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 investigate the clinical efficacy of hepatic artery ringed and restriction operation-associating liver partition and portal vein ligation for staged hepatectomy (HARO-ALPPS) in the treatment of giant hepatocellular carcinoma.Methods The retrospective and descriptive study was conducted.Clinical data of a 45-year-old male patient with giant hepatocellular carcinoma who was admitted to the First Affiliated Hospital of Guangxi Medical University in July 2018 were collected.In the first stage operation,right portal vein ligation+ in situ liver partition + right hepatic artery ringed operation was performed on the patient.In the second stage operation,right hemihepatectomy was performed on the patient.Observation indicators:(1) surgical and postoperative situations of the first stage operation;(2) surgical and postoperative situations of the second stage operation;(3) postoperative pathological examination;(4) changes in future liver remnant (FLR) and tumor volume;(5) perioperative hemodynamic changes of right hepatic artery,proper hepatic artery and left hepatic artery;(6) perioperative hemodynamic changes of left-portal vein and main portal vein;(7) follow-up.Follow-up using outpatient examination was performed to detect the prognosis of patients up to February 2019.Count data were described as absolute number.Results (1) Surgical and postoperative situations of the first stage operation:the patient underwent right portal vein ligation+ in situ liver partition+ right hepatic artery ringed operation successfully.The operation time and volume of intraoperative blood loss were 376 minutes and 400 mL.Inflammatory indicators including body temperature,white blood cells (WBC),C-reactive protein,procalcitonin,and liver function indices including total bilirubin (TBil),albumin (Alb),alanine aminotransferase (ALT),aspartate aminotransferase (AST),ascites,indocyanine green retention rate at15 min (ICG R15),score of model for end-stage liver disease (MELD) before the second stage operation were improved after symptomatic supportive treatment.Prothrombin time (PT) was in the normal range after the first stage operation.There was no complication of Clavien-Dindo classification Ⅱ or above.(2) Surgical and postoperative situations of the second stage operation:the patient underwent right hemihepatectomy successfully.The operation time and volume of intraoperative blood loss were 322 minutes and 900 mL.The patient received 300 mL of fresh frozen plasma infusion.Inflammatory indicators including body temperature,C-reactive protein,and liver function indices including Alb,ALT,AST,ascites,were recoved to normal level after symptomatic supportive treatment.WBC,procalcitonin,TBil,and PT were in the normal range.There was no complication of Clavien-Dindo classification Ⅱ or above.(3) Postoperative pathological examination:① Ⅱ stage hepatocellular carcinoma was confirmed,mass-like type,with tissue necrosis and microvascluar invasion.There was no distal metastasis and tumor did not invade liver capsule or surgical margin.Ishak score of surrounding tissues was 3 in the inflammation and 2 in the fibrosis.② Chronic inflammation was detected in the gallbladder mucosa.③ Reactive hyperplasia was found in the 2 lymph nodes of the group 8.④ One in the group 12 lymph nodes showed reactive hyperplasia.Immunohistochemistry showed positive Glypican-3,Hepatocyte,Arginase-1,NM23,weakly positive vascular endothelial growth factor,and negative Ki-67,vascular endothelial cell marker CD34,biliary epithelial marker CK19 and CK 7,tumor suppressor gene P21 and P23.(4) Changes in FLR and tumor volume:FLR was 565 mL and 580 mL at the 5th and 14th day after the first stage operation respectively,accounting for 54％ and 57％ of total liver volume.The FLR to body weight ratio was 0.96 and 0.98,and the growth rate of FLR was 194％ and 202％.Tumor volume was 1 210 mL and 1 297 mL at the 5th and 14th day after the first stage operation respectively.Tumor necrosis volume was 635 mL and 500 mL at the 5th and 14th day after the first stage operation respectively.At the 5th and 14th day after the first stage operation,the liver CT examination showed that HARO was successfully underwent and the blood supply of remnant liver was good.Preoperative CT aothgraphy (CTA) examination showed that the right hepatic tumor had rich arterial blood supply.At the 5th day after the first stage operation,the CTA examination confirmed the ringed site of right hepatic artery,and the blood supply of the tumor gradually decreased.At the 14th day after the first stage operation,CTA examination showed significant decrease in the blood supply of liver tumors.Liver CT examination showed rich supply of the remnant liver and the liver volume of 829 mL at the 7th day after the second stage operation.(5) Perioperative hemodynamic changes of the right hepatic artery,proper hepatic artery and left hepatic artery.① Blood flow of right hepatic artery was 224.3,574.7,827.5,222.7,153.0,282.5,279.1,247.9 and 150.2 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and before right hepatic artery ringed and restriction,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th and 7th day after the first stage operation.Blood flow of right hepatic artery in the second stage operation was 505.0 mL/min.② Blood flow of proper hepatic artery was 399.7,793.5,830.5,1 075.4,784.7.5,821.2,722.8,467.4 and 555.4 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and before right hepatic artery ringed and restriction,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th and 7th day after the first stage operation.Blood flow of proper hepatic artery was 505.0,473.3,158.5,627.0,103.8 and 139.8 mL/min before right hepatectomy in the second stage operation,after right hepatectomy,at the 1st,3th and 5th day after the second operation,respectively.③ Blood flow of left hepatic artery was 147.5,13.8,19.4,16.2,62.1,93.9,67.1,30.8 and 106.1 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and before right hepatic artery ringed and restriction,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th,7th and 10th day after the first stage operation.Blood flow ot left hepatic artery was 52.0,43.2,112.4,103.6,80.7 and 56.1 mL/min before right hepatectomy in the second stage operation,after right hepatectomy,at the 1st,3th and 5th day after the second operation,respectively.(6) Perioperative hemodynamic changes of left-portal vein and main portal vein.① Blood flow of left portal vein was 552.6,181.2,412.2,320.0,1 777.7,1 284.7,749.5 and 484.2 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th,7th and 10th day after the first stage operation,respectively.Blood flow of left portal vein was 793.3,979.0,485.2,1 042.5,803.5 and 548.3 mL/min before right hepatectomy in the second stage operation,after right hepatectomy,at the 1st,3th,5th and 7th day after the second operation respectively.② Blood flow of main portal vein was 1 186.0,696.7,833.7,431.7,1 319.1,668.4,890.7,550.8 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th,7th and 10th day after the first stage operation,respectively.Blood flow of main portal vein was 846.4,937.4,891.2,1 671.0,2 697.8,and 1 230.0 mL/min before right hepatotectomy in the second stage operation,after right hepatectomy,at the 1st,3th,5th and 7th day after the second stage operation,respectively.(7) Follow up:the patient was followed up for 6 months and survived well,with Child A of liver function and normal alpha fetoprotein level.Liver contrast CT examination showed increase in the remnant liver,good blood supply,and no tumor recurrence.The FLR was 727 mL at the 2 months after operation.Conclusion For patients with giant hepatocellular carcinoma,HARO-ALPPS can be performed to decrease blood supply of tumor,increase tumor necrosis area,and reduce the incidence of intrahepatic arteriovenous fistula,which ensure blood supply of remnant liver hyperplasia.

Objective To investigate the changes of serum insulin-like growth factor-2 (IGF-2) and insulin-link growth factor binding protein-3(IGFBP-3) in the patients with ovarian cancer before and after operation,and evaluate their clinical significance.MethodsThe contents of serum IGF-2 and IGFBP-3 in 82 patients with ovarian cancer were detected by ELISA before and after operation and compared with that in health controls.ResultsThe contents of IGF-2 in the patients before operation were significantly higher than that in control group[(101.5±22.2)ng/ml,(49.3±15.6)ng/ml vs (69.6±17.7)ng/ml,(23.9±11.3)ng/ml,t＝3.74,2.85,P＜0.05].The contents of IGFBP-3[(39.8±11.1)ng/ml]in the patients before operation were significantly lower than that in control group[(55.8±19.2)ng/ml](t′＝4.49,P＜0.05).There was significant correlation between the contents with lymph node metastasis and clinical stage[(107.5±24.0)ng/ml,(41.7±16.9)ng/ml vs (91.6±17.7)ng/ml,(56.9±19.1)ng/ml;(103.4±27.2)ng/ml,(50.2±16.6)ng/ml vs (86.6±12.3)ng/ml,(41.1±17.1)ng/ml,t＝2.83,2.37,2.48,3.32,P＜0.05).The contents of IGF-2 was significantly decreased,and IGFBP-3 was significantly increased in patients after radical operation [(86.6±12.3)ng/ml,(41.1±17.1)ng/ml vs (103.2±26.0)ng/ml,(45.3±14.9)ng/ml,t′＝3.46,t＝2.67,P＜0.05].But there was no significant difference on the level of IGF-2 and IGFBP-3 before and after palliative resection(P＞0.05).ConclusionsThe contents of serum IGF-2 and IGFBP-3 are closely related to tumor invasion,metastasis and clinical stage.Dynamic determination of the contents of serum IGF-2 and IGFBP-3 may be an important index for evaluation of invasion,metastasis,efficacy and prognosis for the patients with ovarian cancer.