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.The influence of phase coding on streaking artifact of Star-volumetric interpolated body examination sequence
Jun LIU ; Jianwei WANG ; Lulu XU ; Hai XU ; Zhisheng LIN ; Liya JI
Journal of Practical Radiology 2025;41(5):857-860
Objective To discuss the mechanism of the streaking artifact of Star-volumetric interpolated body examination(Star-VIBE)sequence and the influence of phase coding on it.Methods Twenty-six volunteers underwent many times Star-VIBE sequences scanning with different phase coding(320,640,960,1 280,1 600).The severity of streaking artifact of images in different phase cod-ing groups was evaluated qualitatively.The signal-to-noise ratio(SNR)of muscle,thyroid and contrast-enhanced artery,contrast-to-noise ratio(CNR)between soft tissues,and CNR between muscle and contrast-enhanced artery of the images in different phase coding groups were evaluated quantitatively.Results In qualitative evaluation,with the number of phase coding increased,the streaking artifact decreased(H=83.022,P<0.005).In quantitative evaluation,SNRmuscle,SNRthyroid,SNRcontrast-enhanced artery and CNRcontrast-enhanced gradually increased with the increase of phase coding number(SNRmuscle:F=6.913,P<0.005;SNRthyroid:F=3.930,P=0.005;SNRcontrast-enhanced artery:F=6.980,P<0.005;CNRcontrast-enhanced:F=6.482,P<0.005),while CNRsoft tissue showed no statistical difference(F=1.114,P=0.339).Conclusion There is streaking artifact on the image of the Star-VIBE sequence,which can be reduced by increas-ing the number of phase coding appropriately.The most suitable phase coding is 960.
3.External Validation and Precision Drug Use of Pharmacokinetic Model of Lacosamide in Foreign Pediatric Populations
Huimin CHEN ; Yang WANG ; Jun WANG ; Zhisheng LIU
Herald of Medicine 2025;44(1):108-115
Objective To verify the predictive performance of the population pharmacokinetic(PPK)model of lacosamide in children reported abroad using real-world case data,the exposure-response relationship was analyzed,and the optimal dosing regimen was simulated.Methods The plasma concentration data and clinical data of 64 children with epilepsy aged 4-13.42 years after oral administration of lacosamide reached a steady state were collected,and the prediction accuracy of foreign models was investigated by goodness-of-fit diagram and intuitive prediction test.The relationship between the daily dose or trough concentration of lacosamide and the clinical efficacy was analyzed,and Monte Carlo simulation was used to evaluate and screen the optimal dosing regimen of lacosamide for different body weight stratification and combinations based on pharmacokinetic parameters.Results The external validation results show that the prediction accuracy of the PPK model for children abroad is good.The pharmacokinetic parameters of lacosamide monotherapy in children with epilepsy were as follows:absorption rate constant(ka)=(2.43±0.04)h-1,apparent volume of distribution(Vd/F)=(22.69±6.00)L,clearance rate(CL/F)=(1.25±0.27)L·h-1,half-life(t1/2)=(12.74±2.40)h.The distribution range of 5%-95%quantile of daily dose of clinically effective cases was 2.5-6.3 mg·kg-1·d-1,and the distribution range of 5%-95%of trough concentration was 1.9-6.7 mg·L-1.The simulation results showed that the optimized dosing regimen of lacosamide recommended in this study could increase the probability of drug concentration reaching the target and ensure the efficacy and tolerability of treatment.Conclusions The prediction performance of the PPK model of lacosamide in foreign children was verified,and the optimal dosing regimen was simulated based on this model,which can provide a reference for clinicians to individualize and rationalize the use of drugs.
4.CRTC2 attenuates cardiomyocyte hypertrophy by inhibiting cardiomyocyte ferroptosis
Zhaoyue WANG ; Hongyu ZHENG ; Yanxia WANG ; Yuanqin ZHAO ; Wei DENG ; Kun ZHOU ; Qian XU ; Huiting LIU ; Shao OUYANG ; Miao JIANG ; Zhongzhou YANG ; Zhisheng JIANG
Chinese Journal of Arteriosclerosis 2025;33(10):849-858
Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P<0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P<0.05 or P<0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P>0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P<0.05 or P<0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P<0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P<0.05 or P<0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.
5.Application research of nursing scheme based on self-regulation theory in patients with chronic pancreatitis
Dan WANG ; Zhisheng TAN ; Jialun XIE ; Xin KANG ; Huozhao RUAN ; Qiurong PAN ; Lihua WANG
Chinese Journal of Practical Nursing 2025;41(13):963-969
Objective:To explore the effect of nursing scheme based on self-regulation theory (SRT) on self-efficacy and quality of life of patients with chronic pancreatitis, and to provide basis for better promoting patients′ rehabilitation.Methods:Using a non-random historical control study, 55 patients with chronic pancreatitis admitted to The Fifth Affiliated Hospital of Southern Medical University from November 2021 to October 2022 were classified as the control group, and 55 patients with chronic pancreatitis admitted from November 2022 to October 2023 were classified as the research group. The control group received routine nursing intervention, while the research group received SRT-based nursing intervention. Both groups received a 3-month intervention. The General Self-Efficacy Scale, Exercise of Self-Care Agency Scale, Self Rated Abilities for Health Practices Scale, and Gastrointestinal Quality of Life Index were used to evaluate the self-efficacy, self-care ability, health behavior, and quality of life of two groups before and after the intervention, and statistical comparisons were made.Results:Both groups of patients completed the study. There were 28 males and 27 females in the control group. The age was (45.33 ± 12.26) years old. There were 30 males and 25 females in the research group. The age was (45.48 ± 12.61) years old. After the intervention, the score of the self-efficacy in the research group was (29.32 ± 2.88) points, which was higher than that in the control group (19.28 ± 1.95) points, the difference was significant ( t=21.41, P<0.05). The scores of self-care skills, self-responsibility, self-concept, health knowledge and the total score of the self-care ability in the research group were (35.32 ± 2.31), (22.85 ± 1.42), (25.88 ± 1.93), (64.32 ± 5.22), (148.34 ± 8.33) points respectively. They were all higher than those of the control group (28.66 ± 1.77), (17.22 ± 1.23), (18.67 ± 1.86), (60.08 ± 4.52), (124.56 ± 8.92) points. The differences were significant ( t values were 4.55-22.23, all P<0.05). The scores of exercise, nutrition, health responsibility, psychological comfort and the total score of the health behavior in the research group were (25.58 ± 1.41), (25.02 ± 2.03), (24.31 ± 2.34), (25.16 ± 1.63), (100.05 ± 7.36) points respectively. They were all higher than those of the control group (22.31 ± 2.03), (20.15 ± 2.82), (20.16 ± 2.89), (21.15 ± 2.17), (83.79 ± 7.84) points. The differences were significant ( t values were 8.28-11.21, all P<0.05). The scores of social activity, psychological state, physiological function, self-conscious symptoms and the total score of the quality of life in the research group were (16.78 ± 1.26), (17.03 ± 1.85), (22.43 ± 1.96), (17.09 ± 0.88), (73.41 ± 4.22) points respectively. They were all higher than those of the control group (15.32 ± 1.15), (15.34 ± 1.76), (20.86 ± 1.59), (16.03 ± 0.75), (67.52 ± 4.18) points. The differences were significant ( t values were 4.61-7.35, all P<0.05). Conclusions:SRT-based nursing scheme can effectively improve the self-efficacy and self-care ability of patients with chronic pancreatitis, and improve their health behavior and quality of life.
6.Summary of the best evidence for volume management in patients with continuous renal replacement therapy
Fang WANG ; Zhisheng ZHANG ; Anliu NIE ; Shaona LIAO ; Xiangfen SU
Chinese Journal of Practical Nursing 2025;41(33):2592-2599
Objective:To summarize the best evidence of volume management in patients with continuous renal replacement therapy, and to provid reference for clinical nursing practice.Methods:Comprehensive search clinical decisions, guidelines, expert consensus, group standards, systematic review and original study on volume management of patients with continuous renal replacement therapy in UpToDate, Cochrane Library, BMJ Best Practice, PubMed, Web of Science, CINAHL, Embase, Joanna Briggs Institute, National Guideline Clearinghouse, National Institute for Health and Clinical Excellence, Guideline International Network, Registered Nurses 'Association of Ontario, French Society of Anaesthesia and Intensive Care, International Society of Nephrology, Yimaitong, Chinese Nursing Association, China National Knowledge Infrastructure, Wanfang and other databases. The retrieval period was from the establishment of the database to April 6, 2024. Literature quality evaluation were conducted independently by researchers who had learned evidence-based nursing research, and the evidence was extracted and integrated.Results:A total of 17 articles were included, comprising 3 clinical decision-making studies, 2 guidelines, 9 expert consensus documents, 1 systematic review, 1 group standard, and 1 randomized controlled trial, and 31 pieces of evidence were summarized from six dimensions: team management, capacity assessment, capacity management objectives, process monitoring, capacity management measures and management of volume related complications.Conclusions:This study summarized the best evidence for the volume management of patients with continuous renal replacement therapy, and provided scientific and standardized basis for the guidance of volume management for clinical medical staff, suggesting that medical staff should selectively apply the best evidence according to the actual clinical situation.
7.Graduate destination and employment status of Chinese medical master's graduates: an analysis based on 2023 national survey
Jingrui LI ; Peiyao SHI ; Jinzhong JIA ; Wei JIANG ; Zhisheng LIANG ; Mengting ZHANG ; Zhiqiang WANG
Chinese Journal of Medical Education Research 2025;24(6):788-794
Objective:To understand the graduation destination of newly graduated medical master's students in China and analyze their employment status.Methods:A questionnaire survey was conducted on 15 942 medical master's students who graduated in 2023. Descriptive analysis, χ2 test, and Kruskal-Wallis rank-sum test were used to understand the current situation and differences in the graduation destinations, employment units, job positions, and starting salaries of different types of medical master's graduates. Results:The employment rate of medical master's graduates was 58.21% (9 280/15 942). In terms of graduation destinations, male graduates, professional degree holders, graduates from non-"Double First-Class" universities, and nursing majors had a high proportion of confirmed employment units. Male graduates, academic degree holders, graduates from "Double First-Class" universities, and basic medical science majors had a high proportion pursuing further studies domestically. In terms of employment, the highest proportion of medical master's graduates worked in hospitals (84.92%, 6 495/7 648) and the lowest proportion worked in primary-level medical and healthcare institutions (1.02%, 78/7 648). The majority (78.07%, 5 971/7 648) held professional technical positions. Starting salaries were relatively low and ranged between 3 001 and 5 000 yuan/month, accounting for 30.99% (2 370/7 648).Conclusions:The employment rate of medical master's graduates is low, with concentrated employment units and job positions, and there is a lack of talents in primary medical institutions. Colleges and universities and education management departments should adopt policy-driven approaches to support key demographic groups and encourage employment in primary healthcare. Training programs should be timely adjusted in response to market demands and focus on cultivating the comprehensive quality and job competence of medical master's graduates. Additionally, student-centered approaches should be used to strengthen the employment guidance and career planning services.
8.Angiotensin Ⅱ activates p53/SAT1 signaling pathway to induce ferroptosis in white adipocytes
Wei DENG ; Xiyan LIU ; Liyuan GUO ; Qian XU ; Kun ZHOU ; Yuanqin ZHAO ; Zhaoyue WANG ; Xiang LI ; Xin-mei DENG ; Xinyi QIN ; Zhong REN ; Zhisheng JIANG
Chinese Journal of Arteriosclerosis 2025;33(5):385-394
Aim To investigate the effect and mechanism of angiotensin Ⅱ(Ang Ⅱ)on ferroptosis in white adi-pocytes.Methods The 3T3-L1 preadipocytes were differentiated into white adipocytes by inducer stimulation.The experiment was divided into control group,Ang Ⅱ group,Ang Ⅱ+Fer-1(ferroptosis inhibitor)group and Ang Ⅱ+PFT-α(p53 inhibitor)group.Ang Ⅱ was used to treat cells.RT-qPCR and Western blot were used to detect the expression levels of ferroptosis factors and adipokines.JC-1 kit was used to detect mitochondrial membrane potential(MMP)level.Iron ion kit was used to detect intracellular iron content.Glutathione(GSH)kit was used to detect GSH content.Fer-1 and Ang Ⅱ were added to treat cells to detect the the changes of ferroptosis level.The expression of p53 and spermidine/spermine N1-acetyltransferase 1(SAT1)protein was detected.Subsequently,PFT-α and Ang Ⅱ were added to co-treat cells to detect the changes of p53 and SAT1 protein expression,and to observe the effect of inhibiting p53 expression on the expression levels of ferroptosis factors and adipokines.Results 3T3-L1 cells were successfully differentiated into white adipocytes by stimulator-induced differentiation.Ang Ⅱ induced ferroptosis in white adipocytes.RT-qPCR results showed that compared with control group,the mRNA expression of anti-ferroptosis factor glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11)and iron regulatory protein 1(IRP-1)was down-regulated in Ang Ⅱ group,and the mRNA expression of pro-ferroptosis factor acyl-CoA synthetase of long-chain family member 4(ACSL4)was up-regulated.Western blot results showed that compared with control group,the protein expression of SLC7A11 and GPX4 was down-regulated in Ang Ⅱ group,and the protein expression of ACSL4 was up-regulated.Ang Ⅱ treatment increased the content of intracellular iron ions and decreased the levels of GSH and MMP.Compared with Ang Ⅱ group,the mRNA expression of IRP-1 and SLC7A11 was up-regulated in Ang Ⅱ+Fer-1 group.Ang Ⅱ induced changes in the expression profile of adipokines in white adipocytes.Western blot results showed that compared with control group,the protein ex-pression of pro-inflammatory adipokine leptin(LEP),resistin(RETN),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)was up-regulated in Ang Ⅱ group,and the protein expression of anti-inflammatory adipokine adiponectin(AD-PN)and omentin 1(ITLN1)was down-regulated.In addition,Ang Ⅱ increased the protein expression of p53 and SAT1.Inhibition of p53 expression can improve the level of ferroptosis and adipokine expression in white adipocytes trea-ted with Ang Ⅱ.Western blot results showed that compared with Ang Ⅱ group,the protein expression of p53 and SAT1 was down-regulated in Ang Ⅱ+PFT-α group,the protein expression of SLC7A11 and GPX4 was up-regulated,and the protein expression of ACSL4 was down-regulated.The protein expression of ADPN was up-regulated in Ang Ⅱ+PFT-αgroup,and the protein expression of TNF-α,LEP and RETN was down-regulated.Conclusion Ang Ⅱ induces fer-roptosis in white adipocytes through activating the p53/SAT1 signaling pathway.
9.Application research of nursing scheme based on self-regulation theory in patients with chronic pancreatitis
Dan WANG ; Zhisheng TAN ; Jialun XIE ; Xin KANG ; Huozhao RUAN ; Qiurong PAN ; Lihua WANG
Chinese Journal of Practical Nursing 2025;41(13):963-969
Objective:To explore the effect of nursing scheme based on self-regulation theory (SRT) on self-efficacy and quality of life of patients with chronic pancreatitis, and to provide basis for better promoting patients′ rehabilitation.Methods:Using a non-random historical control study, 55 patients with chronic pancreatitis admitted to The Fifth Affiliated Hospital of Southern Medical University from November 2021 to October 2022 were classified as the control group, and 55 patients with chronic pancreatitis admitted from November 2022 to October 2023 were classified as the research group. The control group received routine nursing intervention, while the research group received SRT-based nursing intervention. Both groups received a 3-month intervention. The General Self-Efficacy Scale, Exercise of Self-Care Agency Scale, Self Rated Abilities for Health Practices Scale, and Gastrointestinal Quality of Life Index were used to evaluate the self-efficacy, self-care ability, health behavior, and quality of life of two groups before and after the intervention, and statistical comparisons were made.Results:Both groups of patients completed the study. There were 28 males and 27 females in the control group. The age was (45.33 ± 12.26) years old. There were 30 males and 25 females in the research group. The age was (45.48 ± 12.61) years old. After the intervention, the score of the self-efficacy in the research group was (29.32 ± 2.88) points, which was higher than that in the control group (19.28 ± 1.95) points, the difference was significant ( t=21.41, P<0.05). The scores of self-care skills, self-responsibility, self-concept, health knowledge and the total score of the self-care ability in the research group were (35.32 ± 2.31), (22.85 ± 1.42), (25.88 ± 1.93), (64.32 ± 5.22), (148.34 ± 8.33) points respectively. They were all higher than those of the control group (28.66 ± 1.77), (17.22 ± 1.23), (18.67 ± 1.86), (60.08 ± 4.52), (124.56 ± 8.92) points. The differences were significant ( t values were 4.55-22.23, all P<0.05). The scores of exercise, nutrition, health responsibility, psychological comfort and the total score of the health behavior in the research group were (25.58 ± 1.41), (25.02 ± 2.03), (24.31 ± 2.34), (25.16 ± 1.63), (100.05 ± 7.36) points respectively. They were all higher than those of the control group (22.31 ± 2.03), (20.15 ± 2.82), (20.16 ± 2.89), (21.15 ± 2.17), (83.79 ± 7.84) points. The differences were significant ( t values were 8.28-11.21, all P<0.05). The scores of social activity, psychological state, physiological function, self-conscious symptoms and the total score of the quality of life in the research group were (16.78 ± 1.26), (17.03 ± 1.85), (22.43 ± 1.96), (17.09 ± 0.88), (73.41 ± 4.22) points respectively. They were all higher than those of the control group (15.32 ± 1.15), (15.34 ± 1.76), (20.86 ± 1.59), (16.03 ± 0.75), (67.52 ± 4.18) points. The differences were significant ( t values were 4.61-7.35, all P<0.05). Conclusions:SRT-based nursing scheme can effectively improve the self-efficacy and self-care ability of patients with chronic pancreatitis, and improve their health behavior and quality of life.
10.Summary of the best evidence for volume management in patients with continuous renal replacement therapy
Fang WANG ; Zhisheng ZHANG ; Anliu NIE ; Shaona LIAO ; Xiangfen SU
Chinese Journal of Practical Nursing 2025;41(33):2592-2599
Objective:To summarize the best evidence of volume management in patients with continuous renal replacement therapy, and to provid reference for clinical nursing practice.Methods:Comprehensive search clinical decisions, guidelines, expert consensus, group standards, systematic review and original study on volume management of patients with continuous renal replacement therapy in UpToDate, Cochrane Library, BMJ Best Practice, PubMed, Web of Science, CINAHL, Embase, Joanna Briggs Institute, National Guideline Clearinghouse, National Institute for Health and Clinical Excellence, Guideline International Network, Registered Nurses 'Association of Ontario, French Society of Anaesthesia and Intensive Care, International Society of Nephrology, Yimaitong, Chinese Nursing Association, China National Knowledge Infrastructure, Wanfang and other databases. The retrieval period was from the establishment of the database to April 6, 2024. Literature quality evaluation were conducted independently by researchers who had learned evidence-based nursing research, and the evidence was extracted and integrated.Results:A total of 17 articles were included, comprising 3 clinical decision-making studies, 2 guidelines, 9 expert consensus documents, 1 systematic review, 1 group standard, and 1 randomized controlled trial, and 31 pieces of evidence were summarized from six dimensions: team management, capacity assessment, capacity management objectives, process monitoring, capacity management measures and management of volume related complications.Conclusions:This study summarized the best evidence for the volume management of patients with continuous renal replacement therapy, and provided scientific and standardized basis for the guidance of volume management for clinical medical staff, suggesting that medical staff should selectively apply the best evidence according to the actual clinical situation.

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