Triple-negative breast cancer (TNBC) is a subtype of breast cancer known for the poor prognosis due to its strong invasiveness, high recurrence rate, and lack of effective treatment. Therefore, there is an urgent need to find targeted therapy for TNBC. Cathepsin A (CTSA) is an acidic serine carboxypeptidase that is highly expressed in various tumor tissues. However, the role and molecular mechanism of CTSA in TNBC are still unclear. This study found that the expression of CTSA was upregulated, and the high expression of CTSA was positively correlated with the poor prognosis of TNBC. The results further showed that knocking down CTSA inhibited the proliferation, invasion, and colony formation of TNBC cells, improved drug sensitivity of cells, and inhibited the progression of TNBC. Mechanistically, CTSA inhibited the ubiquitination and degradation of the promyelocytic leukemia protein (PML) protein by blocking the interaction between PML and its E3 ubiquitin ligase RNF4, thus maintaining the stability of PML nuclear bodies (PML-NBs). The inhibitor of CTSA had a positive therapeutic effect on inhibiting the characteristics of TNBC stem cells. In conclusion, this study demonstrates that inhibiting CTSA to decrease the stability of PML protein may be a promising therapeutic strategy for TNBC. All animal experiments in this experiment were approved by the Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College (approval number: IMB-20240326D502).

Objective To make an attempt at some conditions on extracting heavy metals in chry-soidine by supercritical CO_2 extration.Methods Taking sodium diethyldithiocarbamate trihydrate(NaDDC?3H_2O) as chelating agent and ethanol as entrainer,the orthogonal test was designed and ICP-MS used to mensurate the contents of Cu,As,and Pb in chrysoidine under different conditions.According to the results,the factors including extracting pressure,temperature,chelating agent dosage,and time were studied.Results When the test sample was 10 g,the optimum condition was that extracting pressure: 25 MPa,the temperature : 60 ℃,chelating agent dosage: 2 g,extracting time: 3 h,and the ethanol dosage: 10 mL.After extracting reaction,the contents of heavy metal in chrysoidine reached United States FDA standard.Conclusion The contents of heavy metal in Chinese herb medicine are notably decreased,and this way provides a new thought and research technique to decrease the contents of heavy metal.

Objective To explore the relationship between early changes of central venous-toarterial carbon dioxide difference (Pcv-aCO2) and the prognostic in patients with septic shock.Methods One hundred and three patients with septic shock were retrospectively analyzed.The patients were divided into death group (37 cases) and survival group (66 cases) according to prognosis.The patients were divided into four groups according to the changes of 0 and 6 h Pcv-aCO2:Pcv-aCO2 persistently high group (16 cases),Pcv-aCO2 increased group (19 cases),Pcv-aCO2 decreased group (22 cases),Pcv-aCO2 persistently normal group (46 cases).All the patients were treated with early goal-directed therapy (EGDT),and central venous oxygen saturation (ScvO2) ≥0.70 was the target.The acute physiology and chronic health evaluation (APACHE) Ⅲ score,sepsis related organ failure assessment (SOFA) and mortality were compared.Results There was no statistical difference in 0 h Pcv-aCO2 (P ＞ 0.05).The Pcv-aCO2 in 6,12 and 24 h in survival group was significantly lower than that in death group [(5.0 ± 1.8) mmHg (1 mmHg =0.133 kPa) vs.(6.8 ± 2.3) mmHg,(4.7 ± 2.3) mmHg vs.(7.2 ± 3.0) mmHg,(3.2 ± 1.5) mmHg vs.(7.5 ± 3.3) mmHg],and there was statistical difference (P ＜ 0.05 or ＜ 0.01).The APACHE Ⅲ score in survival group was significantly lower than that in death group [(51.6 ± 23.8) scores vs.(87.7 ± 35.9) scores],and there was statistical difference (P ＜ 0.05).The time of mechanical ventilation,APACHE Ⅲ score,SOFA,length of stay in hospital and mortality in Pcv-aCO2 persistently high group and Pcv-aCO2 increased group were significantly higher than those in Pcv-aCO2 decreased group and Pcv-aCO2 persistently normal group,and there were statistical differences (P ＜ 0.05 or ＜ 0.01).Conclusion The Pcv-aCO2 persistently high during the early resuscitation of septic shock is associated with multi-organ dysfunction and worse prognosis,and provides guidance for clinical treatment.

A method was developed for determining residual dexamethasone and betamethasone in swine liver by HPLC-MS/MS with isotope dilution. The samples were digested by β-glucuronidase/aryl sulfatase, and extracted) with acetonitrile. Further cleanup was performed on C_(18)) cartridge and liquid-liquid extraction with sodium) carbonate solution. Then the supernatant was dried under nitrogen and residues were dissolved in mobile) phase. The samples were analyzed by HPLC-MS/MS on a Hypercarb C_(18)) column with a mixture of acetonitrile-water-formic acid as the mobile phase. The samples were quantified with the internal standard calibration curve method using isotope dilution. The limit of detection for dexamethasone and betamethasone in swine liver was 0.12 μg/kg and 0.14 μg/kg, respectively. The limits of quantification were 0.42 μg/kg and0.47 μg/kg), respectively. The average recoveries were 97.3%-111.0%, the intra-assay relative standard deviations were 1.85%-5.65% and the inter-assay relative standard deviations were 2.8%-8.0% at spiked levels of 0.75-2.00 μg/kg. There was a good linear correlation (the correlation coefficient is above 0.9997) between the ratio of peak areas of quantitative ion-pair to internal standard and concentration of analyte) in the range of 10-500 μg/L.

Objective To compare the effectiveness of supraclavicular brachial plexus block guided by ultrasound with that guided by nerve stimulator or anatomical landmarks. Methods One hundred and twenty ASA Ⅰ-Ⅲ patients (81 male, 39 female) aged 16-62 yrs weighing 40-75 kg scheduled for upper extremity operation under brachial plexus block via supraclavicular approach were randomized into 3 groups ( n = 40 each) : In group U block was guided by ultrasound; in group N nerve stimulator was used to locate the brachial plexus and in group T block was performed in the traditional way based on anatomical landmarks. A mixture of equal volumes of 0.75% ropivacaine and 2% lidocaine (0.4 ml?kg-1) was injected in the 3 groups. The onset and intensity of sensory block of musculocutaneous, median, radial and ulnar nerves were measured and analgesia was rated as excellent, effective and failure.Results The rate of satisfactory block of ulnar nerve was significantly lower than that of musculocutaneous and radial nerves in group N and T ( P

Objective To study effect of pentanuclear copper complexes of imino acetic acid two aromatic derivatives on oxidative cutting DNA. Methods Synthesized complexes later, protonation constants and the stability constants of the complexes were determined by potentiometric titration method, the cutting DNA was studied by agarose gelelectrophoresis.Results Under physiological conditions, complexes H4L1, H4L2, between H6L3 and Cu2 +coordination capability was stronger; three carboxylic multi copper complexes in Cu2 + concentration cutting efficiency were higher than the corresponding mononuclear copper complexes, synergistic effect exists between Cu2 + Center; H6L3 complexes of the three DNA cut the highest efficiency, complex H4L1 was followed, complex H4L2 cutting efficiency was the lowest.Conclusion Change the complex chelating ligands has great influence on the properties of complex, which provides a theoretical basis for the design and synthesis of copper nucleases reasonable.

Aerosol and splatter formed during dental procedure were collected pre and post rinsing with Xipayi mouth rinse or 1% H2O2,cultured 48 hours with blood agar plates,counted the bacterial colonies.Both groups were effective in reducing bacterial aerosols(P 0.05).Bacterial aerosols by dental procedure can be reduced by using mouthwash pre-operationally,both Xipayi mouth rinse and 1% H2O2 are effective mouthwashes.

BACKGROUND:Relative to blood samples, mouth swab samples are more beneficial for apolipoprotein E gene polymorphism analysis among large cohorts. However, agreement has not yet been reached about how to extract genomic DNA form mouth swab samples.
OBJECTIVE:To develop an appropriate method to extract genomic DNA form mouth swab samples, which are suitable for apolipoprotein E gene polymorphism analysis.
METHODS:Fifty mouth swab samples from patients with sporadic Alzheimer’s disease were col ected. Magnetic nanoparticles and PicoDNA trace nucleic acid extraction kit were used to extract genomic DNA form mouth swab samples. And the purity and concentration of the genomic DNA extracted by the two methods were analyzed. Then PCR amplifications and DNA electrophoresis were performed to confirm whether the genomic DNA was able to amplify desired DNA fragments. DNA sequencing was applied to analyze apolipoprotein E gene polymorphisms.
RESULTS AND CONCLUSION:Genomic DNA extracted by the two methods was of high purity. The concentration of genomic DNA extracted by magnetic nanoparticles was higher than by PicoDNA trace nucleic acid extraction kit, and the difference had statistical significance (P<0.05). Al the genomic DNA were able to performed PCR amplifications to obtain desired PCR products, but results of DNA electrophoresis showed that DNA fragments were more clear by nanoparticles method. The results of DNA sequencing were the same by the two methods. The distribution ofε2,ε3,ε4 genotypes of apolipoprotein E gene was 6%, 71%, 23%, respectively. Magnetic nanoparticles were better than PicoDNA trace nucleic acid extraction kit for extracting genomic DNA form mouth swab samples for apolipoprotein E gene polymorphism analysis.

Objective To analyze the detection rate of neonatal congenital malformation,and to explore the risk factors for neonatal malformation.Methods A total of 29 831 infants born in Shenzhen People's Hospital from January 2011 to December 2015 were analyzed retrospectively,the detection rate of congenital malformations was calculated,381 infants with congenital malformation were selected as malformation group,and 381 healthy infants were selected as healthy control group,and the risk factors of congenital malformation were analyzed.Results A total of 381 infants with congenital malformation were screened out,the incidence rate of congenital malformation being was 12.77‰(381/ 29 831 cases).The incidence rates of multi-finger or multi-toe,cleft lip,congenital heart disease were the high,which were 18.64％ (71/381 cases),17.32％ (66/381 cases) and 16.80％ (64/381 cases),respectively.The multiple Logistic analysis showed that birth children with low weight newborns (＜ 2 500 g),multiple births,preterm birth (＜ 37 weeks),pregnancies ＞ 1,low literacy levels of mothers,living in towns,late childbirth (≥ 35 years of age),pregnancy syndrome,viral infection during early pregnancy,medication history during pregnancy,rubella unvaccinated,exposure to harmful substance,smoking and alcohol during pregnancy and paternal smoking,chronic diseases,total 16 items were related risk factors for neonatal congenital malformations (all P ＜ 0.05).Among them,the impact of viral infection during early pregnancy,alcohol,smoking,pregnancy syndrome,exposure to harmful substance,medication history during pregnancy on the incidence of malformations in neonates was relatively serious.Conclusions The incidence rate of congenital malformations among neonates conforms to the present situations in China,which was closely correlated with genetic and environmental factors.Health education targeting pregnant women and the women of childbearing age should be carried cut to reduce the birth of neonatal congenital malformations.

Objective To observe the effects of Zhennao-Ning capsule on cerebral microcirculation.Methods Cerebral hypoperfusion model of mices was induced by right common carotid arteries ligation method,The cerebral blood flow for 5min was recorded under normal circumstances comand for 30min when modeled,and then calculate the rate of blood flow changes.Microcirculatory impairment model of rats was induced by intravenous injection of high molecular dextran(HMD).The time of the emergence of microcirculatory impairment was recorded.Vascular flow,blood flow pattern and the number of outlets in the same range were recorded.Results The blood flow was significant decrease in the cerebral hypoperfusion model mice,when compared with the control mice.Zhennao-Ning capsules at the dosage of 1500 mg/kg、750 mg/kg treatment could improve the cerebral blood flow of rats at 10,20,and 30 min after modeled (56％,51％,50％ and 42％,49％,51％,respectively,P＜0.01).Zhennao-Ning capsules at the dosage of 600 mg/kg,300 mg/kg could significantly reduce the change of blood flow pattern(P＜0.01),improve vascular flow rate (26％,36％,P＜0.05 or P＜0.01),extend the time of the emergence in the microcirculatory impairment model rat (53％,34％,P＜0.01).Conclusion Zhcnnao-Ning capsules could improve microcirculatory impairment and partly cure the clinical migraine disease.