1.Enzyme-directed Immobilization Strategies for Biosensor Applications
Xing-Bao WANG ; Yao-Hong MA ; Yun-Long XUE ; Xiao-Zhen HUANG ; Yue SHAO ; Yi YU ; Bing-Lian WANG ; Qing-Ai LIU ; Li-He ZHANG ; Wei-Li GONG
Progress in Biochemistry and Biophysics 2025;52(2):374-394
Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.
2.Coral calcium hydride promotes peripheral mitochondrial division and reduces AT-II cells damage in ARDS via activation of the Trx2/Myo19/Drp1 pathway.
Qian LI ; Yang ANG ; Qing-Qing ZHOU ; Min SHI ; Wei CHEN ; Yujie WANG ; Pan YU ; Bing WAN ; Wanyou YU ; Liping JIANG ; Yadan SHI ; Zhao LIN ; Shaozheng SONG ; Manlin DUAN ; Yun LONG ; Qi WANG ; Wentao LIU ; Hongguang BAO
Journal of Pharmaceutical Analysis 2025;15(3):101039-101039
Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.
4.Risk factors for comprehensive complication index after radical resection of colon cancer and establishment of its dynamic nomogram prediction model
Yi-Fan SHI ; Xiao-Ming SHEN ; Zeng-Hui YANG ; Li XIA ; Bing-Hua XU ; Chuan-Qing BAO
Medical Journal of Chinese People's Liberation Army 2024;49(4):416-425
Objective To investigate the independent risk factors of comprehensive complication index(CCI)≥26.2 after radical resection of colon cancer,and use these factors to establish and verify a dynamic web-based nomogram model.Methods The clinical data of colon cancer patients who underwent radical resection in the Affiliated Hospital of Jiangnan University from November 2020 to April 2022 were retrospectively collected,and divided into main cohort(November 2020 to October 2021,n=438)and validation cohort(November 2021 to April 2022,n=196).CCI scores of all patients were obtained based on CCI calculator(http://www.assessurgery.com).Univariate and multivariate logistic regression analysis were performed to identify the risk factors for CCI≥26.2,and a nomogram model was constructed.Receiver operator characteristic curve(ROC),C index and calibration curve were used to evaluate the differentiation and consistency of predictive nomogram model,and the decision curve analysis was conducted to assess the clinical benefits of the model.Internal validation of the model is performed in the validation cohort.Results A total of 438 patients were identified in present study,of which 63 cases(14.4%)had CCI≥26.2.Multivariate logistic regression analysis revealed that age≥60 years(OR=2.662,95%CI 1.341-5.285,P=0.005),low third lumbar spine skeletal muscle mass index(L3MI;OR=4.572,95%CI 2.435-8.583,P<0.001),NRS2002≥3(OR=4.281,95%CI 2.304-7.952,P<0.001),and preoperative bowel obstruction(OR=3.785,95%CI 1.971-7.268,P<0.001)were significant independent risk factors for postoperative CCI≥26.2.Based on these results,a static and web-based dynamic nomogram was established(https://jndxfsyywcwksyf.shinyapps.io/DynNomCCI/).The C-index and area under the curve(AUC)of the nomogram were 0.742 and 0.787,respectively.The calibration curve indicated a good consistency between the predicted probability and the actual probability.In the validation cohort,the nomogram also presented good discrimination(C-index=0.722,AUC=0.795)and predictive consistency.The decision curve analysis indicated the clinical benefit and application value of the nomogram prediction model.Conclusion This easy-to-use dynamic nomogram based on 4 independent risk factors can conveniently and reliably predict the probability of CCI≥26.2 after radical resection of colon cancer,which helps optimize the preoperative evaluation system,formulate precise individualized treatment strategies,and enhance recovery after surgery.
5.Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population.
Meng Fan LIU ; Rui Xia MA ; Xian Bao CAO ; Hua ZHANG ; Shui Hong ZHOU ; Wei Hong JIANG ; Yan JIANG ; Jing Wu SUN ; Qin Tai YANG ; Xue Zhong LI ; Ya Nan SUN ; Li SHI ; Min WANG ; Xi Cheng SONG ; Fu Quan CHEN ; Xiao Shu ZHANG ; Hong Quan WEI ; Shao Qing YU ; Dong Dong ZHU ; Luo BA ; Zhi Wei CAO ; Xu Ping XIAO ; Xin WEI ; Zhi Hong LIN ; Feng Hong CHEN ; Chun Guang SHAN ; Guang Ke WANG ; Jing YE ; Shen Hong QU ; Chang Qing ZHAO ; Zhen Lin WANG ; Hua Bin LI ; Feng LIU ; Xiao Bo CUI ; Sheng Nan YE ; Zheng LIU ; Yu XU ; Xiao CAI ; Wei HANG ; Ru Xin ZHANG ; Yu Lin ZHAO ; Guo Dong YU ; Guang Gang SHI ; Mei Ping LU ; Yang SHEN ; Yu Tong ZHAO ; Jia Hong PEI ; Shao Bing XIE ; Long Gang YU ; Ye Hai LIU ; Shao wei GU ; Yu Cheng YANG ; Lei CHENG ; Jian Feng LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(6):579-588
Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female
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Humans
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Adolescent
;
SARS-CoV-2
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Smell
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COVID-19/complications*
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Cross-Sectional Studies
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COVID-19 Vaccines
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Incidence
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Olfaction Disorders/etiology*
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Taste Disorders/etiology*
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Prognosis
6.Analysis of acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack based on complex network.
Tian-Cheng XU ; Meng-Qing DING ; Yun-Fan BAO ; Cheng XU ; Rui WANG ; Ruo-Yun YANG ; Han-Yu DENG ; You-Bing XIA
Chinese Acupuncture & Moxibustion 2022;42(1):104-108
Acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack was analyzed based on complex network, acupoint names and indications were extracted from the book, which provided ideas and methods for promoting the modernization of acupuncture and moxibustion by using complex network technology. A total of 112 acupoints in 201 acupuncture prescriptions were included, and the total frequency of acupoints was 880 times, forming 42 034 acupoint pairs. In terms of network indexes, compared with the complex network of comprehensive acupuncture books, such as Meridian and Acupoint Science, Zhenjiu Dacheng, Acupuncture A and B Meridians formed based on the same mathematical method, the complex network model for CHENG Dan-an's Note About Treatise on Cold-Attack shows more typical small world effect, which is characterized by higher network density (6.762) and shorter average path length (1.064). This phenomenon may be related to the tongue and pulse which added the link between acupoints. For the node indexes, the analysis of topological indexes such as Page Rank shows that acupoints represented by Dazhui (GV 14) has higher compatibility value in the treatment of exogenous diseases, which further demonstrates the clinical value of eigenvector centrality in guiding intelligent compatibility of points.
Acupuncture
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Acupuncture Points
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Acupuncture Therapy
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Meridians
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Moxibustion
7.Naringenin inhibits thoracic aortic aneurysm formation in mice with Marfan syndrome.
Zhi Qing LI ; Bing YU ; Ze Yu CAI ; Ying Bao WANG ; Xu ZHANG ; Biao ZHOU ; Xiao Hong FANG ; Fang YU ; Yi FU ; Jin Peng SUN ; Wei LI ; Wei KONG
Journal of Peking University(Health Sciences) 2022;54(5):896-906
OBJECTIVE:
To identify whether naringenin plays a protective role during thoracic aneurysm formation in Marfan syndrome.
METHODS:
To validate the effect of naringenin, Fbn1C1039G/+ mice, the mouse model of Marfan syndrome, were fed with naringenin, and the disease progress was evaluated. The molecular mechanism of naringenin was further investigated via in vitro studies, such as bioluminescence resonance energy transfer (BRET), atomic force microscope and radioligand receptor binding assay.
RESULTS:
Six-week-old Fbn1C1039G/+ mice were fed with naringenin for 20 weeks. Compared with the control group, naringenin significantly suppressed the aortic expansion [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.49±0.47) mm, n=18 vs. (1.87±0.19) mm, n=22, P < 0.05], the degradation of elastin, and the expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the ascending aorta of Fbn1C1039G/+ mice. Besides, treatment with naringenin for 6 weeks also attenuated the disease progress among the 20-week-old Fbn1C1039G/+ mice with established thoracic aortic aneurysms [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.24±0.23) mm, n=8 vs. (1.90±0.17) mm, n=8, P < 0.05]. To understand the underlying molecular mechanisms, we examined the effects of naringenin on angiotensin Ⅱ type 1 receptor (AT1) signaling and transforming growth factor-β (TGF-β) signaling respectively, which were the dominant signaling pathways contributing to aortopathy in Marfan syndrome as previously reported. The results showed that naringenin decreased angiotensin Ⅱ (Ang Ⅱ)-induced phosphorylation of protein kinase C (PKC) and extracellular regulating kinase 1/2 (ERK1/2) in HEK293A cell overexpressing AT1 receptor. Moreover, naringenin inhibited Ang Ⅱ-induced calcium mobilization and uclear factor of activated T-cells (NFAT) signaling. The internalization of AT1 receptor and its binding to β-arrestin-2 with Ang Ⅱ induction were also suppressed by naringenin. As evidenced by atomic force microscope and radioligand receptor binding assay, naringenin inhibited Ang Ⅱ binding to AT1 receptor. In terms of TGF-β signaling, we found that feeding the mice with naringenin decreased the phosphorylation of Smad2 and ERK1/2 as well as the expression of TGF-β downstream genes. Besides, the serum level of TGF-β was also decreased by naringenin in the Fbn1C1039G/+ mice. Furthermore, we detected the effect of naringenin on platelet, a rich source of TGF-β, both in vivo and in vitro. And we found that naringenin markedly decreased the TGF-β level by inhibiting the activation of platelet.
CONCLUSION
Our study showed that naringenin has a protective effect on thoracic aortic aneurysm formation in Marfan syndrome by suppressing both AT1 and TGF-β signaling.
Angiotensin II/metabolism*
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Animals
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Aortic Aneurysm, Thoracic/prevention & control*
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Calcium/metabolism*
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Disease Models, Animal
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Elastin/metabolism*
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Fibrillin-1/metabolism*
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Flavanones
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Marfan Syndrome/metabolism*
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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Mice
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Mice, Inbred C57BL
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Protein Kinase C/metabolism*
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Receptor, Angiotensin, Type 1/metabolism*
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Transforming Growth Factor beta/metabolism*
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Transforming Growth Factors/metabolism*
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beta-Arrestins/metabolism*
8.Rapid Determination of Coating Film Thickness of Tianshu Tablets by Near Infrared Spectroscopy
Chun-yan XIA ; Fang-fang XU ; Xin ZHANG ; Bing XU ; Qing WANG ; Jie SHAO ; Pei-chao CUI ; Le-wei BAO ; Zhen-zhong WANG ; Wei XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(1):118-124
Objective::To investigate the feasibility of near-infrared spectroscopy for detecting the coating film thickness of Tianshu tablets. Method::Nine batches of Tianshu tablets were taken during the coating process. Then, their near-infrared diffuse reflection spectra were collected. The sample set was divided into calibration set and validation set by Kennard-Stone algorithm. The preprocessing method was selected. The synergy interval partial least squares (siPLS) and moving window partial least squares (mwPLS) were employed to screen the optimal spectral interval. And the corresponding quantitative calibration model of partial least squares (PLS) were established. Some evaluation parameters were adopted to assess the performance of the model. Result::The method of first derivative and Norris Derivative smoothing combined with standard normal variate transformation was suitable for processing the spectra. The optimal PLS model was established in the preferred band interval of siPLS. The correlation coefficient between the predicted value and the measured value of calibration set was 0.966, and the correlation coefficient between the predicted value and the measured value of validation set was 0.991.Both root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) values were small, which showed the fitness and predictive performance of the model were favorable. Conclusion::The near-infrared spectroscopy technique can be used to determine coating film thickness of Tianshu tablets with high accuracy, which provides technical supports for the in-line determination of coating thickness in the production process of traditional Chinese medicine tablets.
9.Identification of critical process parameters of Jinqing alcohol precipitation of Reduning Injection by big data.
Hui DU ; Bing XU ; Fang-Fang XU ; Xin ZHANG ; Qing WANG ; Chun-Yan XIA ; Le-Wei BAO ; Zhen-Zhong WANG ; Yan-Jiang QIAO ; Wei XIAO
China Journal of Chinese Materia Medica 2020;45(2):233-241
Lonicerae Japonicae Flos and Artemisiae Annuae Herba(LA or Jinqing) alcohol precipitation has various process parameters and complex process mechanism, and is one of the key units for manufacturing Reduning Injection. In order to identify the critical process parameters(CPPs) affecting the weight of the extract produced from the alcohol precipitation process, 259 batches of historical production data from 2017 to 2018 were collected, with a total of 829 318 data points. These data showed characteristics of large data, such as a large data volume, a low value density, and diverse sources. The data cleaning and feature extraction were first performed, and 48 feature variables were selected. The original data points were reduced to 9 936. Then, a combination of Pearson correlation analysis and grey correlation analysis were used to screen out 15 potential critical process parameters(pCPPs). After that, the partial least squares(PLS) was used in prediction of the weight of the extract, proving that the performance of predictive model based on 15 pCMAs is equivalent to that of predictive model based on 48 feature variables. The variable importance in projection(VIP) index was used to identify 9 CPPs, including 2 alcohol precipitation supernatant volume parameters, 4 initial extract weight parameters and 3 added alcohol volume parameters. As a result, the number of data points was 1 863, accounting for 0.28% of the original data. The big data analysis approach from a holistic point of view can effectively increase the value density of the original data. The critical process parameters obtained can help to accurately describe the quality transfer mechanism of the Jinqing alcohol precipitation process.
Alcohols
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Big Data
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Drugs, Chinese Herbal/chemistry*
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Solvents
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Technology, Pharmaceutical
10.Predictive model for hygroscopicity of contents in Guizhi Fuling Capsules.
Qing WANG ; Bing XU ; Fen WANG ; Fang-Fang XU ; Xin ZHANG ; Yong-Chao ZHANG ; Hui DU ; Chun-Yan XIA ; Le-Wei BAO ; Zhen-Zhong WANG ; Yan-Jiang QIAO ; Wei XIAO
China Journal of Chinese Materia Medica 2020;45(2):242-249
To control the risks of powder caking and capsule shell embrittlement of Guizhi Fuling Capsules, a predictive model for hygroscopicity of contents in Guizhi Fuling Capsules was built. A total of 90 batches of samples, including raw materials, intermediate powders and capsules, were collected during the manufacturing of Guizhi Fuling Capsules. According to the production sequence, 47 batches were used as the calibration set, and the properties of raw materials and the four intermediate powders were comprehensively characterized by the physical fingerprint. Then, the partial least squares(PLS) model was developed with the content hygroscopicity as the response variable. The variable importance in projection(VIP), variance inflation factor(VIF) and regression coefficients were used to screen out potential critical material attributes(pCMAs). As a result, five pCMAs from 54 physical parameters were screened out. Furthermore, different models were built by different combinations of pCMAs, and their predictive robustness of 43 batches was evaluated on the basis of the validation set. Finally, the tap density(D_c) of wet granules obtained from wet granulation and the angle of repose(α) of raw materials were identified as the critical material attributes(CMAs) affecting the hygroscopicity of the contents of Guizhi Fuling Capsules. The prediction model established with the two CMAs as independent variables had an average relative prediction error of 2.68% for samples in the validation set, indicating a good accuracy of prediction. This paper proved the feasibility of predictive modeling toward the control of critical quality attributes of Chinese medicine oral solid dosage(OSD). The combination of the continuous quality improvement, the industrial big data and the process modeling technique paved the way for the intelligent manufacturing of Chinese medicine oral solid preparations.
Capsules
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Drug Compounding
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Drugs, Chinese Herbal/chemistry*
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Powders
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Wettability

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