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.

BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.

Objective:To construct analytical dimensions for policy texts related to the pilot work of Health Impact Assessment (HIA) system in Zhejiang Province and conduct quantitative analysis, thereby providing references for improving the pilot work.Methods:Policy texts issued by Zhejiang Province between February 11, 2018, and February 29, 2024, which involved HIA content, were selected. The policy instruments theory was employed to construct an analytical framework around the dimensions of policy instruments, policy objectives, policy actors, and the interactions between policy instruments and policy objectives, and between policy instruments and policy actors. Based on this framework, a combination of literature analysis and content analysis was used to conduct a multi-dimensional quantitative analysis of the policy texts related to the pilot work of HIA system in Zhejiang Province.Results:Fifty core policy texts were included and 1 588 codes were obtained. In terms of policy instruments, environmental-type instruments were the most widely used (852 items), with internal responsibilities and methodological measures being the most frequently used; supply-type instruments were the second most used (459 items), with mechanism improvement being the most frequently used; demand-type instruments were the least used (277 items), with multi-stakeholder participation being the most frequently used. In terms of policy objectives, the objective of system construction dominated (701 articles, accounting for 56.45%), while the proportion of policy coverage, evaluation technology, and effectiveness evaluation was relatively low. In terms of policy subjects, the Party committee and government were the main policy subjects (434 articles, accounting for 39.20%), followed by health departments and public policy-making departments, while the proportion of public health institutions and social forces was extremely low. In the interaction between policy instruments and policy objectives, policy coverage, system construction, and effectiveness evaluation objectives all responded most frequently to environmental-type instruments, while the evaluation technology objectives responded more frequently to supply-type instruments. In the interaction between policy instruments and policy subjects, the Party committee and government played a dominant role in the use of policy instruments, with the health department and public policy-making department in the middle.Conclusions:The pilot work of the HIA system in Zhejiang Province presented a " environment-driven, system-construction-priority, Party-committee-and-government-led" policy characteristic. The main challenges were the imbalanced structure of policy instruments, insufficient synergy among policy objectives, and the need for greater participation of multiple stakeholders.

Objective To explore the anti-inflammatory properties of the ethyl acetate extract(ETCB)derived from Trollius chinensis Bge.using in vitro RAW264.7 cells stimulated with lipopolysaccharide and an in vivo mouse auricle model induced by xylene.Utilizing UHPLC-Q-TOF-MS(LC-MS)and network pharmacology,the components of ETCB were analyzed,and its anti-inflammatory mechanisms were preliminarily explored.Methods The anti-inflammatory activity of various solvent extracts of Trollius chinensis Bge.was assessed through the Griess assay.The impact of ETCB on the production of TNF-α and IL-6 in RAW264.7 cells induced by lipopolysaccharide was evaluated using ELISA.Real-time qPCR was conducted to determine the effect of ETCB on the expression levels of inflammatory factors such as TNF-α,IL-6,and iNOS in cells.The anti-inflammatory efficacy was further validated in a xylene-induced ear inflammation mouse model by measuring ear swelling and tissue levels of IL-6 and TNF-α.The composition of ETCB was analyzed using LC-MS.Network pharmacology was employed to screen for effective components,targets,and pathways involved in the anti-inflammatory effects of Trollius chinensis Bge.,followed by molecular docking verification between core components and targets.Results ETCB demonstrated the most potent inhibitory effect on NO production in RAW264.7 cells stimulated by lipopolysaccharide,indicating its primary role in the anti-inflammatory activity of Trollius chinensis Bge..ETCB significantly reduced TNF-α and IL-6 levels in inflammatory cells(P<0.01)and inhibited the mRNA expression of TNF-α,IL-6,and iNOS.In the xylene-induced mouse ear inflammation model,ETCB effectively alleviated ear swelling and decreased tissue levels of TNF-α and IL-6.LC-MS analysis identified 30 chemical components in ETCB,including 21 flavonoids,7 organic acids,1 polysaccharide,and 1 anthocyanin.Network pharmacology prediction and screening revealed TNF,Akt1,PTGS2,EGFR,SRC,and MMP9 as core targets,with hydroxyquercetin,lignin from fragrant leaves,zeaxanthin from willows,plantain,thistle,and sophora flavins as key anti-inflammatory active ingredients.The molecular docking analysis revealed positive interactions,characterized by favorable binding energy,between the active components and key targets.Conclusion ETCB demonstrates strong anti-inflammatory properties both inside and outside the body,functioning through various targets and pathways.This establishes a basis for deeper understanding of the anti-inflammatory mechanism of Trollius chinensis Bge.

Objective To explore the anti-inflammatory properties of the ethyl acetate extract(ETCB)derived from Trollius chinensis Bge.using in vitro RAW264.7 cells stimulated with lipopolysaccharide and an in vivo mouse auricle model induced by xylene.Utilizing UHPLC-Q-TOF-MS(LC-MS)and network pharmacology,the components of ETCB were analyzed,and its anti-inflammatory mechanisms were preliminarily explored.Methods The anti-inflammatory activity of various solvent extracts of Trollius chinensis Bge.was assessed through the Griess assay.The impact of ETCB on the production of TNF-α and IL-6 in RAW264.7 cells induced by lipopolysaccharide was evaluated using ELISA.Real-time qPCR was conducted to determine the effect of ETCB on the expression levels of inflammatory factors such as TNF-α,IL-6,and iNOS in cells.The anti-inflammatory efficacy was further validated in a xylene-induced ear inflammation mouse model by measuring ear swelling and tissue levels of IL-6 and TNF-α.The composition of ETCB was analyzed using LC-MS.Network pharmacology was employed to screen for effective components,targets,and pathways involved in the anti-inflammatory effects of Trollius chinensis Bge.,followed by molecular docking verification between core components and targets.Results ETCB demonstrated the most potent inhibitory effect on NO production in RAW264.7 cells stimulated by lipopolysaccharide,indicating its primary role in the anti-inflammatory activity of Trollius chinensis Bge..ETCB significantly reduced TNF-α and IL-6 levels in inflammatory cells(P<0.01)and inhibited the mRNA expression of TNF-α,IL-6,and iNOS.In the xylene-induced mouse ear inflammation model,ETCB effectively alleviated ear swelling and decreased tissue levels of TNF-α and IL-6.LC-MS analysis identified 30 chemical components in ETCB,including 21 flavonoids,7 organic acids,1 polysaccharide,and 1 anthocyanin.Network pharmacology prediction and screening revealed TNF,Akt1,PTGS2,EGFR,SRC,and MMP9 as core targets,with hydroxyquercetin,lignin from fragrant leaves,zeaxanthin from willows,plantain,thistle,and sophora flavins as key anti-inflammatory active ingredients.The molecular docking analysis revealed positive interactions,characterized by favorable binding energy,between the active components and key targets.Conclusion ETCB demonstrates strong anti-inflammatory properties both inside and outside the body,functioning through various targets and pathways.This establishes a basis for deeper understanding of the anti-inflammatory mechanism of Trollius chinensis Bge.

Objective:To construct analytical dimensions for policy texts related to the pilot work of Health Impact Assessment (HIA) system in Zhejiang Province and conduct quantitative analysis, thereby providing references for improving the pilot work.Methods:Policy texts issued by Zhejiang Province between February 11, 2018, and February 29, 2024, which involved HIA content, were selected. The policy instruments theory was employed to construct an analytical framework around the dimensions of policy instruments, policy objectives, policy actors, and the interactions between policy instruments and policy objectives, and between policy instruments and policy actors. Based on this framework, a combination of literature analysis and content analysis was used to conduct a multi-dimensional quantitative analysis of the policy texts related to the pilot work of HIA system in Zhejiang Province.Results:Fifty core policy texts were included and 1 588 codes were obtained. In terms of policy instruments, environmental-type instruments were the most widely used (852 items), with internal responsibilities and methodological measures being the most frequently used; supply-type instruments were the second most used (459 items), with mechanism improvement being the most frequently used; demand-type instruments were the least used (277 items), with multi-stakeholder participation being the most frequently used. In terms of policy objectives, the objective of system construction dominated (701 articles, accounting for 56.45%), while the proportion of policy coverage, evaluation technology, and effectiveness evaluation was relatively low. In terms of policy subjects, the Party committee and government were the main policy subjects (434 articles, accounting for 39.20%), followed by health departments and public policy-making departments, while the proportion of public health institutions and social forces was extremely low. In the interaction between policy instruments and policy objectives, policy coverage, system construction, and effectiveness evaluation objectives all responded most frequently to environmental-type instruments, while the evaluation technology objectives responded more frequently to supply-type instruments. In the interaction between policy instruments and policy subjects, the Party committee and government played a dominant role in the use of policy instruments, with the health department and public policy-making department in the middle.Conclusions:The pilot work of the HIA system in Zhejiang Province presented a " environment-driven, system-construction-priority, Party-committee-and-government-led" policy characteristic. The main challenges were the imbalanced structure of policy instruments, insufficient synergy among policy objectives, and the need for greater participation of multiple stakeholders.

Objective:To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients.Methods:A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis.Results:After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations ( HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations ( HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations ( HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations ( HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations ( HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions:PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.

Objective: To investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. Methods: A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. Results: A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. Conclusions WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

Objective:To analyze and verify the expression of ISL1 gene in myocardial infarction, and explore its mechanism of action in myocardial infarction.Methods:By analyzing the chip expression profile data in the GEO database, the expression characteristics of the ISL1 gene in myocardial infarction, as well as the highly co expressed related genes and enriched pathway functions of the ISL1 gene, were identified. Patients with myocardial infarction and their healthy controls were included, and the expression of genes such as ISL1 and GRIN2D was verified using real-time polymerase chain reaction (RT-PCR).Results:The expression level of ISL1 gene in myocardial infarction samples was higher than that in the control group samples. In the GSE59867 and GSE29111 datasets, there are a total of 152, 231, and 329 intersections of the top 2000, top 2500, and top 3000 related genes, respectively. The functional annotation of co-expressed genes revealed that intersection genes were closely related to organ development, matrix protein formation, epithelial cell differentiation, and the activity of related signaling pathways during embryonic development. Finally, in the construction of the ISL1 related ceRNA regulatory network, 12 genes were located in the ISL1 top 2000 related mating set, and together with miRNAs, they participated in the formation of 21 pairs of miRNA-mRNA. And through multiple queues, the key regulatory gene was identified as GRIN2D, which competitively bound to multiple miRNAs with ISL1 and its expression was highly negatively correlated with ISL1 in two independent datassets ( r=-0.52, -0.41). The RT-PCR results showed that the expression levels of miR-128-3p, miR 27a-3p, and miR-27b-3p in the acute myocardial infarction group were lower than those in the control group, while the expression levels of ISL1 and GRIN2D were higher than those in the control group (all P<0.01). Conclusions:ISL1 may play a protective role in myocardial infarction by participating in the formation of matrix proteins, differentiation of epithelial cells, and activity of related signaling pathways.

Objective To retrieve,evaluate and summarize the relevant evidence on malnutrition management among maintenance hemodialysis(MHD)patients to provide clinical medical staff with evidence-based guidelines for managing malnutrition in MHD patients.Methods Using the"6S"pyramid model of evidence,We searched UpToDate,BMJ best clinical practice,the Australian JBI evidence-based health care centre database(JBI),Medive,the International Guidelines Collaborative Network(GIN),Agency for Healthcare Research and Quality Network,the UK National Institute of Clinical Medicine Guidance Library(NICE),Scottish Inter-College Guide Collaboration network,the Ontario Registered Nurses Association(RNAO),Guidelines Network of International Society of Nephrology,American Nephrology Foundation Guidenet,British Nephrology Society,Society of Nephrology,Chinese Medical Association,Improving Kidney Disease Outcomes Worldwide,International Society of Renal Nutrition and Metabolism,American Society for Parenteral Enteral Nutrition,European Society for Clinical Nutrition and Metabolism,Chinese Nutrition Society,PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang,VIP and CBM,to collect relevant guidelines,expert consensus,clinical decision,evidence summary,recommended practice,best practice,systematic evaluation and clinical practice,from the establishment to the date of April 10th,2023,for literature on malnutrition management of MHD patients.The literature included guidelines,expert consensuses,clinical decision-making studies,evidence summaries,recommended practices,best practices,and systematic reviews.Two researchers independently evaluated,extracted,and integrated the evidence.The evidence was graded by the evidence pre-grading system of the Evidence-based Healthcare Center of Joanna Briggs Institute(JBI).Results A total of 16 articles were included and summarized,comprising 5 guidelines,3 expert consensuses,1 clinical decision-making study,1 evidence summary,and 6 systematic reviews.Thirty-nine pieces of the best evidence were integrated,covering 5 key aspects(39 evidences):screening and assessment,nutritional requirements,nutritional supplement,other interventions,and monitoring and education.Conclusions The best evidence summary of malnutrition management among MHD patients in this study is scientifically rigorous and systematic.Clinical medical staff can use the best evidence to develop personalized malnutrition management programs for MHD patients.