1.AI-integrated IQPD framework of quality prediction and diagnostics in small-sample multi-unit pharmaceutical manufacturing: Advancing from experience-driven to data-driven manufacturing.
Kaiyi WANG ; Xinhai CHEN ; Nan LI ; Huimin FENG ; Xiaoyi LIU ; Yifei WANG ; Yanfei WU ; Yufeng GUO ; Shuoshuo XU ; Lu YAO ; Zhaohua ZHANG ; Jun JIA ; Zhishu TANG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2025;15(8):4193-4209
The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.
2.Xanthones from Garcinia pedunculata and Garcinia nujiangensis and their anti-inflammatory activity.
Xiaojie FAN ; Yufeng JIA ; Jiaxin GUO ; Jinyuan YANG ; Dahong LI ; Huiming HUA
Chinese Journal of Natural Medicines (English Ed.) 2025;23(2):225-233
Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC50 values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use*
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Garcinia
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Anti-Inflammatory Agents/therapeutic use*
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Plant Preparations/therapeutic use*
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Structure-Activity Relationship
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Nitric Oxide/metabolism*
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RAW 264.7 Cells
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Animals
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Mice
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Enzyme-Linked Immunosorbent Assay
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Mitogen-Activated Protein Kinase Kinases/metabolism*
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Circular Dichroism
3.Oxidative Stress-related Signaling Pathways in Lung Cancer and Chinese Medicine Intervention: A Review
Anqi LYU ; Yufeng SHI ; Cheng JIANG ; Jia KE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):228-237
Lung cancer has the highest incidence and mortality rate among all cancers in China, with its complex and variable nature, long treatment duration, and often poor prognosis. Currently, the treatment of lung cancer mainly employs classical therapies such as surgery, radiotherapy, and chemotherapy, but some patients may experience a series of adverse reactions, which affect their quality of life, survival period, and treatment outcomes. As reported, oxidative stress is one of the important pathogenic factors of lung cancer, affecting its occurrence and development. Oxidative stress is a state of imbalance between oxidative products and antioxidant defense mechanisms in the body. The intervention of oxidative stress in the occurrence and development of lung cancer is related to multiple signaling pathways, including the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and nuclear factor-κB (NF-κB) signaling pathway. Currently, researchers in China and abroad have conducted extensive studies on the occurrence and development of lung cancer and the pathophysiological mechanisms of drug intervention. The results have shown that oxidative stress plays an important role in the occurrence and development of lung cancer. Chinese medicine monomers and compounds can regulate oxidative stress levels and intervene in related signaling pathways, thereby inhibiting or delaying the occurrence and development of lung cancer. Based on this, this article mainly summarized the relevant signaling pathways regulating oxidative stress intervention in lung cancer in recent years, and also reviewed the latest research on Chinese medicine monomers and compounds in regulating oxidative stress to treat lung cancer, aiming to provide new ideas for research on drug treatment of lung cancer and clinical drug development, as well as to provide references and guidance for further in-depth mechanistic studies in the future.
4.Ginsenosides in Treatment of Lung Cancer: A Review
Anqi LYU ; Yufeng SHI ; Jia KE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):270-280
Lung cancer is the leading cause of cancer-related death, characterized by high invasiveness, early metastasis and poor prognosis. It has the highest incidence and mortality rates among cancers in China. Currently, the treatment of lung cancer is still dominated by the classic therapies such as surgery, radiotherapy, chemotherapy and targeted therapy. However, the classic therapies are not suitable for all patients with lung cancer, so new treatment strategies and methods are needed to prevent and treat lung cancer. In recent years, Ginseng Radix et Rhizoma has attracted wide attention in the field of anti-lung cancer research, and traditional Chinese medicine has a substantial theoretical and practical foundation in treating lung cancer. Ginseng Radix et Rhizoma , as a commonly used Chinese herbal medicine, has the functions of replenishing vital Qi, replenishing veins, strengthening the spleen and lung, and nourishing body and blood. The main active components of Ginseng Radix et Rhizoma , known as ginsenosides, exhibit anti-cancer and anti-inflammatory activities. Therefore, the mechanism and pharmacological activity of ginsenosides in the intervention of lung cancer have been extensively studied by researchers worldwide. The results show that ginsenosides can effectively inhibit the proliferation, invasion, migration, epithelial-mesenchymal transition and angiogenesis of lung cancer cells. Additionally, they inhibit drug resistance, enhance chemotherapy sensitivity and efficacy, and promote apoptosis and autophagy of lung cancer cells. Ginsenosides also modulate the tumor microenvironment and regulate immunity, thereby delaying the occurrence and development of lung cancer. The rapid advancements in related research have outpaced previous literature review, creating challenges for scholars seeking the latest information. Based on this, this article summarizes recent findings on the mechanism and pharmacological activities of ginsenosides in lung cancer intervention, aiming to provide new insights for the development of molecular biology, drug treatment research and clinical new drug research in lung cancer. It also provides the reference for further mechanism research.
5.Efficacy of tele-rehabilitation program for preschool children with functional articulation disorders
Yufeng JIA ; Yang LI ; Shuang ZHANG ; Shuzhi GAO ; Jingyun GAO ; Shuang LI
Chinese Journal of Child Health Care 2024;32(2):223-227
【Objective】 To observe the effect of tele-rehabilitation program on the articulation resolution of preschool children with functional articulation disorders (FAD), so as to provide reference for the clinical application of tele-rehabilitation in this context. 【Methods】 A total of 66 preschool children diagnosed with FAD in the outpatient department of Child Rehabilitation, Tangshan Maternal and Child Health Hospital from March 2022 to March 2023 were selected into this study, and were divided into tele-rehabilitation group (n=32) and control group (n=34) by random number table method. The control group received daily family rehabilitation guidance, while the tele-rehabilitation group underwent a tele-rehabilitation program lasting for 3 months. All children were assessed using the Chinese phonological ability evaluation lexicon before and 3 months after the treatment. 【Results】 After 3 months of treatment, both the tele-rehabilitation group and the control group showed significant improvements in articulation resolution compared to before treatment (t=12.165、12.986, P<0.05). Notably, the tele-rehabilitation group exhibited significantly greater improvement than the control group (t=2.138, P<0.05). Within the tele-rehabilitation group, children were further divided into three subgroups based on the severity of their dysphonia: mild, moderate, and severe. After 3 months of treatment, the articulation resolution of the mild and moderate groups improved significantly compared to before treatment (Z=2.226, 31.900, P<0.05), whereas no statistically significant improvement was observed in the severe group compared to before treatment (Z=1.857, P>0.05). 【Conclusion】 Tele-rehabilitation program effectively improves articulation resolution in preschool children with FAD, especially for mild to moderate preschool children with FAD.
6.TU Jinwen's Experience in the Treatment of Severe Influenza Based on the “Heat Toxin Theory”
Anqi LYU ; Yufeng SHI ; Yi YANG ; Jia KE ; Jinwen TU
Journal of Traditional Chinese Medicine 2024;65(7):674-677
To summarize Professor TU Jinwen's clinical experience in the treatment of severe influenza based on the “heat toxin theory”. He believed that “heat toxin” is the main disease mechanism of severe influenza, emphasized the pathogenesis process that toxin enters with the pathogenic qi, heat generates by the toxin, and changes initiate from the toxin, and proposed simultaneous treatment of warmth and toxin and combination of multiple methods as the treatment principles. Syndrome differentiation in clinic should combine with wei-qi-ying-blood. The disease in the early stage located in wei (defensive) and qi level, treated by clearing heat and resolving toxins, releasing the exterior and expelling pathogen, harmonizing the exterior and interior, dredging the bowels with diarrhea, and combining other methods to get rid of the heat and toxin, and modified Self-Prescribed Tuire No. 1 Formula (自拟退热1号方) is recommended; the disease in progression stage located in ying-blood, treated by relieving heat and resolving toxins, and clearing the ying level and cool the blood, with prescriptions as modified Self-Prescribed Tuire No. 1 Formula plus Qingying Decoction (清营汤), or Xijiao Dihuang Decoction (犀角地黄汤); the disease in the late stage with of yin fluid consumption, and heat toxin in the blood level, treated by eliminating heat and resolving toxins, and enriching yin and cooling the blood, with prescriptions as modified Shashen Maidong Decoction (沙参麦冬汤) and Zhuye Shigao Decoction (竹叶石膏汤). At the same time, it is emphasised that heat-clearing and fire-draining method and harmonising methods are important, and that dispelling pathogen should not injure healthy qi, and that the selection of prescriptions and medicines need consider syndrome differentiation and treatment.
7.REDH: A database of RNA editome in hematopoietic differentiation and malignancy
Jiayue XU ; Jiahuan HE ; Jiabin YANG ; Fengjiao WANG ; Yue HUO ; Yuehong GUO ; Yanmin SI ; Yufeng GAO ; Fang WANG ; Hui CHENG ; Tao CHENG ; Jia YU ; Xiaoshuang WANG ; Yanni MA
Chinese Medical Journal 2024;137(3):283-293
Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.
8.Correlation between variability of blood uric acid level and progression of type 2 diabetic nephropathy and retinopathy
Nan JIA ; Lijuan WANG ; Zuodi FU ; Lianying WANG ; Yufeng LI
Chinese Journal of Postgraduates of Medicine 2024;47(5):450-455
Objective:To investigate the correlation between the variability of blood uric acid level and the progression of type 2 diabetic nephropathy and retinopathy.Methods:A total of 240 patients with type 2 diabetic nephropathy were selected from a cohort established in Pinggu District Hospital of Beijing in 2015 for retrospective analysis. The blood uric acid level of the patients was measured, the variability of uric acid level was calculated, and the patients were divided into group A, group B, group C and group D according to the quartile of uric acid variability, with 60 cases in each group. The subjects were followed up, and their general information, biochemical indicators, diabetic nephropathy and diabetic retinopathy were collected. According to the diabetic nephropathy and retinopathy during follow-up, the subjects were divided into progressive group and non-progressive group, so as to further clarify the correlation between the variability of blood uric acid level and the progression of diabetic nephropathy and retinopathy.Results:Up to the last follow-up date in July 2022, a total of 24 cases were lost to follow-up in group A, 27 cases in group B, 20 cases in group C, and 22 cases in group D. Finally, 36 cases were included in group A, 33 cases in group B, 40 cases in group C, and 38 cases in group D. There was no significant difference in age, gender, body mass index, systolic blood pressure, diastolic blood pressure, cholesterol, triglyceride, low density lipoprotein cholesterol, fasting blood glucose, glycated hemoglobin and serum creatinine among four groups ( P>0.05). Univariate analysis showed that the incidence of diabetic nephropathy and retinopathy progression increased with the increase of the quartile of uric acid variability in patients with type 2 diabetes (the incidences of progression in A, B, C and D groups were 16%, 49%, 63% and 79%, F = 0.95, P<0.05). Pearson correlation analysis showed that blood uric acid variability was positively correlated with the progression of diabetic nephropathy and retinopathy ( r = 0.482 and 0.501, P<0.05). Logistics regression analysis showed that with the increase of the quartile of uric acid variability, the progression risk of diabetic nephropathy ( OR = 3.521, 5.226 and 6.548; P<0.05) and retinopathy ( OR = 3.733, 4.844 and 5.872; P<0.05) in type 2 diabetes patients increased gradually. Conclusions:The variability of blood uric acid level is positively correlated with the progression of type 2 diabetic nephropathy and retinopathy. The higher the risk of progression of diabetic nephropathy and retinopathy with the increase of quartile of blood uric acid level variability, the more important it is to regularly monitor the blood uric acid level of type 2 diabetic patients.
9.Comparison of Jinzhen oral liquid and ambroxol hydrochloride and clenbuterol hydrochloride oral solution in the treatment of acute bronchitis in children: A multicenter, non-inferiority, prospective, randomized controlled trial.
Qinhua FAN ; Chongming WU ; Yawei DU ; Boyang WANG ; Yanming XIE ; Zeling ZHANG ; Wenquan SU ; Zizhuo WANG ; Changchang XU ; Xueke LI ; Ying DING ; Xinjiang AN ; Jing CHEN ; Yunying XIAO ; Rong YU ; Nan LI ; Juan WANG ; Yiqun TENG ; Hongfen LV ; Nian YANG ; Yuling WEN ; Xiaoli HUANG ; Wei PAN ; Yufeng LIU ; Xueqin XI ; Qianye ZHAO ; Changshan LIU ; Jian XU ; Haitao ZHANG ; Lie ZHUO ; Qiangquan RONG ; Yu XIA ; Qin SHEN ; Shao LI ; Junhong WANG ; Shengxian WU
Acta Pharmaceutica Sinica B 2024;14(12):5186-5200
The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.
10.Localization of epileptic foci in intractable epilepsy induced by hippocampal sclerosis by 11C-choline PET/CT dynamic brain imaging
Lingling LU ; Yufeng CHEN ; Jia GUO ; Guoxu ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(1):12-16
Objective:To evaluate the diagnostic value of 11C-choline PET/CT brain imaging for localization of epileptogenic foci in hippocampal sclerosis-refractory temporal lobe epilepsy (HS-RTLE), and compare it with 18F-FDG and 11C-flumazeni (FMZ) PET/CT. Methods:From March 2017 and June 2020, a total of 62 patients (39 males, 23 females, age (30.3±11.2) years) with pathologically confirmed HS-RTLE in General Hospital of Northern Theater Command were retrospectively analyzed. All patients were preoperatively treated with multiple radionuclide ( 18F-FDG, 11C-FMZ, 11C-choline) PET/CT brain imaging. 11C-choline PET imaging was used to acquire dynamic imaging data and time-activity curve (TAC) of 11C-choline in bilateral hippocampal regions were drawn. With postoperative pathology as the " gold standard" , the positive detection rates and localization diagnostic efficacies of three radionuclide imaging agents for epileptogenic foci were analyzed. Then a prospective study including 46 patients (27 males, 19 females; age (32.9±11.9) years; between May 2019 and August 2020; General Hospital of Northern Theater Command) with drug-refractory epilepsy caused by clinically suspected hippocampal sclerosis was performed. The examination method was the same as that of retrospective study. Using intracranial electrode implantation or postoperative pathology as " gold standard" , the diagnostic efficacy of 11C-choline TAC for localization of epileptogenic foci was verified, and ROC curve was drawn to evaluate the diagnostic value of three imaging agents for HS-RTLE epileptogenic foci. χ 2 test and Fisher exact probability method, Delong test were used to analyze the data. Results:In the retrospective study, the positive detection rate of 18F-FDG PET/CT was higher than that of 11C-choline PET/CT (100%(62/62) vs 85.48%(53/62); P=0.003), and the localization accuracies of 11C-choline and 11C-FMZ PET/CT were both higher than that of 18F-FDG PET/CT (100%(53/53), 96.61%(57/59) vs 33.87%(21/62); both P<0.001). In the prospective study, 25 of 46 patients were diagnosed as HS-RTLE and 21 were non-HS induced epilepsy. The specificities of 11C-choline, 11C-FMZ and 18F-FDG PET/CT were 100%(21/21), 90.48%(19/21), 33.33%(7/21), respectively. The AUCs of 11C-choline and 11C-FMZ PET/CT were significantly higher than that of 18F-FDG PET/CT (0.920, 0.912, 0.627; z values: 4.93, 5.16, both P<0.01). Conclusions:11C-choline PET/CT can be used in the preoperative localization of epileptic foci. Compared with 18F-FDG and 11C-FMZ PET/CT, the specificity of 11C-choline PET/CT is higher, and the negative imaging of 11C-choline is more significant for exclusion.

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