CDKs proteins are a kind of cell cycle protein-dependent kinases, which serve as important roles in controlling cell division and transcriptional stages. Among them, CDK9, as a key regulator responsible for the transcriptional elongation of cells, drives the development of various malignant cells and is considered as an important target in the field of anti-tumor drug development. However, the CDK family proteins feature high conservativeness and similarity in structure, leading to the poor selectivity and severe side effects for traditional small-molecular CDK9 inhibitors, which has limited their clinical applications. In view of this, there is an urgent need to investigate CDK9 targets through a novel strategy. The PROTAC is an emerging drug discovery strategy that the degrader could specifically recognize the target protein through indirect linkage with ubiquitin ligases and ultimately eliminate the target protein through the ubiquitination degradation system. This paper provides a brief overview of the structure and function of CDK9 protein, its relationship with the poor prognosis of clinical diseases, as well as the currently reported small molecular inhibitors. The latest research progress on the targeted degradation of CDK9 protein based on PROTAC technology is highlighted. Finally, the development prospects of this target protein in this novel technology field are summarized and prospected, aiming to provide a reference for the development of antitumor drugs in this direction.

This article systematically introduced the development of Smart Healthcare mode in Hangzhou. From the aspects of connotation, pattern, characteristics and the change of medical treatment mode, the authors pointed out that the development of Smart Healthcare must follow such principles as satisfaction of the people, enhanced inter-departmental synergy, government-guided social participation, and full involvement of medical workers.

Objective:To investigate the relationship between serum microRNA-222(miR-222) and metabolism of glucose and lipid in women with polycystic ovary syndrome(PCOS).Methods:A total of 100 patients with PCOS (PCOS group) were enrolled from July 2018 to July 2020 in Puren Hospital Affiliated of Wuhan University of Science and Technology, and another 85 sterility patients were selected as control group. The levels of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein (LDL-C), fasting insulin (FINS), fasting plasma glucose (FPG), insulin resistance index (HOMA-IR) as well as serum miR-222 were compared between two groups, and the correlation between serum miR-222 and metabolism of glucose and lipid was analyzed.Results:The levels of TC, TG, LDL-C, FPG, FINS, HOMA-IR, miR-222 in PCOS group were higher than those in the control group: (1.30 ± 0.25) mmol/L vs. (1.04 ± 0.21) mmol/L, (4.36 ± 0.91) mmol/L vs. (3.67 ± 0.61) mmol/L, (2.51 ± 0.89) mmol/L vs. (2.13 ± 0.42) mmol/L, (5.34 ± 1.56) mmol/L vs. (4.91 ± 0.84) mmol/L, (11.08 ± 3.83) mU/L vs. (7.49 ± 2.53) mU/L; the level of HDL-C in PCOS group was lower than that in the control group: (1.08 ± 0.47) mmol/L vs. (1.53 ± 0.50) mmol/L, and the differences were statistically significant ( P<0.05). The results from Logistic regression analysis showed that the levels of TC, TG, HDL-C, LDL-C, FINS, HOMA-IR, miR-222 were independent risk factors for abnormal of metabolism of glucose and lipid of polycystic ovary syndrome patients ( P<0.05). The correlation analysis showed that miR-222 expression had positive correlation with TC, TG, LDL-C, FINS, HOMA-IR ( r = 0.760, 0.737, 0.769, 0.749, 0.825, P<0.05), and had negative correlation with HDL-C( r = -0.743, P<0.05). Conclusions:The serum miR-222 shows abnormal increase in the PCOS patients, and is closely related to glucose and lipid metabolism. It can be used as a biomarker of abnormal glucose and lipid metabolism.

Objective To establish a method of reverse hybridization to detect five subfamilies of low risk Human Papillomaviruses(HPV6,11,42,43 and 44)and eighteen subfamilies of high risk HPV (HPV16,18,31,33,35,39,45,51,52,53,56,58,59,66,68,73,83 and MM4)in one reaction.Methods Special probes for twenty-three HPV subfamilies were fixed on nylon membrane bars,biotin labeled general primers mediated polymerase chain reaction(GP-PCR)were applied in HPV DNA amplification.PCR amplified DNA fragments were reversely hybridized with special probes that were fixed on the membranes. All samples(136)detected by reverse hybridization method were paralleled with the methods of Hybridization Capture Ⅱ(HC-Ⅱ)and sequencing.Results Positive rate of the 136 samples detected by reverse hybridization was 41.9%,while HC-Ⅱ 42.6% and sequencing 40.4%.Reverse hybridization detection indicated coherence with the other two methods(Kappa 0.8644 and 0.9089,respectively).While sequencing was lab standard for DNA test,the sensitivity was 96.36%,specificity was 95.06%,accuracy was 95.59%.Conclusions Method of reverse hybridization is adaptable to 23 kinds of HPV subfamilies, which can confirm the exactly subfamilies of HPV infection.This method is adaptable in clinical detection of HPV,with high sensitivity,high specificity,simply and convenient operation and the results are easily to be read.

Objective To summarize and discuss the diagnostic and treating experiences of chronic pancreatitis with mass in the head. Methods Eight patients of chronic pancreatitis with mass in the head who were misdiagnosised as carcinoma of head of pancreas were analyzed retrospectively in the past 10 years. Results All the patients exhibited abdominal pain,5 of whom were with jaundice and 3 with anorexia. All the patients were misdiagnosised as carcinoma of head of pancreas before the operation,but the pathology after operation indicated chronic pancreatitis. The pancreaticoduodenectomy was performed in 5 patients,the choledochojejunostomy in 2 patients,while the exploratory laparotomy in 1 patient. After the operations,the abdominal pain was relieved in 7 patients, while 2 patients who accepted pancreatoduodenectomy suffered from pancreatic fistula,1 of whom died in the end. Conclusion It’s hard to differentiate the chronic pancreatitis with mass in the head from the carcinoma of head of pancreas before operation. If the carcinoma of head of pancreas can’t be excluded during the operation,the pancreatoduodenectomy should be performed,while the duodenum-preserving total resection of the head of the pancreas or any intra-drainage operations should be done if chronic inflammation is found in the whole pancreas with a negative result of the biopsy of the pancreas through the needle aspiration.

Objective To evaluate the relationship between vascular endothelial function of coronary heart disease and the severity of coronary artery disease(CHD).Methods 73 patients undergoing coronary angiography were divided into two groups:CHD group(n=39)and non-CHD group(n=34)according to the result of coronary angiography.13 healthy subjects without risk factor of CHD were chosen as normal control group.FMD and NTG-MD of endothelial-dependent and independent dilatation of brachial artery were measured by using of high frequency linear-array uhrasonography for assessment of the vascular endothelial function.and the relationship between the vascular endothelial function and the severity of coronary artery stenosis was analyzed.Results A significant difference was obtained in the FMD among the CHD group,non-CHD group and control group[(4.81±2.33)%vs.(9.29±3.88)%vs.(13.58±1.80)%,F=48.012,P＜0.01).Significant difference was shown in NTG.MD among the three groups[(13.72±3.27)%vs.(15.64±2.65)%vs.(16.54±2.98)%,F=6.015,P＜0.01]and significant difference was shown between CHD group and the other two group(P＜0.05).The FMD was negatively correlated with the basdine value of the brachial artery.tlle number of stenotic coronary ateries and the severity of coronary artery stenosis(r=-0.224,-0,316,-0.721,P=0.038,0.003 and ＜0.001).NTG-MD was also negatively correlated with the baseline value of the brachial artery,the number of stenotic coronary arteries and the severity of coronary artery stenosis(r=-0.483,-0.258,-0.372,P＜0.001,0.027,0.001).Stepwise regression analysis displayed a linear relationship between FMD and the severity of coronary artery stenosis,the baseline value of the brachial artery(r=-0.012,-0.022,P＜0.001).NTG-MD was linearly related to the baseline value ofthe brachial artery and the severity of coronary artery stenosis(r=-0.032,-0.0073,P＜0.001).Conclusion The degree of damage of endothelial function of coronary heart disease is linearly correlated with severity of coronary arteIT stenosis.

AIM: To determine the contents of ephedrine、laetrile、glycyrrhizic acid and liquiritin in Huagai Powder traditional decoction and granule decoction(Herba Ephedrae,Semen Armeniacae Amarum,Radix et Rhizoma Glycyrrhizae,etc.) by HPLC. METHODS: An Agilent SB-C_(18) column was used for ephedrine,the mobile phase was acetonitrile-0.1% phosphoric acid(4∶96),detection wavelength at 207 nm;An Agilent XDB-C_(18) column was used for laetrile,the mobile phase was methanol-water(23∶77),detection wavelength at 215 nm;An Agilent XDB-C_(18) column was used for glycyrrhizic acid,the mobile phase was methanol-0.2 mol/L ammonium-acid(67∶33∶1),detection wavelength at 250 nm; An Agilent XDB-C_(18) column was used for liquiritin,the mobile phase was acetonitrile-0.5% acetic acid(20∶80),detection wavelength at 276 nm. RESULTS: There were discrepancies between traditional decoction and granules in the contents of four ingredients,the average contents in granules were more than those in the traditional decoction. CONCLUSION: The peaks of the four ingredients are(segregated)(effectively),and the method is simple,conveient,exact and has good reproducibility,the other ingredients do not have interferences for the determination.

Objective To investigate the value of remifentanil IV PCA joint doula in labor analgesia.Methods 480 single fetus at term vaginal delivery of maternal patients were randomly divided into four groups:120 cases voluntary implementation of remifentanil IV PCA joint doula maternity paternity were selected as the experimental group; 120 cases in control group an order to carry out the studies in our hospital childbirth select one to one Doula paternity maternal; 120 cases voluntary implementation of the control group 2 intravenous analgesia with remifentanil maternal;120 cases in control group three normal deliveries in our hospital does not take any measures of maternal.The analgesic effect,labor time,postpartum hemorrhage,cesarean section rate,neonatal asphyxia,the medical staff satisfaction were compared in four groups.Results Analgesic effect of experimental group and control group 2 was significantly better than the control group 1 and the control group 3,the differences were statistically significant (t =4.34,4.76,4.94,5.32,6.32 ;4.42,4.71,4.86,5.28,6.26,all P ＜ 0.05).The first,second,third labor stage of experimental group were (516 + 123)min,(29 + 10)min,(8 + 4)min,which were shorter than those of the other groups (t =3.76,4.21,4.18,all P ＜ 0.05).Conclusion Remifentanil IV PCA joint Doula is safe and easy for labor analgesia.

Objective: To construct and identify a lentiviral vector harboring RNAi sequence targeting the human high mobility group A1(HMGA1) gene.Methods: The effective sequence of siRNA targeting the HMGA1 gene confirmed in our previous study,the complementary DNA containing both sense and antisense Oligo DNA of the targeting sequence was designed,synthesized and cloned into the pGCL-GFP vector diced by the restriction enzyme of HpaⅠ and XhoⅠ,which contained the U6 promoter and green fluorescent protein(GFP).The resulting lentiviral vector containing HMGA1 shRNA was named LV-sh HMGA1 and confirmed by PCR and DNA sequencing.A total of 293T cells were cotransfected with LV-sh HMGA1,pHelper 1.0 and pHelper 2.0.All the virus stocks were produced by Lipofectamine2000-mediated transfection.The titer of the virus was tested according to the expression level of GFP.Results: PCR analysis and DNA sequencing demonstrated that the RNAi sequence targeting the human HMGA1 gene was successfully inserted into the lentiviral vector.The titer of the recombinant lentiviral vector was 5?107 TU/ml.Conclusion: The successful construction of the lentiviral vector of HMGA1 has prepared the ground for further studies on the functions of the HMGA1 gene with the RNAi technique.

BACKGROUND: Two-dimensional electrophoresis (2-DE) is precise and effective for the isolation and analysis of complex protein mixtures, has become one of valuable key techniques for proteome. Mice models were as research subjects to model human disease status, one of important methods for cardiovascular disease. The establishment and optimization of 2-DE for proteomes of mice myocardium will provide basis for heart disease.OBJECTIVE: To establish and optimize a stable technique of 2-DE for proteomic analysis of mice myocardium.DESIGN: Mice were used as research subjects, observational comparative study.SETTING: Department of Pathology, Nanfang Hospital Affiliated to Southern Medical University.PARTICIPANTS: The experiment was performed at the Department of Pathology, Nanfang Hospital Affiliated to Southern Medical University between February and September 2004. Totally 12 male BABL/c mice of 4-5 weeks without special-pathogen free with the body mass of 12-15 g were selected, which was provided by the Experimental Animal Center of Southern Medical University.METHODS: The mice were put to death by dislocation of cervical vertebra under drugged state to obtain heart. Various protein extraction method,loading sampling buffer, strip range of IPG, sampling volume of protein,staining method and so on were compared, analyzed, scanned and digilized,and then performing image analysis. Each link in the study was established and optimized.MAIN OUTCOME MEASURES: Resolution of protein and reproducibility of the trial.RESULTS: A method that was optimal for cardiac tissue can isolate about a total of 910 protein spots on pH 4-7 gel strips. 200 μg was fit for silver stain while 1000 μg was for Coomassie stains. It was found that in the myocardium of normal mice about (920±30) protein spots were obtained in 17 em pH 3-10 L gel strip, while around (880±30) were gained in the pH 4-7 L gel strip. The mean matching rate achieves to 86. 9%.CONCLUSION: The findings of the trial showed that 2-DE technique can be effectively applied for proteomics of myocardium of mice to regulate and optimize, and relatively stable separation method of myocardial protein was established.