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.

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.

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.

Aim To investigate the effect of hydrogen sulfide on macrophage calcification and its underlying mo-lecular mechanisms.Methods Oil red O staining was used to observe intracellular lipid accumulation,and von Kossa staining and atomic absorption spectroscopy were used for morphological and quantitative analysis of calcium deposition and intracellular calcium content in a mononuclear macrophage calcification model.Western blot and RT-PCR were used to detect the mRNA and protein expression of osteopontin(OPN)at different doses and treatment times of hydrogen sulfide.At the same time,Western blot was used to detect the expression changes of early growth response factor 1(EGR1),endo-plasmic reticulum stress-related markers C/EBP homologous protein(CHOP)and glucose-regulated protein 78(GRP78).Reactive oxygen species levels were evaluated by fluorescence probe staining,and the effect of hydrogen sulfide on macro-phage calcification was evaluated by combining von Kossa staining and calcium ion fluorescence probe staining.The mo-lecular mechanisms of hydrogen sulfide affecting macrophage calcification were explored by interfering with EGR1 expression and using endoplasmic reticulum stress inhibitor 4-phenylbutyric acid(4-PBA).Results Compared with oxidized low density lipoprotein(ox-LDL)group,β-glycerophosphate(β-GP)+40 g/L ox-LDL group showed a significant increase in intracellular lipid accumulation,while hydrogen sulfide significantly inhibited macrophage calcification in a con-centration-and time-dependent manner.Compared with the β-GP+ox LDL group,the most significant effect was observed after incubation with 100 μmol/L NaHS for 4 days.The hydrogen sulfide group showed a 66％decrease in intracellular calcium content(P＜0.01),a 71％decrease in intercellular calcium deposition(P＜0.01),and a 50％and 48％decrease in OPN mRNA and protein expression,respectively(P＜0.05).Hydrogen sulfide treatment upregulated the ex-pression of EGR1 by 21％,while downregulating the expression of CHOP and GRP78 by 58％and 59％,respectively(P＜0.01).The endoplasmic reticulum stress inhibitor 4-PBA could downregulate OPN expression by 73％(P＜0.01),while interfering with EGR1 expression completely counteracts the inhibitory effect of hydrogen sulfide on OPN expression and calcium deposition(P＜0.01).Conclusion Hydrogen sulfide significantly inhibits macrophage calcification by upregulating EGR1 expression and suppressing endoplasmic reticulum stress.

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).

Aim To investigate the effect of hydrogen sulfide on macrophage calcification and its underlying mo-lecular mechanisms.Methods Oil red O staining was used to observe intracellular lipid accumulation,and von Kossa staining and atomic absorption spectroscopy were used for morphological and quantitative analysis of calcium deposition and intracellular calcium content in a mononuclear macrophage calcification model.Western blot and RT-PCR were used to detect the mRNA and protein expression of osteopontin(OPN)at different doses and treatment times of hydrogen sulfide.At the same time,Western blot was used to detect the expression changes of early growth response factor 1(EGR1),endo-plasmic reticulum stress-related markers C/EBP homologous protein(CHOP)and glucose-regulated protein 78(GRP78).Reactive oxygen species levels were evaluated by fluorescence probe staining,and the effect of hydrogen sulfide on macro-phage calcification was evaluated by combining von Kossa staining and calcium ion fluorescence probe staining.The mo-lecular mechanisms of hydrogen sulfide affecting macrophage calcification were explored by interfering with EGR1 expression and using endoplasmic reticulum stress inhibitor 4-phenylbutyric acid(4-PBA).Results Compared with oxidized low density lipoprotein(ox-LDL)group,β-glycerophosphate(β-GP)+40 g/L ox-LDL group showed a significant increase in intracellular lipid accumulation,while hydrogen sulfide significantly inhibited macrophage calcification in a con-centration-and time-dependent manner.Compared with the β-GP+ox LDL group,the most significant effect was observed after incubation with 100 μmol/L NaHS for 4 days.The hydrogen sulfide group showed a 66％decrease in intracellular calcium content(P＜0.01),a 71％decrease in intercellular calcium deposition(P＜0.01),and a 50％and 48％decrease in OPN mRNA and protein expression,respectively(P＜0.05).Hydrogen sulfide treatment upregulated the ex-pression of EGR1 by 21％,while downregulating the expression of CHOP and GRP78 by 58％and 59％,respectively(P＜0.01).The endoplasmic reticulum stress inhibitor 4-PBA could downregulate OPN expression by 73％(P＜0.01),while interfering with EGR1 expression completely counteracts the inhibitory effect of hydrogen sulfide on OPN expression and calcium deposition(P＜0.01).Conclusion Hydrogen sulfide significantly inhibits macrophage calcification by upregulating EGR1 expression and suppressing endoplasmic reticulum stress.

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).

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.

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.

Objective:To investigate the enrollment scale and distribution of Master's Degree in Pediatrics programs in China, and to provide a reference for promoting pediatric education and disciplinary development.Methods:Data on colleges and universities authorized to award Master's Degree in Pediatrics in 2023 were collected, sorted, and analyzed for the number, structure, distribution, and enrollment scale and direction of these institutions using descriptive statistics.Results:Among the 117 clinical medicine academic master's degree programs in China, 72 enroll pediatric academic master's degree candidates, with an enrollment of 260 students. Among the 120 master's degree programs in clinical medicine, 104 enroll professional master's degree candidates, enrolling 1 195 students. Enrollment is mainly concentrated in East China, "non-double first-class" colleges and universities, medical colleges and universities with subject level B, and enrollment is carried out in the direction of secondary disciplines.Conclusions:The number of colleges and universities authorized to award Master's Degree in Pediatrics was small, and the distribution of these colleges and universities was unbalanced. The enrollment scale was small and the orientation of Professional Master's Degree was not reasonable. Some colleges and universities were authorized to award Master's Degree in Pediatrics, but did not enroll any students. It is suggested to increase the number of colleges and universities authorized to award Master's Degree in Pediatrics and strengthen the staffing of pediatric departments. The aim is to expand the enrollment scale of candidates for Master's Degree in Pediatrics, improving the differential training of candidates for Academic Master's Degree and Professional Master's Degree, and attach importance to the construction of pediatrics.