Cadmium ; pharmacology ; Cells, Cultured ; Heat-Shock Proteins ; biosynthesis ; Humans ; Metallothionein ; biosynthesis ; Ubiquitin ; biosynthesis

Cadmium ; adverse effects ; Dose-Response Relationship, Drug ; Environmental Exposure ; adverse effects ; Humans ; Occupational Exposure ; adverse effects ; Risk Assessment

Detection of serum tumor markers in clinical application is simple,which has become an in dispensable means in clinical medical work,and played an important role in the early detection of malignant tumor,benign and malignant tumor differential diagnosis,guiding the stage and predicting prognosis.But because of its sensitivity and specificity have limitations,we should find more new markers.

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.

Hand Disinfection ; Health Personnel ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal

Antigens, CD ; immunology ; Antigens, Differentiation, Myelomonocytic ; immunology ; Child, Preschool ; Diagnosis, Differential ; Histiocytes ; immunology ; pathology ; Histiocytosis, Sinus ; diagnosis ; pathology ; Humans ; Lymph Nodes ; immunology ; pathology ; Lymphatic Diseases ; diagnosis ; pathology ; Male

OBJECTIVE:To investigate the characteristics of adverse drug reactions(ADR) in our hospital so as to promote rational clinical drug use.METHODS:244 ADR cases collected in 2005 in our hospital were analyzed retrospectively.RESUL TS:Among the 244 cases,the female exceeded the male;79.83% of the patients were more than 40 years old.The cardiovascular system medicines took the lead which amounted to 45.69% of the total,then came the antimicrobial medicines.The intravenous administration caused most of ADRs.Alprostadil Injection accounted for 9.02% of the total, the highest.Skin and its appendages impairment cases took the biggest percentage at 28.14%.CONCLUSION:we should pay more attention to the ADR monitoring and the spread of ADR knowledge and enhance the ADR awareness of medical staff.sen or avoid the occurrence of ADR,monitoring of which and publicizing of ADR knowledge should be emphasized.

Objective To explore the roles and possible mechanism of calcium-sensing receptor(CaSR) in cell cardiac hypertrophy model using angiotensin Ⅱ (Ang Ⅱ ).Methods The cultured neonatal rat ventricular myocytes were treated with Ang Ⅱ as cell cardiac hypertrophy model.Hypertrophic neonatal rat cardiomyocytes were treated with GdCl3(a specific agonist of CaSR) and/or with Ro318220(a specific inhibitor of PKC pathway).To evaluate the status of cardiac hypertrophy,cell diameter was observed by HE dyeing,and protein content was determined through coomassie brilliant blue protein kit.The intracellular calcium concentration( [ Ca2+]i) was determined by laser scanning confocal microscope.The protein expression of CaSR and PKC pathway were analyzed using Western blotting.Results ①Compared to the control group(0.1263 ± 0.0443),the protein expression of CaSR was increased in Ang Ⅱ group and in GdCl3 group(0.1963 ± 0.0375,0.2778 ± 0.0564,all P＜ 0.05).Moreover,compared with Ang Ⅱ alone,the increase was significant in GdCl3 group(P ＜ 0.05).②Compared to control group(222.70 ± 22.09),AngⅡ group(392.16 ± 36.85) remarkably increased [Ca2+]i(P＜ 0.05),and this increase of [Ca2+]i was further enhanced in GdCl3 group (502.60 ± 44.21) versus Ang Ⅱ group (P ＜ 0.05).③Compared to control group,Ang Ⅱ could induce cardiomyocyte hypertrophy,and GdCl3 enhanced the effect.Moreover,this enhancement was attenuated by Ro318220.④Compared to control group(0.27 ± 0.07,0.69 ± 0.06,0.87 ± 0.04),the protein expression of PKCα,PKCε and PKCδ was increased in Ang Ⅱ group(0.60 ± 0.16,1.02 ± 0.13,1.20 ± 0.18,all P＜ 0.05) and the protein expression of PKCα,PKCε was increased in GdCl3 group(0.82 ± 0.16,1.34 ± 0.12,all P ＜ 0.05).Moreover,compared with Ang Ⅱ group,the protein expression of PKCα,PKCε was obviously increased in GdCl3 group (all P ＜ 0.05);compared with GdCl3 group,the protein expression of PKCα,PKCε(0.41 ± 0.10,0.85 ± 0.14) was obviously decreased in Ro318220 group(all P ＜ 0.05).Conclusions CaSR is involved in cardiac hypertrophy induced by Ang Ⅱ through PKC pathway in cultured neonatal rat cardiomyocytes.

Objective To evaluate the value of a CT ribs unfolding algorithm in the diagnosis of rib fracture. Methods Retrospective analysis of 180 patients who suffered chest trauma to do the chest or/and abdominal CT examination, and they also had the surgical or CT referral information. The images of these patients were postprocessed by software(Bone Reading software)and hand-drawn method(multi-point hand-painted CPR method). The rib fracture was observed and the time of reading was record. The diagnosis of fractures was confirmed by follow-up review or surgery. The fractures diagnosis sensitivity of the two post-treatment methods were measured, and the McNemar test was used to compare the difference between the software method and the hand-drawn method. Results Eight patients were excluded due to program failure, 172 cases were included in the study. Of the 172 patients, 63 patients suffered 259 fractures(178 ribs). The sensitivity of the software group was 91.7％(475/518), which was higher than that of the hand-painted group(86.3％, 447/518), the difference was statistically significant(P=0.005). The time of reading were (30.3 ± 3.3)and(173.2 ± 4.5)s, respectively, and the difference had statistically significant(P=0.001). Conclusion Compared to the traditional CPR method, the bone reading technique was used in patients with rib fractures during thoracic CT postprocessing can shorten the reading time and increase the sensitivity of the diagnosis.

OBJECTIVETo study the molecular mechanism of curcumin in human esophageal carcinoma cell line (EC109).

METHODSEC109 cells were cultivated in vitro. When 80%-90% confluence was reached, they were treated with curcumin in different concentrations (15-120 µmol/L). The effects on cell proliferation were examined by CCK-8 colorimetry. The ultrastructure of EC109 cells were detected with transmission electron microscope(TEM). The cells apoptosis was observed with laser confocal microscope(LCM) by AnnexinV-FITC/PI double staining. The proteins level of PTEN, AKT, GSK3β and Caspase 3 were tested by flow cytometry(FCM) .

RESULTSCCK-8 test showed that curcumin could inhibit the proliferation of EC109 cells in a time- and concentration-dependent manner. TEM and LCM examinations indicated that curcumin could make EC109 cells apoptosis. The data of FCM showed that curcumin could increase the expression of PTEN, GSK3β and Caspase 3, decreased the expression of AKT.

CONCLUSIONThe effects of curcumin on inhibiting proliferation and promoting apoptosis of EC109 cells were related with increased expression of PTEN and inhibition of PI3K/AKT signaling pathway.

Apoptosis ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Curcumin ; pharmacology ; Esophageal Neoplasms ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; PTEN Phosphohydrolase ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction