Malignant tumors are a major disease threatening human health with disability and mortality rates increasing yearly.Protein tyrosine phosphatase 2(SHP2)of Src homology 2,an important member of the protein tyrosine phosphatase family,has a wide range of functions,and its expression is elevated in a wide range of solid tumors.SHP2 plays an important regulatory role in invasion,metastasis,proliferation,apoptosis,and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but no systematic studies have reported on the role of SHP2 in digestive system tumors.Here,we reviewed the biological functions and clinical significance of SHP2 in seven tumor types of the digestive system,explored its roles and mechanisms in cancer development stages,and summarized the development of SHP2 inhibitors to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance to improvement the cancer patient survival rate.

Objective:To analyze the relationship between gait speed or grip strength and all-cause mortality in elderly inpatients over 75 years old, and to compare their predictive value for all-cause mortality.Methods:A prospective cohort study was conducted and enrolled elderly patients aged ≥75 years hospitalized from December 2016 to December 2019 at the Department of Integrated Medicine and Geriatrics, Fuxing Hospital, Capital Medical University.Gait speed(m/s)and grip strength(kg)were respectively measured via the 6-meter walk test and a dynamometer.The patients were followed up for more than 1 year after discharge, and the time of all-cause mortality was recorded.The Cox regression model was used to analyze the correlation between gait speed, grip strength or their combination and the risk of all-cause mortality.ROC curves were statistically analyzed using the DeLong test.Results:A total of 704 patients were enrolled, with an average age of(83.8±6.3)years; the median follow-up time was 33(24, 42)months.During the follow-up period, all-cause death occurred in 131 cases(18.6%).Compared with the high gait speed and high grip strength groups, the low gait speed and low grip strength groups had higher all-cause mortality(all P<0.05).The Cox regression model was used to analyze the relationships between gait speed, grip strength and all-cause mortality.The results showed that gait speed( HR=2.255, 95% CI: 1.462-3.477, P<0.001)and grip strength( HR=1.815, 95% CI: 1.232-2.673, P<0.001)were associated with the risk of all-cause mortality after adjustment for other factors; When gait speed slowed down and grip strength decreased, the risk of death reached the highest level( HR=3.156, 95% CI: 1.829-5.445, P<0.001).The AUC of the gait speed model(0.703, 95% CI: 0.667-0.736)was higher than the AUC of the grip strength model(0.648, 95% CI: 0.611-0.683), with a difference of 0.055(95% CI: 0.006-0.103, P=0.026). Conclusions:Decreased gait speed or grip strength is related to an increase of death risk.The risk of death is highest when the patient has both slowed gait speed and decreased grip strength.The predictive value of gait speed for death is better than grip strength.Together they can be used as simple, rapid and effective tools to predict all-cause mortality in this population.

Objective:To investigate the correlation between acoustic radiation force impulse imaging(ARFI) and reserve function of liver and the feasibility of liver reserve function assessment by ARFI.Methods:According to the inclusion criteria, 74 patients were screened and 71 patients were finally enrolled from Henan Province People′s Hospital during June 2017 and June 2019. The portal vein diameter (D PV), spleen length (L SP) were measured by two-dimensional ultrasound. The liver shear wave velocity (LSWV) and spleen shear wave velocity (SSWV) were measured by ARFI. Serological markers were checked, and the indocyanine green (ICG)15-minute retention rate (ICG R15) was measured by excretion test. The patients were divided into ICG R15<10% group and ICG R15≥10% group, the difference of the measurements between two groups were calculated, the correlations of the measurements and ICG R15 were analyzed. LSWV diagnostic performance for liver reserve function was evaluated by the ROC curve. Results:There were significant differences in LSWV, D PV, SSWV, L SP, aspartate transaminase(AST), alkaline phosphatase(ALP), y-glutamyl transpeptidase(γ-GGT) and albumin (ALB) between ICG R15<10% group and ICG≥10% group( P<0.05), but no significant differences in other measurements( P>0.05). The correlations between ICG R15 and LSWV( r=0.673, P<0.001), D PV( r=0.355, P<0.05), SSWV( r=0.384, P<0.05), L SP( r=0.403, P<0.001), ALP( r s=0.245, P<0.05) and ALB( r s=-0.390, P<0.05) were statistically significant. The ROC curve showed high diagnostic performance for liver reserve function assessment by LSWV. The area under the ROC curve was 0.903 (95% CI=0.810-0.961, P<0.01), and the cut-off value was 2.15 m/s (sensitivity 84.6%, specificity 86.7%). Conclusions:The LSWV can evaluate the reserve function and it is a useful supplement to the ICG excretion experiment.

Objective:To observe the effect of Er Chen Tang on CYP2E1 and mitochondrial energy metabolism in nonalcoholic fat-ty liver disease ( NAFLD) to explore the role of Pinellinae Rhizoma Praeparata ( PRP) and Citri reticulatae pericarpium ( CRP) in the treatment of nonalcoholic fatty liver disease. Methods:Er ChenTang and the prescription without PRP or CRP was respectively given the animal models by gastric gavage. The serum levels of ALT, AST, triglyceride, cholesterol, SOD and MDA in hepatic tissue, and the contents of liver tissue CYP2E1 and ATP were detected in the mice. Results:The CYP2E1 levels in NAFLD mice increased signif-icantly with abnormal mitochondrial energy metabolism. Compared with those in the model group, the levels of ALT, AST, triglyceride and cholesterol were significantly reduced by Er Chen Tang, meanwhile, the content of CYP2E1 was reduced and also restored liver en-ergy metabolism. The treatment effect significantly decreased when the lack of PRP or CRP, and the ability of restoring liver mitochon-drial energy metabolism of Er Chen Tang decreased significantly when the lack of PRP (P<0. 05). After the removal of CRP, the in-hibition ability of Er Chen Tang to CYP2E1 levels significantly decreased (P<0. 05). Conclusion:Er Chen Tang can effectively im-prove nonalcoholic fatty liver diseases, and effectively reduce the content of CYP2E1 in liver tissue of mice and restore the mitochondri-al energy metabolism.

Objective To investigate the clinical efficacy of Xinmailong on heart failure in coronary heart disease and on the levels of hs-C-reactive protein (hs-CRP)and N-terminal B-type natriuretic peptide (NT-proBNP).Methods 84 elderly patients diagnosed with heart failure in coronary heart disease were enrolled in this study at our hospital from October 2014 to October 2015.All patients were randomly divided into the control group with conventional treatment(n=42) and observation group with conventional plus Xinmailong treatment(n =42).The Lee's heart failure score,cardiac function grade,quality of life score and the changes of plasma hs-CRP and NT-proBNP after one week of therapy were compared between the two groups before versus after treatment.The adverse reactions were observed during the treatment.Results The clinical efficacy rate of heart failure after treatment was significantly higher in the observation group (83.3％,35 cases)than in control group(54.7 ％,23 cases) (x2 =8.016,P =0.033).The clinical efficacy of heart function after treatment was significantly higher in the observation group(80.9 ％,34 cases)than in the control group (59.5 ％,25 cases) (x2 =6.219,P =0.019).After treatment,the quality of life score was significantly lower in observation group (15.89 ± 3.39) than in the control group (23.80 ± 5.66) (t =7.266,P =0.026).The plasma levels of NT-proBNP and hs-CRP were significantly lower after than before treatment in NT-proBNP[(1 136.6±236.8)ng/L and (2 266.9±260.9)ng/L],and in hs-CRP[(3.06 ±0.26)mg/L and (3.56±0.29)mg/L] (t=6.608、5.106,P=0.019、0.009).There were no serious adverse reactions in both groups during the treatment.Conclusions Xinmailong can not only improve safely and effectively the quality of life of patients,but also block the atherosclerosis of the inflammatory response.

Objective: To investigate the protective effects of matrine combined with glycyrrhizic acid on chronic liver injury induced by carbon tetrachloride, and explore the protective mechanism from the points of energy metabolism and CYP enzyme.Methods: The chronic hepatic injury model of rats was induced by CCl4.The changes of activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were measured to observe the protective effect of the two drugs and their combination.The contents of glutamate dehydrogenase (GLDH) in serum and adenine nucleoside three phosphate (ATP), adenosine diphosphate (ADP) and adenine monophosphate (AMP) in liver tissue were determined to evaluate the regulation effect on hepatic energy metabolism and mitochondrial function.The levels of CYP1A2, CYP2E1 mRNA and protein in liver tissue were detected by real-time PCR and Western Blot to evaluate the two drugs and their combination on the regulation function of liver CYP enzyme.Results: Matrine (72.8 mg×kg-1)and glycyrrhizic acid(43.4 mg·kg-1)could decrease the serum activities of ALT and ALT in chronic hepatic injury model, and the combination (matrine 36.4 mg·kg-1+glycyrrhizic acid 21.7 mg·kg-1) had the most significant protective effect (P＜0.05).Matrine (72.8 mg·kg-1)and glycyrrhizic acid(43.4 mg·kg-1)could decrease GLDH in serum,and restore the content of ATP in liver (P＜0.05).Matrine (72.8 mg·kg-1) had no effect on the expression of CYP1A2 and CYP2E1mRNA, and glycyrrhizin (43.4 mg·kg-1) could inhibit the expression of CYP1A2, CYP2E1mRNA and protein (P＜0.05).Conclusion: Matrine combined with glycyrrhizin has obvious regulation effect on mitochondrial function and liver protective effect in chronic hepatic injury model.

Objective:To establish a TLC identification method for three medicinal ingredients and a GC method for the content determination of metnthol in Baihua Dingchuan tablets. Methods:Citrus Reticulata, Ephedra Sinica and Schisandra Chinensis were i-dentified by TLC. GC was used to determine the content of menthol in Baihua Dingchuan tablets. The chromatographic conditions were as follows:a DM-5 capillary column(30 m × 0. 53 mm, 1. 5 μm) was adopted. The injection port temperature was 200℃. An FID was used as the detector and the temperature was 300℃. The temperature program was as follows:the initial column temperature was 80℃, and then rose to 120℃ at the rate of 8 ℃· min-1 , finally rose to 185 ℃ at the rate of 15 ℃· min-1 and maintained for 10 min. The carrier gas was nitrogen and the flow rate was 3. 0 ml·min-1 . The sample size was 1 μl. Split injection was performed with the diversion ratio of 1 :5. Results: The three traditional Chinese medicines could be identified by TLC. The content of menthol showed a good linear relationship within the range of 1. 484-74. 200μg · ml-1 ( r =0. 9998 ) by GC. The average recovery was 97. 76% RSD=0 . 58%(n=9). Conclusion:The methods are specific and simple with good reproducibility. They can be used for the quality control of Baihua Dingchuan tablets.

Objective:To establish a TLC identification method for three medicinal ingredients and a GC method for the content determination of metnthol in Baihua Dingchuan tablets. Methods:Citrus Reticulata, Ephedra Sinica and Schisandra Chinensis were i-dentified by TLC. GC was used to determine the content of menthol in Baihua Dingchuan tablets. The chromatographic conditions were as follows:a DM-5 capillary column(30 m × 0. 53 mm, 1. 5 μm) was adopted. The injection port temperature was 200℃. An FID was used as the detector and the temperature was 300℃. The temperature program was as follows:the initial column temperature was 80℃, and then rose to 120℃ at the rate of 8 ℃· min-1 , finally rose to 185 ℃ at the rate of 15 ℃· min-1 and maintained for 10 min. The carrier gas was nitrogen and the flow rate was 3. 0 ml·min-1 . The sample size was 1 μl. Split injection was performed with the diversion ratio of 1 :5. Results: The three traditional Chinese medicines could be identified by TLC. The content of menthol showed a good linear relationship within the range of 1. 484-74. 200μg · ml-1 ( r =0. 9998 ) by GC. The average recovery was 97. 76% RSD=0 . 58%(n=9). Conclusion:The methods are specific and simple with good reproducibility. They can be used for the quality control of Baihua Dingchuan tablets.

OBJECTIVE:To prepare Xuangui zhitong dispersible tablets and optimize its formulation technology. METHODS:Using disintegration time as index,single factor test was conducted for filler,disintegrating agent,the types and amount of adhe-sives and compression pressure. The amount of mixed disintegrating agent,avicel and gum arabic were optimized by orthogonal test. The tablet quality by optimized formulation was detected,and disintegration time,the content and dissolution rate of tetrahy-dropalmatine were determined;the similarity of in vitro dissolution rate of dispersible tablets and dropping pills were evaluated by similarity factor test. RESULTS:The optimized formulation was composed of 25% MCC as fillers,9% PVPP and 9% L-HPC as mixed disintegrants,85% ethanol solution as adhesives,micro-silica gel 2%,compression pressure of 3.0 kg/cm2. The average dis-integration time was 1.22 min,and the content of tetrahydropalmatine was 1.097 mg/g. The accumulative dissolution rate was more than 80% at 10 min and more than 90% at 15 min. The similarity factor f2 of dissolution curve was 62,using dropping pills as ref-erence preparation. CONCLUSIONS:Xuangui zhitong dispersible tablet had a rapid disintegration and the behavior of dissolution is similar to Xuangui zhitong dropping pills.

Objective The purpose of this study is to construct eukaryotic gene vector of herpes simplex virus type 1 thymidine kinase(HSV1-tk)and to observe the expression of HSV1-tk in lung adenocarcinoma AGZY cell line.Methods The full length HSV1-tk gene was amplified by PCR from plasmid pHSV 106 and was inserted into pMD18-T.The recombinant plasmid was recombined with eukaryotic vector plRES 2-EGFP u-sing gene recombinant technique .HSV1 -tk was transfected into adenocarcinoma AGZY cell line with Lipo-fectamineTM 2 000.Fluorescence microscopy was used to detect the transfection and expression of HSV 1-tk.RT-PCR was used to detect the mRNA levels of HSV 1-tk.The cell proliferation was measured by MTT assay .Re-sults A length of 1 130 bp gene sequence was obtained by PCR .The expressions of HSV 1-tk at mRNA and protein levels were displayed by RT -PCR and Western blot .MTT analysis showed that there were no significant changes cell survival on after transfection .Conclusion The eukaryotic expression vector of HSV 1 -tk report gene is successfully constructed and HSV 1-tk is effectively expressed in transfected AGZY cells .