1.Clinical study of artificial dermis combined with autologous thin skin graft for repairing soft tissue wounds at joints
Chongqing Medicine 2014;(28):3727-3729
Objective To investigate the efficacy and prognosis of artificial dermis combined with autologous skin graft in the body joints dermal wounds.Methods Twenty-five cases were collected from 2008 to 2013,who used artificial dermis combined with autologous skin graft repair articular wounds,including 10 cases of wound knee,5 cases of the ankle,4 cases of the elbow,2 cases of the wrist,3 cases of the knuckles,1 case of the axillary.Skin graft survival after surgery,the extent and functional recovery of scar formation after 3 months were observed.Results Among the patients,who underwent artificial dermis combined with autologous skin graft repair operations,dermal tissue of 1 8 cases formed well by timely removal of pus after phase one surgery.Three cases suffered artificial dermis infection,and the dermal tissue formed again after the clean dressing and drainage of pus.Two cases with severe infection underwent surgical debridement and replacement of artificial dermis,and the same treatment effect was achieved. After skin graft of phase two,autologous skin lives well.Wound area of 2 cases is small,with striping of artificial dermis film,the wound covered by the surrounding normal epithelium,and healed themselves.It shows good recovery of function in patients after 3 months follow-up,and no formation of obvious scar and scar contracture.Conclusion Artificial dermis combined with autologous skin graft therapy can not only improve the survival rates of autologous skin graft,but reduces the degree of scar contracture of joints and the long-term function recovery,and it provides an effective treatment program for tissue wounds.
2.Rapid simultaneous determination of ten major flavonoids in Tetrastigma hemsleyanum by UPLC-MS/MS.
Wen XU ; Zhiqin FU ; Jing LIN ; Xuecheng HUANG ; Hongmin YU ; Zehao HUANG ; Shiming FAN
Acta Pharmaceutica Sinica 2014;49(12):1711-7
In this study, a rapid and sensitive analytical method was developed for the determination of 10 major compounds (procyanidin B1, catechin, procyanidin B2, rutin, isoquercitrin, kaempferol-3-O-rutinoside, astragalin, quercitrin, quercetin, and kaempferol) in Tetrastigma hemsleyanum by using ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-MS/MS) in multiple-reaction monitoring (MRM) mode. UPLC-MS/MS assay with negative ion mode was performed on a Waters CORTECS C18 (2.1 mm x 100 mm, 1.6 μm) with the mobile phase consisting of acetonitrile (A) and 0.1% aqueous formic acid (B) in gradient elution at a flow rate of 0.25 mL · min(-1) and the column temperature was set at 45 °C. Under the optimized chromatographic conditions, good separation for 10 target compounds were obtained including chiral isomer procyanidins B1 and B2 were completely separated within 8.5 min. Satisfactory linearity was achieved with wide linear range and fine determination coefficient (r > 0.996 6), the overall recoveries were ranged from 95.44%-110.40% with the RSD ranging from 2.37%-8.69%. It is the first report about simultaneous analysis of 10 major flavonoids components in Tetrastigma hemsleyanum by using UPLC-MS/MS method, which affords highly sensitive, specific, speedy and efficient method for quality control of Tetrastigma hemsleyanum
3.Artificial intelligence-based drug development: current progress and future challenges
Zehao YU ; Leiming ZHANG ; Mengna ZHANG ; Zhiqi DAI ; Chengbin PENG ; Siming ZHENG
Journal of China Pharmaceutical University 2023;54(3):282-293
In recent years, artificial intelligence (AI) has been widely applied in the field of drug discovery and development.In particular, natural language processing technology has been significantly improved after the emergence of the pre-training model.On this basis, the introduction of graph neural network has also made drug development more accurate and efficient.In order to help drug developers more systematically and comprehensively understand the application of artificial intelligence in drug discovery, this article introduces cutting-edge algorithms in AI, and elaborates on the various applications of AI in drug development, including drug small molecule design, virtual screening, drug repurposing, and drug property prediction, finally discusses the opportunities and challenges of AI in future drug development.
4.Analysis of transcriptome sequencing and related genes of flavonoid biosynthesis from Anoectochilus roxburghii
Fuxian ZOU ; Wen XU ; Zehao HUANG ; Xun ZHANG ; Shuyun CHEN ; Yu LIN ; Wei XU
Journal of China Pharmaceutical University 2019;50(1):66-74
Transcriptome sequencing was performed for the first time on Anoectochilus roxburghii(AR)in different harvesting periods using RNA-seq high-throughput sequencing technique, and the results were verified and analyzed by Q-PCR and HPLC. A total of 51, 370 genes were obtained by transcriptome sequencing and annotated to the database of Nr, GO, Swiss-Prot, KEGG and KOG. The species that were sequenced according to the homology sequence were the same as AR monocotyledon plants. Through comparison of AR transcriptome in different periods, it was found that the differences were mainly in flavonoid biosynthesis-related genes. The expression levels of flavonoid biosynthesis-related genes(trans-cinnamate 4-monooxygenase, caffeoyl-CoA O-methyltransferase, chalcone synthase, flavonol synthase, shikimate O-hydroxycinnamoyltransferase and flavonoid 3′, 5′-hydroxylase)were verified by Q-PCR, and the results were consistent with those of transcriptome sequencing. The contents of 6 flavonoids(rutin, isoquercitrin, narcissin, quercetin, kaempferol and isorhamnrtin)were determined by HPLC. The results showed that the expression of flavonoid synthetic gene in AR increased with the growth time, and the variation trend of flavonoid compound content and gene expression were basically consistent. Combined with transcriptome data, the biosynthetic pathway of flavonoid content in AR was plotted. This study provides important genetic resources for the key genes of flavonoid synthesis in AR and the biosynthesis of flavonoids, as well as the basis for the development of its medicinal value.
5.Research and application progress of organoids in liver cancer
Zehao LIU ; Chenxuan ZHANG ; Keshuai DONG ; Jia YU
Chinese Journal of Hepatobiliary Surgery 2023;29(12):945-949
Primary liver cancer is a major global public health issue and currently the second leading cause of cancer death worldwide. The continuous changes in early cancer detection and treatment strategies have improved the overall survival rate of patients. Emerging organoid technologies have had a dramatic impact on cancer research in recent years, and tumor organoids are widely used in basic and translational cancer research. Tumor organoid culture technology will bridge the gap among molecular genetics, biology and clinical treatment. In this review, we discussed the recent different applications of liver organoids in liver cancer biology and clinical translation, involving liver cancer molecular studies, microenvironment and metastasis studies and drug screening trials, in order to provide a reference for clinical practice.
6.Growth Inhibitory and Pro-Apoptotic Effects of Hirsuteine in Chronic Myeloid Leukemia Cells through Targeting Sphingosine Kinase 1
Shan GAO ; Tingting GUO ; Shuyu LUO ; Yan ZHANG ; Zehao REN ; Xiaona LANG ; Gaoyong HU ; Duo ZUO ; Wenqing JIA ; Dexin KONG ; Haiyang YU ; Yuling QIU
Biomolecules & Therapeutics 2022;30(6):553-561
Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.
7.Optimization and purification of extraction of polysaccharides from Anoecto-chilus roxburghii
Songbai ZHANG ; Xun ZHANG ; Wen XU ; Wei XU ; Zehao HUANG ; Yu LIN ; Shuyun CHEN
Journal of Pharmaceutical Practice 2020;38(4):354-358
Objective To optimize the process of ultrasonic extraction of polysaccharide in Anoectochilus roxburghii and to investigate the method of protein removal. Methods The extraction rate of polysaccharide was used as the detection index. On the basis of single factor investigation, Box-Behnken experimental design and response surface method were used to optimize the three factors of material-liquid ratio, ultrasonic time and ultrasonic extraction temperature. The five deproteinization methods including Sevage reagent method, TCA method, salt method (NaOH-CaCl2 and NaOH-NaCl) and hydrochloric acid method were investigated with the retention rate of polysaccharide and protein removal rate. Results The optimal extraction conditions of polysaccharide from Anoectochilus roxburghii were as follows: liquid-to-solid ratio was 10∶1, extraction temperature was 48 ℃ and extraction time was 36 min with extraction 2 times, ultrasonic power was 300 W, the extraction rate was 13.13%. NaOH-CaCl2 deproteinized methods∶ the loss rate of polysaccharide was 18.74%, and the removal rate of protein was 95.62%. Conclusion Ultrasonic extraction is easy to operate, and the optimized extraction method can achieve a high extraction rate. NaOH-CaCl2 deproteinization methods can get high protein removal rate and polysaccharide retention rate. This method is suitable for the research and development of the active components of the polysaccharides from Anoectochilus roxburghii.