Objective To investigate the effects of ropivavaine on gamma -aminobutyric acid(GABA)-activated membrane cur-rents in isolated dorsal root ganglion(DRG) neurons of the rats with ischiadic nerve chronic constriction injury (CCI) and to discuss the possible analgesia mechanism of ropivacaine .Methods The whole-cell patch clamp technique was used to record and compare the changes of GABA receptor activation currents of acute isolated DRG neurons after 30 s of ropivacaine preperfusion in the oper-ating side and the operative opposite side of the CCI model rats and the sham-operation group .Results (1)Compared with the oper-ative opposite side ,the sham-operation group and the control group ,the thermal withdrawal latency in the operative side group of the CCI model rats was notablely shortened(P<0 .05);(2)the amplitude of GABA-activated currents with different concentration GABA(0 .1-1 000μmol/L) in the operative opposite side group of the CCI operation was significantly greater than that of the op-erative side group and the sham-opeartion group ;(3)DRG neurons after ropivacaine preperfusion (0 .1-1 000μmol /L) showed va-rying degrees of enhancement effect on the 100 μmol/L GABA-activated currents ,the enhancement amplitude in the CCI operative opposite side group was significantly greater than that in the operative side group and the sham-operation group ;(4)The dose-re-sponse curve of DRG neurons GABA (0 .1-1 000μmol/L) activated current in the operative side group of the CCI rats after ropiva-caine pre-perfusion (100 μmol/L) was shifted to the left ,the difference between two EC50 had no statistical significance (P>0 .05) .Conclusion Ropivacaine has the enhancement effect on GABA activated currents in the DRG neurons of the CCI model rats , which could be one of reasons for ropivacaine producing the anesthetic and analgesic effect .

This investigation describes a new precise, sensitive and accurate stereoselective RP-HPLC method for determination of the enantiomers of a novel alpha- and beta-receptor blocking agent, 1-[4-(2-methoxyethyl) phenoxy]-3-[[2-(2- methoxyphenoxy) ethyl]amino]-2-propanol (TJ0711), in rat plasma. GITC was used for precolumn derivatization of TJ0711 enantiomers. Enantiomeric resolution was achieved on a Eurospher-100 C18 column (250 mmx4.6 mm ID, 5-mum particle size), with UV detection at 255 nm, and the mobile phase consisted of acetonitrile and water (58:42, v/v) containing 0.02% glacial acetic acid (v/v). Using the chromatographic conditions described, TJ0711 enantiomers were well resolved with mean retention time of 10.2 and 11.5 min, respectively. Linear response (r>0.999) was observed over the range of 0.125-12.5 mug/mL of TJ0711 hydrochloride enantiomers. The mean relative standard deviation (RSD%) of the results of within-day precision was [Symbol: see text] 10%. The proposed method was found to be suitable and accurate for the quantitative determination of TJ0711 enantiomers in rat plasma, and it can be used in pharmacokinetic studies.

Objective To investigate the effects of midazolam on GABAA receptor-activated currents in isolated dorsal root ganglion (DRG) neurons in rats.Methods Sprague-Dawley rats of both sexes,weighing 200-250 g,aged 4 weeks,were used in the study.The DRG neurons were isolated and GABAA receptor-activated currents were recorded using the whole-cell patch-clamp technique.GABAA receptor-activated currents were recorded after administration of the mixture of midazolam 3.00 μmol/L (final concentration)and the different final concentrations (0.03,0.10,1.00,10.00,100.00 and 1000.00 μmol/L) of GABA,after different concentrations of midazolam (0.03,0.10,1.00,3.00,10.00 and 100.00 μmol/L) was given,after administration of the mixture of different final concentrations(0.03,0.10,1.00,3.00,10.00 and 100.00 μmol/L) of midazolam and GABA 100.00 μmol/L (final concentration),and after administration of the mixture of midazolam 1.00μmol/L (final concentration) and GABA 100.00 μmol/L (final concentration)at the preset time points of perfusion with different concentrations of midazolam (0,20,40,60 and 120 s of perfusion).The enhancement rate of the currents was calculated.Results No change in the membrane currents was found after midazolam was perfused in the neurons sensitive to GABA.GABAA receptor-activated currents were enhanced after administration of the mixture of different concentrations of GABA and midazolam.GABAA receptor-activated currents were enhanced after different concentrations of midazolam were given compared with that before administration,and the enhancement rate of the GABAA receptoractivated currents was gradually increased with the increase in the concentration of midazolam and reached the peak at the concentration of 3.00 μmol/L.The enhancement rate of the GABAA receptor-activated currents was gradually increased with the prolongation of perfusion time and peaked at 40 s of perfusion.Conclusion Midazolam can enhance the GABAA receptor-activated currents in rat dorsal root ganglion neurons,indicating that midazolam increases the role of GABA through increasing the activity of GABAA receptors and has analgesic effect at the spinal cord level.

AIMTo explore the characteristics of the urinary excretion in the elderly patients and to offer some advice for the prevention and treatment of hyponatremia in the elderly patients.

METHODS42 inpatients aged over 80 were divided into tow groups according to their creatinine clearance rate (CCR). Meanwhile, 24 patients aged 45-59 and 31 patients aged 60-79 were chosen as the control groups. All patients were examined 24h urinary electrolytes and CCR.

RESULTS(1) The CCR in the elderly group was lower than in the middle-aged and old group and the 24 h urinary sodium excretion was accordingly diminished than the two groups. 24 h urinary sodium excretion in CCR abnormal group was also diminished than in CCR normal group. The urinary sodium excretion was not linearly correlate with the CCR in middle-aged group and old group but was linearly correlate in the elderly group. (2) The elderly patients' capability of holding blood sodium and excreting potassium was declined in the CCR normal group. But the urinary excretion of sodium, potassium and phosphonium were all diminished in CCR abnormal group. (3) All patients' sodium intake was higher than the criteria made by China Hypertension Association.

CONCLUSIONTheir urinary sodium excretion is linearly correlate with CCR. Urinary sodium excretion is increased when the elderly patients' renal function is relative normal but when the renal function is severely damaged, urinary sodium excretion is diminished.

Age Factors ; Aged ; Aged, 80 and over ; Calcium ; urine ; Coronary Disease ; urine ; Creatinine ; metabolism ; Humans ; Male ; Middle Aged ; Potassium ; urine ; Sodium ; urine

Objective To study the value of MR 3D FIESTA technology in spinal malformation. Materials and Methods 70 patients with spinal malformation and GE 1.5T superconducting MR machine got involved in. The scanning sequences included FSET2WI scanning at 2D axial position, coronal position and sagital positon, and FIESTA scanning at 3D coronal position and sagital position. Results FIESTA scanning could be used in the achievement of multi-slice and multi-angle coronal, sagital and axial images. Conclusion 3D MR FIESTA can be applied to rapid, multi-angle, multi-slice and continuous display of the spinal cord.

Objective:To express rationally engineered antibodies against EGFR and assess their affinity to EGFR and anti-tumor cell migration effect. Methods:L and V_H genes of humanized antibodies against EGFR were designed and synthesized. Genes encoding V_H and C_H were connected and then cloned into a pIRES based bicistronic expression vector. Gene encoding the corresponding L gene was also cloned into the same vector. 293T cells were transfected with the recombinant plasmid and the antibody expression was confirmed by Western blotting. The antibodies were purified by protein A based affinity chromatography. Binding of the humanized antibody to the EGFR was assessed by Surface Plasmon Renainance with Biacore3000, and the biological activity of the humanized antibody was determined by tumor cell invasion test.Results:Three expression vectors were constructed and the humanized anti-EGFR antibodies were expressed and purified successfully. In reducing SDS-PAGE, the antibodies exhibited two bands of approximately 25×10~3and 50×10~3, respectively. Western blot assay showed that the humanized antibodies had recognition specificity to goat-human IgG antiserum. Biacore assay revealed that the humanized antibody C3 binds to EGFR with high affinity(6.13×10~(-10)M). Cell migration test showed that C2,C3 and C5 could suppress growth and migration of tumor cells.Conclusion:Three anti-EGFR humanized antibodies (C2,C3 and C5) have been constructed and expressed successfully, and the C3 antibody retained high affinity for EGFR and showed improved inhibitory effect on tumor cell growth and migration.

Brain Stem/pathology* ; Death, Sudden/etiology* ; Fatal Outcome ; Humans ; Intracranial Hemorrhages/mortality* ; Leukemia/pathology*

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

This systematic review aimed to evaluate the efficacy and safety of assisted hatching (AH) performed in couples with advanced maternal age.We searched for randomized controlled trials (RCTs) in electronic databases,including MEDLINE,EMBASE and CENTRAL (from inception to January 2018);in addition,we hand-searched the reference lists of included studies and similar reviews.We included RCTs comparing AH versus no treatment (control).The meta-analysis was performed by RevMan 5.3 software.The search retrieved 943 records and 8 RCTs were included,comprising 870 cycles (n=440 for AH,and n=430 for control).There was no significant difference in the rates of live birth (RR 0.88,95％ CI 0.65 to 1.18,3 RCTs,n=427,I2=0％),clinical pregnancy (RR 1.00,95％ CI 0.83 to 1.19,8 RCTs,n=870,I2=22％),implantation (RR 1.07,95％ CI 0.83 to 1.39,4 RCTs,n=1359,I2=0％),miscarriage (RR 1.13,95％ CI 0.66 to 1.94,2 RCTs,n=116,I2=0％) and multiple pregnancy (RR 0.89,95％ CI 0.31 to 2.52,1 RCT,n=97,I2=not applicable) between the treatment group and control group.No reasonable conclusions could be drawn regarding reproductive outcomes after AH in patients with advanced maternal age due to the small sample pooled in meta-analyses.Studies of high methodological quality and with adequate power are necessary to further investigate the value of AH in assisted conception of those patients.

Traditional Chinese ancient prescriptions have been used for treatment of liver cancer for a long history and the scientific and rational compatibility is a great wealth for modern research and development (R&D) of new drugs. The research and development of new drugs are often accompanied with a large investment, a long cycle and a high risk, especially for the anti-tumor drugs R&D which are facing more risks and lower successful rate. In this research, the regularity of compatibility of drugs was analyzed from 124 anti-hepatoma ancient prescriptions by computer program. The results can offer help to the R&D of anti-hepatoma new drugs and reduce the risk of drug screening. In addition, we surveyed 22 companies in this field from six provinces such as Beijing, Shanghai, Tianjin and so on and obtained 240 risk assessment questionaires. Then we used qualitative analysis method to interpret the greatest impacts for the risks in the process of R&D, production and sales of anti-hepatoma new drugs. The study provides a basis for anti-liver cancer drugs R&D researchers, who can take effective measures to reduce the R&D risks and improve successful rate.
Carcinoma, Hepatocellular ; drug therapy ; history ; China ; Drug Discovery ; history ; Drug Incompatibility ; Drug Prescriptions ; history ; Drugs, Chinese Herbal ; history ; therapeutic use ; History, Ancient ; Humans ; Liver Neoplasms ; drug therapy ; history ; Research ; history