG ; Yanghui XU ; Bo ZHU ; Yijun KE
China Pharmacy 2025;36(17):2176-2181
OBJECTIVE To construct and apply drug utilization evaluation (DUE) criteria for low-dose rivaroxaban in atherosclerotic cardiovascular disease (ASCVD) based on the dual pathway inhibition (DPI) antithrombotic therapy scheme, to promote clinical rational drug use. METHODS Based on the instructions and relevant guidelines of low-dose rivaroxaban (2.5 mg, bid), the Delphi method was used to establish the DUE criteria for low-dose rivaroxaban used in ASCVD. Weighted technique for order preference by similarity to an ideal solution method was used to determine the relative weights of each evaluation index, and the rationality of the filing medical records of discharged patients using low-dose rivaroxaban for ASCVD at Anqing Municipal Hospital from February 2024 to January 2025 was evaluated. RESULTS The established DUE criteria included 3 primary indicators (medication indications, medication process, medication results) and 11 secondary indicators (such as indications, contraindications, etc.). The higher weighted secondary indicators being contraindications (0.117 9) and indications (0.112 1). A total of 265 medical records were included for evaluation. The evaluation results showed that 192 cases (72.45%) had reasonable medical records, 69 cases (26.04%) had basic reasonable medical records, and 4 cases (1.51%) had unreasonable medical records; unreasonable types mainly included inappropriate combination therapy, inappropriate usage and dosage, inappropriate post- medication monitoring, and inappropriate drug switching, etc. CONCLUSIONS This study establishes a DUE criteria for low-dose rivaroxaban in ASCVD based on the DPI antithrombotic treatment regimen, and the evaluation results are intuitive, reliable, and quantifiable. The use of low-dose rivaroxaban in ASCVD patients in our hospital is relatively reasonable, but further management needs to be strengthened.
4.Two new dalbergiphenols from Zhuang medicine Dalbergia rimosa Roxb
Cheng-sheng LU ; Wei-yu WANG ; Min ZHU ; Si-si QIN ; Zhao-hui LI ; Chen-yan LIANG ; Xu FENG ; Jian-hua WEI
Acta Pharmaceutica Sinica 2024;59(2):418-423
Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of
5.Value of Head and Neck 4D-CTA Combined with SDF-1a/CXCR4 Signaling Pathway in Assessing the Risk of Ruptured Intracranial Posterior Communicating Aneurysms
Yiming XU ; Jianfeng ZHONG ; Bin LI ; Xinyan ZHOU ; Hongli ZHU ; Jing LIANG ; Chengde LIAO
Journal of Kunming Medical University 2024;45(3):59-64
Objective To investigate the value of 4D-CTA combined with SDF-1a/CXCR4 signaling pathway in evaluating the risk of intracranial aneurysm rupture.Methods Fifty patients with unruptured intracranial posterior communicating aneurysms and 50 patients with ruptured intracranial posterior communicating aneurysms were divided into unruptured group 1 and ruptured group 1.All patients underwent 4D-CTA examination and serumSDF-1alevel was detected.Non-ruptured group 1 was followed up for 12 months(After conservative treatment),on this basis,patients with ruptured posterior communicating aneurysms were included in ruptured group 2,and patients with unruptured posterior communicating aneurysms were included in non-ruptured group 2.Results The AUC values of Wn,AR,L,SR,SDF-1a and their combinations in diagnosing ruptured intracranial posterior communicating aneurysms were all greater than 0.70.The AUC values of Wn,AR,L,SR,SDF-1a and their combinations in predicting ruptured intracranial posterior communicating aneurysms in ruptured group 2 were all greater than 0.70.Conclusion 4D-CTA combined with SDF-1acan effectively distinguish ruptured intracranial posterior communicating aneurysms and predict the risk of rupture.
6.Correlation between the expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1beta in nucleus pulposus and the degree of lumbar intervertebral disc degeneration
Shuliang ZHOU ; Liang XU ; Xuefeng QIAN ; Jincai ZENG ; Lifan ZHU
Chinese Journal of Tissue Engineering Research 2024;28(2):165-171
BACKGROUND:MicroRNA(miRNA)levels are closely related to cell apoptosis and proliferation,extracellular matrix metabolism and inflammatory response in intervertebral disc cells.However,the specific role of miR-142-3p in lumbar intervertebral disc degeneration remains unclear. OBJECTIVE:To investigate the correlation between the expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1β in nucleus pulposus tissue and degree of human lumbar intervertebral disc degeneration. METHODS:A total of 82 patients with lumbar intervertebral disc degenerative diseases in Suzhou Ninth People's Hospital from January 2020 to March 2022 were collected as the study subjects,all of whom underwent MRI examination before operation.According to the Videman classification,the patients were divided into mild degeneration group(n=36),moderate degeneration group(n=26)and severe degeneration group(n=20).Eighty-two specimens of the nucleus pulposus were obtained.The mRNA expression of miRNA-142-3p as well as the mRNA and protein expression of mixed lineage kinase 3,interleukin-1β,type I collagen,type II collagen in nucleus pulposus tissue were detected by qPCR and western blot assay.The correlation between the degree of human lumbar intervertebral disc degeneration and the expression levels of miRNA-142-3p,mixed lineage kinase 3,and interleukin-1β was also assessed using the Spearman correlation coefficient method.Thirty adult Sprague-Dawley rats were divided into sham-operated group(executed after puncturing skin and muscle only),mild degeneration group(executed 1 week after puncturing Co7/8 segments)and severe degeneration group(executed 2 weeks after puncturing Co7/8 segments),with 10 rats in each group.After that,we detected the protein expression of mixed lineage kinase 3 and interleukin-1β as well as the gene expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1β in the nucleus pulposus tissue. RESULTS AND CONCLUSION:In human nucleus pulposus tissue,the miRNA-142-3p expression ranked from high to low as follows:mild degeneration group>moderate degeneration group>severe degeneration group(P<0.05);the gene and protein expression of mixed lineage kinase 3 and interleukin-1β from low to high was as follows:mild degeneration group
7.Establishment and validation of a predictive model for the progression of pancreatic cystic lesions based on clinical and CT radiological features
Wenyi DENG ; Feiyang XIE ; Li MAO ; Xiuli LI ; Zhaoyong SUN ; Kai XU ; Liang ZHU ; Zhengyu JIN ; Xiao LI ; Huadan XUE
Chinese Journal of Pancreatology 2024;24(1):23-28
Objective:To construct a machine-learning model for predicting the progression of pancreatic cystic lesions (PCLs) based on clinical and CT features, and to evaluate its predictive performance in internal/external testing cohorts.Methods:Baseline clinical and radiological data of 200 PCLs in 177 patients undergoing abdominal thin slice enhanced CT examination at Peking Union Medical College Hospital from July 2014 to December 2022 were retrospectively collected. PCLs were divided into progressive and non-progressive groups according to whether the signs indicated for surgery by the guidelines of the European study group on PCLs were present during three-year follow-up. 200 PCLs were randomly divided into training (150 PCLs) and internal testing cohorts (50 PCLs) at the ratio of 1∶3. 15 PCLs in 14 patients at Jinling Affiliated Hospital of Medical School of Nanjing University from October 2011 to May 2020 were enrolled as external testing cohort. The clinical and CT radiological features were recorded. Multiple feature selection methods and machine-learning models were implemented and combined to identify the optimal machine-learning model based on the 10-fold cross-validation method. Receiver operating characteristics (ROC) curve was drawn and area under curve (AUC) was calculated. The model with the highest AUC was determined as the optimal model. The optimal model's predictive performance was evaluated on testing cohort by calculating AUC, sensitivity, specificity and accuracy. Permutation importance was used to assess the importance of optimal model features. Calibration curves of the optimal model were established to evaluate the model's clinical applicability by Hosmer-Lemeshow test.Results:In training and internal testing cohorts, the progressive and non-progressive groups were significantly different on history of pancreatitis, lesions size, main pancreatic duct diameter and dilation, thick cyst wall, presence of septation and thick septation (all P value <0.05) In internal testing cohort, the two groups were significantly different on gender, lesion calcification and pancreatic atrophy (all P value <0.05). In external testing cohort, the two groups were significantly different on lesions size and pancreatic duct dilation (both P<0.05). The support vector machine (SVM) model based on five features selected by F test (lesion size, thick cyst wall, history of pancreatitis, main pancreatic duct diameter and dilation) achieved the highest AUC of 0.899 during cross-validation. SVM model for predicting the progression of PCLs demonstrated an AUC of 0.909, sensitivity of 82.4%, specificity of 72.7%, and accuracy of 76.0% in the internal testing cohort, and 0.944, 100%, 77.8%, and 86.7% in the external testing cohort. Calibration curved showed that the predicted probability by the model was comparable to the real progression of PCLs. Hosmer-Lemeshow goodness-of-fit test affirmed the model's consistency with actual PCLs progression in testing cohorts. Conclusions:The SVM model based on clinical and CT features can help doctors predict the PCLs progression within three-year follow-up, thus achieving efficient patient management and rational allocation of medical resource.
8.Clinical characteristics analysis of primary pancreatic lymphoma
Yinghao SUN ; Jianing LI ; Kun HE ; Liang ZHU ; Yunlu FENG ; Qiang WANG ; Qingwei JIANG ; Yan ZHANG ; Qiang XU ; Zheng WANG ; Jingya ZHOU ; Dong WU
Chinese Journal of Pancreatology 2024;24(1):52-56
Objective:To analyze clinical characteristics of primary pancreatic lymphoma (PPL) patients.Methods:Clinical features of 22 patients diagnosed as PPL admitted to Peking Union Medical College Hospital from January 2002 to May 2023 were analyzed retrospectively.Results:The median age was 56.4±13.3 years. The median time from onset to diagnosis was 1.0 (1.0, 3.0) months. The main clinical manifestations were abdominal pain (15/22), weight loss (14/22) and jaundice (10/22). Elevated lactate dehydrogenase (LDH) was observed in 15/20 (75%) patients. Only 2 (2/9, 22.2%) patients had increased CA199 levels and 2 (2/9, 22.2%) patients had increased CEA levels. The maximum tumor diameter was 5.0 (3.8, 6.9) cm. Contrast-enhanced CT mostly showed low enhancement lesions. Major pancreatic duct dilatation were rare on CT scan (4/20). Fifteen patients were confirmed by pancreatic pathology, of which 8 were obtained by surgery, 4 were obtained by CT or ultrasound-guided percutaneous biopsy, and 3 were obtained by EUS-FNA. The main pathological type was diffuse large B-cell lymphoma (14/22). 19 patients received chemotherapy, and 6 patients died with a median follow-up of 5.0 (1.5, 35.5) months.Conclusions:PPL is rare and easy to be misdiagnosed. Elevated LDH levels, normal tumor markers, and non-dilatation of main pancreatic duct are important diagnostic clues. It is important to obtain pathology by EUS-FNA and other methods for definite diagnosis.
9.Application of two different methods of visual acuity assessment for myopia screening among lower grade elementary school students
LIANG Li, XU Shaojun, ZHU Yi, XU Xing, ZHAO Mengya, WEN Yuechun, TAO Fangbiao
Chinese Journal of School Health 2024;45(2):273-276
Objective:
To explore two visual acuity standards for examining uncorrected visual acuity (UCVA) to define poor vision in lower grade elementary school students, and to compare the difference of screening myopia rates when combined with non cycloplegic auto refraction (NCAR), so as to provide a scientific basis for standardizing UCVA examination methods using CAR as the gold standard of authenticity and reliability.
Methods:
From March 22nd to April 9th, 2023, a total of 549 first and second grade students aged 7-8 years from a primary school in Hefei City were selected for the study by convenient cluster sampling method. Two methods were employed for UCVA examination:the first method involved charts where the student could not make mistakes in identifying at least half of the characters per line (V1), and the second method used charts with character sizes ranging from 4.0 -4.5, 4.6-5.0 and 5.1-5.3, without allowing 1, 2 and 3 errors per line (V2). While NCAR was performed, then 187 students underwent CAR examination. Paired Wilcoxon rank-sum test and McNemar test were used to compare the differences between V1 and V2 methods in defining poor vision and screening myopia rates. Using CAR as the gold standard, the authenticity and reliability of defining screening myopia rates through the combination of V1 and V2 methods along with NCAR were evaluated.
Results:
The UCVA examination results for V1 and V2 showed statistically significant differences in both the right eye [5.0(4.9,5.0), 4.9(4.8,5.0)] and the left eye [ 5.0 (4.9,5.0), 4.9(4.8,5.0)] ( Z=-13.95, -13.34, P <0.01). The detection rates of poor vision for the right eye were 43.53% for V1 and 63.21% for V2, and the left eye with 44.08% for V1 and 62.11% for V2, with statistically significant differences ( χ 2= 106.01 , 95.09, P <0.01). When screening myopia rates were assessed for UCNA methods combined with NCAR, the right eye rates were 21.49% for V1 and 24.59% for V2, and the left eye rates were 21.31% for V1 and 23.13% for V2, with statistically significant differences ( χ 2=15.06, 8.10, P <0.01). Using CAR as the gold standard, the detection rates in the right eye and left eye were 16.58 % and 17.11%, respectively. The Youden indices for defining screening myopia in the right eye were 0.80 for V1 and 0.79 for V2, and the left eye with 0.85 for V1 and 0.83 for V2. The agreement rates for the right eye were 91.98 % for V1 and 89.30% for V2, and the left eye with 94.12% for V1 and 91.98% for V2. The Kappa values for the right eye were 0.73 for V1 and 0.67 for V2, and the left eye with 0.81 for V1 and 0.75 for V2.
Conclusions
Authenticity and reliability of two UCVA examination methods combined with NCAR in defining screening myopia are higher in V1 than V2 methods. It is recommended to unify the visual acuity examination methods by requiring the correct identification of more than half of the total number of visual markers in a row.
10.Exploring the Mechanism of Action of Qizhu Kang'ai Formula (芪术抗癌方) for the Treatment of Colorectal Cancer based on Network Pharmacology and Experimental Validation
Ruolan SUN ; Yan LIANG ; Fan ZHAO ; Shijiao ZHU ; Linlu WAN ; Xu WANG ; Qihang YIN ; Gang YIN ; Decai TANG
Journal of Traditional Chinese Medicine 2024;65(4):404-413
ObjectiveTo explore the potential molecular mechanism of Qizhu Kang'ai Formula (芪术抗癌方, QZKAF) for the treatment of colorectal cancer (CRC). MethodsNetwork pharmacology was used to analyze the active ingredients and targets of QZKAF for CRC, and analyze the key targets of QZKAF for the treatment of CRC by gene function annotation (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment analysis. Molecular docking was applied to predict the binding activity of the core active ingredients to the key targets. A orthotopic transplantation tumor mice model of CRC was established to validate the key targets of QZKAF for CRC obtained from network pharmacology analysis. Forty-eight mice were randomly divided into the sham operation group, the model group, the 5-fluorouracil (5-Fu) group, and the QZKAF low-, medium-, and high-dose groups, with 8 mice in each group. Except for the sham operation group, the remaining groups underwent colon cancer orthotopic transplantation tumor modeling. The 5-Fu group was given 30 mg/kg of 5-Fu by intraperitoneal injection once every 3 days on the alternate day after modeling, while the QZKAF low-, medium-, and high-dose groups were given 2.925, 5.85, and 11.7 g/(kg·d) of QZKAF by gastric gavage, respectively, and the sham-operation group and the model group were gavaged with 0.1 ml/10 g of normal saline every day, all for 21 days. The in situ tumors mass and the number of liver metastases were compared between the groups. The pathological changes of colon tumor tissues were observed by HE staining, and the protein expression of protein tyrosine phosphatase nonreceptor type 1 (PTPN1), vinculin, integrin subunit αν, integrin subunit β3, and E-cadherin were detected in colon tumor tissues by Western blot. ResultsNetwork pharmacology screening yielded that the top six core active ingredients of QZKAF intervening in CRC were quercetin, kaempferol, apigenin, luteolin, baicalein and ursolic acid. There were 212 targets of action, and the ranked top three were prostaglandin endoperoxide synthase 1 (PTGS1), prostaglandin endoperoxide synthase 2 (PTGS2), and PTPN1, which may be the key targets of QZKAF in the treatment of CRC. These key targets were significantly enriched mainly in phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt) signaling pathway, focal adhesion and adhesion junction. Molecular docking results: except for PTGS1 with better binding activity to quercetin, kaempferol, and apigenin (binding energy ≥


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