Objective:It is of great significance to analyze the expression characteristics of immune-related genes in pancreatic cancer and their relationship with prognosis,construct and verify a reliable prognostic model,and explore prognostic methods of pancreatic cancer from the perspective of immune microenvironment.Methods:GSEA enrich-ment analysis of differentially expressed genes in pancreatic cancer was performed to identify key immune-related pathways and genes.The genes involved in the immune pathway were screened through the STRING database and combined with univariate Cox regression and LASSO regression analysis.Three key genes,RIPK2,IRAK2 and CXCL11,were finally identified to construct the prognostic model.The accuracy of the model was evaluated using ROC curves and calibration curves,and verified in an independent verification set(GSE57495).At the same time,the expression pat-terns of key genes in the immune microenvironment were analyzed by single-cell RNA sequencing,and the expression levels of these genes were verified in pancreatic cancer cell lines by RT-qPCR.Results:The expressions of RIPK2,IRAK2 and CXCL11 in pancreatic cancer cell lines were higher than those in normal pancreatic cancer cells(P<0.05).The model based on these three genes divided the patients into a high-risk group(n=87)and a low-risk group(n=89),and the difference in survival time between the high-risk group and the low-risk group was statistically significant(P<0.001).Risk score was correlated with G stage,N stage and tumor residue(P<0.01).Single-cell analysis showed that the ex-pression of these genes was highest in tumor-associated macrophages(mean>0.5)and correlated with regulatory T cells and macrophage infiltration(P<0.05).Multivariate analysis showed that risk score was correlated with overall sur-vival after adjusting for clinical factors(P=0.0014).Conclusion:Based on three key immune-related genes(RIPK2,IRAK2 and CXCL11),we successfully constructed a model to accurately predict the prognosis of pancreatic cancer pa-tients,revealing the important role of these genes in the tumor immune microenvironment,and providing new insights and theoretical basis for pancreatic cancer prognosis assessment and immunotherapy research.

Objective:It is of great significance to analyze the expression characteristics of immune-related genes in pancreatic cancer and their relationship with prognosis,construct and verify a reliable prognostic model,and explore prognostic methods of pancreatic cancer from the perspective of immune microenvironment.Methods:GSEA enrich-ment analysis of differentially expressed genes in pancreatic cancer was performed to identify key immune-related pathways and genes.The genes involved in the immune pathway were screened through the STRING database and combined with univariate Cox regression and LASSO regression analysis.Three key genes,RIPK2,IRAK2 and CXCL11,were finally identified to construct the prognostic model.The accuracy of the model was evaluated using ROC curves and calibration curves,and verified in an independent verification set(GSE57495).At the same time,the expression pat-terns of key genes in the immune microenvironment were analyzed by single-cell RNA sequencing,and the expression levels of these genes were verified in pancreatic cancer cell lines by RT-qPCR.Results:The expressions of RIPK2,IRAK2 and CXCL11 in pancreatic cancer cell lines were higher than those in normal pancreatic cancer cells(P<0.05).The model based on these three genes divided the patients into a high-risk group(n=87)and a low-risk group(n=89),and the difference in survival time between the high-risk group and the low-risk group was statistically significant(P<0.001).Risk score was correlated with G stage,N stage and tumor residue(P<0.01).Single-cell analysis showed that the ex-pression of these genes was highest in tumor-associated macrophages(mean>0.5)and correlated with regulatory T cells and macrophage infiltration(P<0.05).Multivariate analysis showed that risk score was correlated with overall sur-vival after adjusting for clinical factors(P=0.0014).Conclusion:Based on three key immune-related genes(RIPK2,IRAK2 and CXCL11),we successfully constructed a model to accurately predict the prognosis of pancreatic cancer pa-tients,revealing the important role of these genes in the tumor immune microenvironment,and providing new insights and theoretical basis for pancreatic cancer prognosis assessment and immunotherapy research.

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
End Stage Liver Disease ; Follow-Up Studies ; Humans ; Liver Cirrhosis/drug therapy* ; Middle Aged ; Peripheral Blood Stem Cells ; Severity of Illness Index ; Treatment Outcome

In the era of artificial intelligence based on big data， data acquisition， storage and processing are more convenient， which provides a guarantee for accelerating the development of traditional Chinese medicine （TCM）， but it has not yet achieved organic integration with TCM theory. Based on preliminary research on the supramolecular "Qi chromatography" theory of TCM， combined with the current development trend of artificial intelligence， this paper analyzed the biological intelligence attribute of the function of TCM supramolecular "imprinting template"， in order to provide reference for the development of TCM drug innovation. Both the human body and Chinese materia medica are giant complex supramolecular bodies evolved from natural organisms. According to the "imprinting template"， the "social molecules" are controlled step by step to form the meridians and viscera. The interaction produces the original theory of TCM， in which the self-recognition， self-assembly， self-organization and self-replication of the "imprinting template" reflect the "intelligence" function attributes：the human body uses the "imprinting template" to self-identify and sense the ingredients of TCM， and store the memory information database in the meridian and collateral organs in the form of "imprinting template"， and then pass the "imprinting template". The comparison， analysis， and judgment of imprinting templates guide the self-assembly， self-organization and self-replication among "molecular society"， synthesize biological machines， produce biological functions， repair or strengthen biological supramolecular bodies， and present the most basic "intelligence" attribute. This suggests that the theory of theory-method-prescription-medicine of TCM is the weak embodiment of biological "intelligence"， while the human brain function is the strong embodiment of biological "intelligence". Since the intelligent function of supramolecular "imprinting template" runs through the natural world， artificial intelligence that can characterize the strong "intelligence" form of the human brain will also be integrated into all aspects of the natural world， suggesting the development direction of "intelligence" functionalization of drug innovation mode.

The application of modern scientific theories and technologies to explore the mechanism of Chinese medicine and its compounds is one of the key issues in realizing the modernization of traditional Chinese medicine （TCM） research. Chinese medicine and its compounds produce comprehensive pharmacodynamics through multiple components acting on multiple targets， the core of clarifying the mechanism is to solve the key scientific problems of static correlation and dynamic integration verification between the components and the target network topology. At present， the effective method to clarify the mechanism of Chinese medicine and its compounds is to statically correlate the topological network of in vitro components and targets through network pharmacology. Although there are also component-target verification studies， they often learn from research idea of single component-single target， it is urgent to establish a quantitative integration and overall verification method that conforms to the characteristics of TCM. According to supramolecular Qi chromatography theory of TCM， the microscopic mechanism of interaction between Chinese medicine and human body is actually the two supramolecular host and object groups （the active ingredient group of Chinese medicine and the target group of human body） based on imprinted template， which shows the macroscopic properties and pharmacodynamics. Based on this， the author proposes to use supramolecular Qi chromatography theory as the guidance， combined with supramolecular chemistry， network dynamics， quantitative pharmacology and other methods to quantitatively integrate and verify the compositions and the target groups with imprinted template as the core predicted by network pharmacology， looking for the optimal quality markers， greatly reducing the difficulty of multi-component-multi-target experimental verification of Chinese medicine and its compounds.

Objective:To construct the targeting evaluation method of traditional Chinese medicine （TCM） preparations based on supramolecular Qi chromatography theory， and to study the liver targeting effect of Bupleuri Radix on Pien Tze Huang. Method:The molecular connectivity index （MCI） was used to analyze the characteristics of imprinted template and liver targeting tendency of TCM mainly attributed to liver meridian and components of Pien Tze Huang， and combined with target dynamics and total statistical moment principle， aimed at the independent action characteristics of multi-component imprinted template of TCM， a method for evaluating the targeting of TCM preparations was established. Hepatoma rats in Pien Tze Huang group， Bupleuri Radix group， Pien Tze Huang+Bupleuri Radix group and blank group were tested and verified. Result:After the average value of MCI of TCM mainly attributed to liver meridian was deducted， the MCI similarity between Pien Tze Huang group and Bupleuri Radix group was 0.376 8， Pien Tze Huang+Bupleuri Radix group and Bupleuri Radix group was 0.988 2， so it was predicted that Bupleuri Radix could enhance the liver targeting of Pien Tze Huang. A system for evaluating the targeting of TCM compounds was established， including relative total uptake efficiency （RUE_T）， relative total concentration （RC_T）， relative imprinted tendency （RIT_T） and relative imprinted variance （RIV_T）. The RUE_T and RC_T of liver were the highest in all tissues （RUE_T=1.88>1，RC_T=2.30>1）， and the corresponding values of other tissues were all <1， indicating that Pien Tze Huang combined with Bupleuri Radix could increase its distribution in liver and enhance liver targeting. Except for plasma， the RIT_T and RIV_T of other tissues fluctuated around 1.0， indicating that targeted modification did not change imprinted tendency of Pien Tze Huang and had no significant effect on the types of components. Conclusion:Under the guidance of supramolecular Qi chromatography theory， a targeting evaluation parameter system can be established to characterize the multi-component imprinted effect of TCM preparations by MCI and total statistical moment parameters， so as to realize the evaluation of targeting of TCM preparations. The addition of Bupleuri Radix can increase the liver targeting of Pien Tze Huang.

Objective:The molecular connectivity index method and total statistical moment method were used to control the quality of traditional Chinese medicine （TCM）， and the stability and consistency of volatile components of Lonicerae Japonicae Flos and Lonicerae Flos were clarified. Method:Volatile oils in Lonicerae Japonicae Flos and Lonicerae Flos from different producing areas was extracted for GC-MS determination with electron bombardment ion source， ion source temperature of 230 ℃， and detection range of m/z 35-650. Then National Institute of Standards and Technology （NIST） 05 and ChemicalBook database were used for qualitative analysis of these volatile components， the peak area normalization method was used for quantitative analysis， and the total statistical moment parameters and the zero-order， first-order， second-order， third-order molecular connectivity indexes of the components were calculated. Result:Number of peaks （RSD were 28.5%， 33.4%， respectively）， total zero-order moments （RSD were 55.5%， 128.9%， respectively） and total second-order moments （RSD were 15.3%， 21.5%， respectively） of 10 batches of Lonicerae Japonicae Flos and Lonicerae Flos were unstable， indicating that the types and contents of volatile components fluctuated sharply， but the total first-order moments （RSD were 7.5%， 8.8%， respectively） and the zero-order， first-order， second-order and third-order molecular connectivity indexes （RSD ranged from 8.1% to 10.3% and 4.2% to 5.5%， respectively） were relatively stable， indicating that the overall "imprinting template" of the components was similar. Statistical analysis of each parameter found that there were no significant differences in the number of peaks， total first-order moments and zero-order， first-order， second-order， third-order molecular connectivity indexes between volatile oils from Lonicerae Japonicae Flos and Lonicerae Flos. Conclusion:Under the guidance of supramolecular gas evolution "imprinting template" theory， the molecular connectivity index method and total statistical moment parameters are used to jointly characterize the "imprinting template" of TCM components in vitro， which can control the stability and consistency of TCM quality.