Traditional Chinese medicines (TCM) is one of the most important sources of new drugs.The rapid development of modern science and technology has brought new opportunities for TCM.Admittedly,new academic theory is getting into a golden period of innovation.Key technologies that enbody TCM features and adapt to modern drug-screening requirements are urgently needed.After five years' endeavor,the authors' group has made great progress in the new theories and methodologies for the discovery of bioactive compounds from TCM.In this review,a total of five key technologies:library-bioactivity-structure integration,biological and chemical fishing technology,ligand-and receptor-based virtual screening,profile-bioactivity relationship and the technology for discovering bioactive equivalent combinatorial components (BECCs),were introduced.In the text,several valuable demonstrations over the TCM-based drug discovery were provided,for uncovering the scientific basis of TCM and accelerating the process of TCM modernization.

BACKGROUND:Studies have shown that tibial plateau posterolateral fractures can be treated by posterolateral knee approach, however, there is no clear anatomical research to deeply evaluate and analyze this approach. OBJECTIVE:To evaluate the efficacy and safety of posterolateral knee inverted“L”shaped pathway in invloving tibial plateau posterolateral fractures. METHODS:Eight fresh frozen adult corpses, 16 knees side, were al dissected using posterolateral inverted“L”shaped pathway. During the dissection, the exposure range was observed and important parameters of anatomical structure were measured. RESULTS AND CONCLUSION:The pathway may be ful y exposed to the posterolateral aspect of tibial plateau and posterior cruciate ligament tibial insertions. The operations completed by out team did not create any obvious interference to superior tibiofibular joint, fibular head and posterolateral corner structure. The exposed mean length of common peroneal nerve in incision was 56.48 mm, with a mean angle of 14.7° tilt towards the axis of the fibula. The mean distance between the neck of the fibular and fibular head tip was 31.26 mm, an average of 42.18 mm to the joint line. The mean distance between the opening of the interosseous membrane and the articular surface was 48.78 mm. The divergence of the fibular artery from the posterior tibial artery was an average of 76.46 mm from articular surface. These results confirm that posterolateral inverted“L”shaped pathway met the requirements of anatomical reduction and buttress fixation for posterolateral tibial plateau fracture. Exposure of the common peroneal nerve can be minimized or even avoided by modifying the skin incision. Because the popliteal artery branches anterior tibial artery passed through interosseous membrane hole and peroneal artery and then separated from the posterior tibial artery, pathways dissection to distal deep area should be carried out careful y. Placement of a posterior buttressing plate carries a high vascular risk if the plate is implanted beneath these vessels.

Objective To study the effect of metformin on the growth of megakaryocytic leukemia cell line Dami and to explore the molecular mechanisms of the inhibitory effect of metformin on the proliferation of Dami. Methods The Dami cells were cultured and divided into control and 1,2,4,8,16 and 32 mmol·L-1 metformin groups.Then MTT test was performed to detect the inhitory rate of proliferation of Dami cells after treated with different concentrations of metformin. Flow cytometry was used to examine the distribution of cell cycle, and Western blotting was carried out to analyze the expressions of Cdc2 and CylinB1 and the phosphorylation of Cdc2. Results The MTT results showed that compared with control group,the inhibitory rates of proliferation of the Dami cells in 32 mmol·L-1 metformin groups at 0,24,48,72 and 96 h (35.1%±2.3%,49.7%±5.1%, 78.85±0.9%,79.1%± 3.0%%,and 85.2%± 3.2%)were significantly increased(P<0.01),Furthermore, after metformin treatment for 72 h,the inhibitory rates of proliferation of the Dami cells in 1,2,4,8,16 and 32 mmol·L-1 metformin groups were (33.8 ± 0.3)%,(51.9 ± 0.2)%,(59.4 ± 1.6)%,(65.5 ± 2.0)%, (75.5±0.9)%,and (79.1±3.0)%,respectively. Metformin inhibited the growth of Dami cells in a time-and dose-dependent manner. The flow cytometry results results revealed that compared with control group, the percentages of Dami cells in G2/M phase in 1,2 and 4 mmol·L-1 metformin groups were increased from (26.0± 0.5)% to (38.5 ± 1.5 )%, (48.4 ± 1.1 )%, and (58.2 ± 2.7 )%;there was significant difference in the percentages of Dami cells in G2/M phase between control group and 4 mmol·L-1 metformin group (P<0.01). Western blotting analysis showed that compared with control group, the expressions of Cdc2 and CyclinB were evidently reduced, the phosophorylation of Cdc2 at Tyr1 5 was up-regulated, and the phosphorylation at Thr1 6 1 was down-regulated.Conclusion Metformin can inhibit the growth of Dami cells and induce G2/M arrest,and its mechanism may be related to inhibiting the activation of Cdc2/CyclinB1 complex.

Objective To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs ) on vascular endothelial growth factor ( VEGF ) and monocyte chemoattractant protein-1 ( MCP-1 ) of acute myocardial ischemia-reperfusion (AMI-R) injury in rats. Methods 24 Sprague-Dawley rats were randomly divided into sham group, AMI-R group and UCMSCs treatment groups on average. The rats were sacrificed on the 10th day after UCMSCs transplantation, and the myocardial tissues below the ligature were taken. The mRNA and protein expressions of MCP-1 of the tissue were detected by RT-PCR and Western Blot respectively, and the expression of VEGF protein was detected by immunohistochemistry. Results The relative expression levels of MCP-1 mRNA and the protein in UCMSCs group were significantly lower than those in sham group and AMI-R group (all P<0.05). The expression of VEGF protein in UCMSCs group was significantly higher than that in sham group and AMI-R group, the differences were statistically significant(all P<0.05). Conclusion UCMSCs transplantation can promote the angiogenesis and decrease the inflammation reaction in the treatment of acute myocardial ischemia-reperfusion injury.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.