An on-line solid phase extraction-high performance liquid chromatography ( SPE-HPLC ) system was applied in the plasma pharmacokinetic study of highly active anti-cancer compound tyrosine kinase inhibitors (TEB-415) in mouse. The on-line SPE-HPLC method associated with Ultimate3000 system which was applied to the determination of the blood drug level of TEB-415 in mouse plasma. C18 column ( Venusil MP, 150 mm × 4. 6 mm, 5μm) was used as analytical column and the mobile phase consisted of acetonitrile-5 mmol/L monopotassium phosphate buffer ( pH 3 . 5 ) at a flow rate of 1 . 0 mL/min was used as the isocratic elution. An MF Ph-1 column (10 mm×4 mm, 5 μm) was used as on-line SPE column, and water and water-acetonitrile were used as the washing solvent and elution solvent respectively. The detection wavelength was set at 262 nm. The pharmacokinetic parameters were calculated by WinNonlin 5. 2 software. The linear range of the calibration curve was between 100 and 20000 μg/L, and the limit of qualification was 20 μg/L. The extraction recovery was between 90 . 5% and 94 . 6%. The RSD of intra-day and inter-day precision was less than 3. 5%. The accuracy of short-term stability, freeze-thaw stability and long-term stability were between 91. 49% and 101. 96%. After oral medication, the mean peak time (Tmax) of TEB-415 in mice was 5. 29 h, and the mean maximum concentration ( Cmax) was 3403μg/L. The area under the curve ( AUC) of TEB-415 was 24600 μg/L·h. This drug's mean half-life was 3. 84 h, and its mean retention time (MRT) was 6. 56 h. These parameters suggested that TEB-415 had appropriate rate of absorption and elimination with preferable bioavailability.

Background Keratectasia after laser in situ keratomileusis (LASIK) is a rare but severe complication,which threatens the visual acuity and corneal strength.Corneal collagen crosslinking (CXL) is a new therapy that increases the security and decreases the risk of complication.However,the effectiveness and safety of LASIK-CXL is still need to be concerned.Objective This study was to evaluate the safety of LASIK-CXL for myopia and astigmatism with thin cornea.Methods A prospective cohort study was designed.A total of 128 eyes of 64 patients with thin corneal and myopic astigmatism enrolled in Beijing Tongren Eye Center from January 2014 to January 2015.The patients were assigned to LASIK group (74 eyes of 37 patients) and LASIK-CXL group (54 eyes of 27 patients).Refractive surgery was performed by Visumax femtosecond lasrer and VISX S4 excimer laser.Eyes of LASIK-CXL group applied accelerated CXL immediately after LASIK.The follow-up was 6 months.Manifest refraction,uncorrected (UDVA) and corrected distance visual acuity (CDVA),average keratometry values (AveK),anterior segment OCT (AS-OCT),corneal hysteresis (CH) and corneal resistance factor (CRF) were examined before and after operation.This research passed through Ethics Committee of Beijing Tongren Hospital.Results The spherical equivalent (SE) of the LASIK group and LASIK-CXL group were (-6.49 ±2.41)D and (-6.97 ±2.41) D before operation and decreased to (-0.68 ±0.88) D and (-0.75 ±0.94) D 6 months after operation.The UDVA (LogMAR) was 1.18±0.28 and 1.05±0.38 before operation and elevated to-0.06±0.09 and-0.03±0.186 months after operation in the LASIK group and LASIK-CXL group.The preoperative AveK values were (44.37 ±1.46) D and (44.47± 1.50)D in the LASIK group and LASIK-CXL group and reduced to postoperative (39.30±2.06) D and (38.66± 1.80) D.The preoperative SRI of LASIK group and LASIK-CXL group were 0.25 ±0.21 and 0.24±0.22,which increased to 0.29±0.24 and 0.28±0.24.The SAI values were 0.36±0.16 and 0.39±0.15 before operation,which increased to 0.57 ±0.31 and 0.75 ±0.376 months after operation,and the SAI value of the LASIK-CXL group was significantly higher than that of LASIK (F =10.220,P--0.002).CRF values of LASIK and LASIK-CXL were (8.44±1.44)mmHg and (8.63±1.35) mmHg in preoperation,which decreased to (5.74±1.31) mmHg and (6.25± 1.24) mmHg in postoperation.The result of LASIK-CXL was higher than that of LASIK (F=8.650,P =0.040).CH values were 8.78 ± 1.51 and 8.69 ± 1.62 in preoperation,which decreased to (7.23 ± 1.08) mmHg and (6.50±1.32)mmHg.The value of LASIK-CXL was lower than that of LASIK (F =5.860,P =0.017).The mean depth of demarcation line was (228.45±28.24) μm (range 165 to 310 μm) on OCT,which was presented in 45 eyes (81.82％) at 1 month in postoperation.Conclusions Accelerated CXL with FS-LASIK is effective and safe in improving visual acuity in myopic astigmatism patients with thin cornea,which also can increase the rigidity of the cornea.

Objective To assess the value of CMV viral load test in the diagnosis and prognostic judgment of infantile cytomegalovirus infection with whole blood and urine specimens. Methods 50 infants with active CMV infection were selected, which pp65 antigen was positive in serological detection and either CMV-IgM positive or the titer of CMV-IgG ≥40. The viral load in whole blood and urine specimens was detected before and after a course of preemptive ganciclovir treatment and the pp65 antigen was determined after treatment. Results 98% patients were manifested as cytomegalovirus viral load quantitative measurement in whole blood positive before the treatment, while 14% after. The positive ratio of pp65 assay after therapy was 6%. And there was no significant difference between the results of the two kinds of detection methods measurement in urine before and after treatment was 98% and 90%, respectively. The results of urinary viral load quantitative detection did not coincide with clinical characteristics of CMV infection (P＜0.05,Sp＝0.11,PVP＝0.55, (Youden's index)＝0.09). Conclusions Good coincidence could be found between CMV-DNA quantitative measurement in whole blood and pp65 antigenemia assay. And the former could be used as a diagnostic index of CMV positive infection. While single urinary viral load quantitative detection had no significance for the distinction between active and latent CMV infection and dynamic monitoring of CMV treatment.

Objective To compare the effects of preload with intravenous infusion of 6％ hydroxyethyl starch combined with phenylephrine or dopamine to prevent the hypotension after combined epiduralspinal anesthesia in parturient undergoing caesarean section.Methods Eighty patients with ASA class Ⅰ or Ⅱ[,were randomly divided into Dopamine group and Phenylephrine group,40 cases in each group.The 6％hydroxyethyl starch 500 ml was infused at the tate of 20 ml/(kg · h) after the intravenous catheterization was established and after the finishing of the infusion of 250 ml,the dopamine 5 mg (Dopamine group) or 200 ug phenylephrine (Phenylephrine group) were added respectively in residual liquid.After the bupivacaine was injected into the subarachnoid space,the intravenous infusion was continued at the same rate until the fetus was taken out and the blood pressure and heart rate were measured at intervals of 1 min.The blood sample of fetal cord was taken to measure ther troponin Ⅰ concentration.Results The incidence of hypotension after combined epidural-spinal anesthesia anesthesia in dopamine group (2/40) and in phenylephrine group (3/40) was with no statistical difference (P ＞ 0.05) ;The incidence of bradycardia in dopamine group (0/40) was significantly lower than that in phenylephrine group (6/40)) (P ＜0.05) ; The incidence of tachycardia in dopamine group (8/40) was significantly higher than that in phenylephrine group (1/40) (P ＜0.05) ; The troponin Ⅰ concentration of fetal cord blood in dopamine group [(0.21 ±0.07) ng/ml] and in phenylephrine group [(0.18 ±0.09)ng/ml]was with no statistical difference (P ＞0.05).Conclusion Preload with intravenous infusion of 6％ hydroxyethyl starch combined with phenylephrine or dopamine can effectively prevent the hypotension after combined epidural-spinal anesthesia in parturient undergoing caesarean section with no significant effect on the fetus and both can be chosen in terms of the heart rate of parturient before anesthesia.

To explore how to create and optimize a promotion index system of medical quality evaluation, this article focuses on the hospital visiting process from patients, using analyzing collected those index system from couples of Grade Ⅲ hospitals in Beijing, and combining the results of literal study, field study and specialist consult, according to the different situation of general hospitals and specially hospitals, with the spirit of "maintaining the patients benefits, safeguarding the patients safety,and enhancing the medical quality", introduces the framework of the promotion index system, the rules to select the indicator, and so on, and discusses several problerns related to creating the index system.

Objective To introduce a new method of trans-superior limb of cerebellopontine fissure approach for exploring and managing superomedial responsible vessels of facial nerve of patients with hemifacial spasm.Methods Clinical data of 21 patients with hemifacial spasm among 183 consecutive patients were analyzed retrospectively in our hospital from February 2009 to December 2013.Dissection of the superior limb of the cerebellopontine fissure was performed to explore the distribution and the severity of compression of the superomedial responsible vessels of the facial nerve,and microvascular decompression was performed.Results Neurovascular compression was found in all of the patients,primary responsible vessels were found in 13 patients,and secondary responsible vessels were found in 8 patients.Complete spasm alleviation was achieved immediately after operation in 18 patients,and complete spasm alleviation was achieved in all of the patients 3 months after operation.No severn complications occurred and no patient died.No recurrence was noted after an average 56 months of follow-up.Conclusion The trants-superior limb of cerebellopontine fissure approach could avoid the defects of standard suboccipital retrosigrnoidal approach,which allows easy identification and management of the superomedial responsible vessels of the facial nerve of patients with hemifacial spasm;thus,high consistent successful rate and low complication rate could be found.

Objective:To develop an ex vivo normothermic mechanical perfusion(NMP)and compare the effect of air-oxygenated NMP versus oxygen-oxygenated NMP on reducing renal injury from donor after cardiac death(DCD).Methods:All kidneys from DCD rats were subjected to 30 min in situ warm ischemia after cardiac attest.And harvested kidneys were stored for 8h under static cold preservation after NMP for 2h.In experimental groups, kidneys were subjected to either air-oxygenated NMP(group A, n=6)or oxygen-oxygenated NMP(group O, n=6). Sham operation(group C, n=6)and DCD kidneys under static cold preservation without NMP(group SCS, n=6)were employed as controls.The evaluation parameters included creatinine(Cr), aspartate amino transferase(AST)and lactate dehydrogenase(LDH)in perfusate, pathological changes by hematoxylin-eosin(HE)staining, histological criteria, expressions of myeloperoxidase and intercellular adhesion molecular-1(ICAM-1)by immunohistochemistry and Western blot, tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)by enzyme-linked immunoadsorbent assay and level of malondialdehyde(MDA)by thiobarbital method and activity of superoxide dismutase(SOD)by WST-8 in renal tissues.Differences between two groups were analyzed by two-tailed unpaired Student's test and differences among more than two groups by one-way ANOVA.Results:Renal arterial oxygen tensions in NMP perfusate were(576.3±68.2)mmHg with oxygen-oxygenation and(137.0±39.1)mmHg with air-oxygenation.There was significant difference( P<0.05). The pathological injury scores in groups SCS, O and A by HE staining were(7.0±0.1), (5.0±0.9)and(2.5±0.5); injury scores and the expressions of renal proximal tubular epithelial cell vacuolar degeneration in groups O and A were lower than those in group SCS( P<0.05)and injury score in group A was lower than group O( P<0.05). In perfusate, the levels of △Cr, △AST and △LDH in groups O and A were(43.9±52.8)μmol/L and(12.6±3.5)μmol/L, (532.3±52.8)U/L and(49.1±50.4)U/L and(9998.0±2014.4)U/L and(1477.0±810.4)U/L.There were significant differences( P<0.05). In perfused kidneys, the MDA level and SOD activity in groups O and A were(0.192±0.018)mmol/g, (0.162±0.023)mmol/g, (0.6±0.3)×10 3 U/g, (1.7±0.4)×10 3 U/g; TNF-α and IL-6 levels in groups O and A were(124.376±19.635)and(89.331±13.123)ng/g, and(4.038±1.026)×10 3 and(1.774±0.518)×10 3 ng/g.After air-oxygenated NMP, lower renal damage indices were characterized by a lower MDA level and a higher SOD activity, the lower levels of TNF-α and IL-6 and the lower expressions of MPO and ICAM-1 than those in oxygen-oxygenated NMP( P<0.05). Conclusions:NMP with air-oxygenation mimics renal perfusion under physiological conditions and decreases oxidative stress and inflammation injury.It may confer a better retrieval in DCD kidney against warm ischemia injury.

Objective To analyze the clinical,laboratory and brain MRI features of patients with neurosyphilis(NS).Methods Eighty-five NS patients admitted to the Department of Neurology in Nanjing Second Hospital from November 2018 to November 2022 were retrospectively analyzed.According to the results of brain MRI,the patients were divided into two groups:normal brain MRI + unilateral lesions group and bilateral lesions group(more severe group).ROC were plotted and the areas under the curves(AUC)were calculated to evaluate the diagnostic value of clinical indicators for severe NS on MRI.Results Compared with normal brain MRI + unilateral lesions group,the mean age(P = 0.000),the rate of male(P = 0.008)and the rate of symptomatic NS(P = 0.006)were significantly higher in bilateral lesions group.Moreover,hypersensitive C-reactive protein(P = 0.028),basophil(P = 0.003),fibrinogen(P = 0.011),CSF tolulized red unheated serum test titer(P = 0.004),CSF protein concentration(P =0.000),CSF adenosine deaminase(P =0.003),and CSF white blood cell count(P =0.049)were significantly increased in patients with NS in bilateral brain lesions group.Multivariate regression analysis suggested that age(OR =1.085,P =0.019)and CSF protein concentration(OR =1.004,P =0.023)were risk factors for NS patients with bilateral brain lesions on MRI.The clinical model was established by age,CSF protein concentration,and basophil,the AUC for predicting NS patients with bilateral brain lesions could reach 0.83(95%CI:0.73-0.91,P＜0.01).Conclusions Clinical,laboratory and brain MRI examination should be integrated during the diagnosis and treatment of NS.Elderly patients and patients with high CSF protein concentration suggest severe disease,and reduction of CSF protein concentration is expected to improve the condition of NS patients.

Objective This study was to evaluate the long-term clinical efficiency of allogeneic corneal intrastromal lenticule inlay for correction of moderate and high hyperopia.Methods A prospective self-controlled case series study was adopted.Twenty-nine hyperopic patients (53 eyes) were performed with allogeneic corneal intrastromal lenticule inlays.The range of preoperative spherical equivalent was +3.75 to + 10 D,with the mean value of (+6.84±2.95)D.All the cases were followed up for 1 year.Uncorrected and best corrected visual acuity and refraction were compared between before and after operation.Corneal topography and optical coherence topography were used to examine corneal topography.Ocular response analyzer was used to evaluate the shifts of corneal hysteresis.This study followed the Helsinki declaration,and the research process was approved by the Ethic Committee of Beijing Tongren Hospital,and informed consent was signed by each donor and receptor.Results Compared with the before surgery,the uncorrected distance visual acuity (UDVA) and uncorrected near visual acuity (UNVA) were obviously improved and the spherical equivalent (SE) was obviously decresed in 3 months,6 months and 1 year after surgery,with significant differences between them (all at P＜0.05),but no significant differences were found between each postoperative time points (all at P＞0.05).One year after surgery,14 eyes (26.4％) gained one line of best corrected distance visual acuity (BCDVA),and 12 eyes (22.6％) gained two lines of BCDVA.Only 2 patients (5.66％) lost lines due to opaque lenticules,and no eye lost lines after changing the opaque lenticules.There was no obvious hyperopic fallback phenomenon.Compared with the before surgery,the average corneal curvature value (Avek) was obviously improved,the surface regularity index (SRI),surface asymmetry index (SAI) and central corneal thickness (CCT) were obviously increased in 3 months,6 months and 1 year after surgery,with significant differences between them (all at P＜0.05),but no significant differences were found between each postoperative time points (all at P ＞ 0.05).The cornea optical coherence tomography (OCT) examination showed that,after the operation,the corneal stromal implant was in place and clear.One year after surgery,the dividing line of corneal graft was still clearly visible.No significant changes of corneal hysteresis (CH) and corneal resistance factor (CRF) were seen among different time points before and after surgeries (F =1.443,P =0.216;F =1.744,P =0.128).Conclusions Allogeneic corneal small incision intrastromal lenticule inlays can be used to correct moderate and high hyperopic eye with good safety,effectiveness and predictability.It provides a new choice for hyperopic patients.

Objective:To study the impact of the Varian real-time position management (RPM) respiratory gating system on radiotherapy planning dosimetry.Methods:The radiotherapy plans of 40 cases with thoracic or abdominal tumors were retrospectively selected in this study. The motion phantom for quality control was adopted to generate respiratory gating signals, and the 30%-60% stable phase at the end of expiratory was selected as the respiratory gating window. The dose verification for the abovementioned radiotherapy plans was performed using the Portal Dosimetry (PD) system under RPM respiratory gating mode with the Edge accelerator. Afterwards, dose analysis was performed with different γ passing rate criteria and the distribution characteristics of γ values were analyzed. Finally, the verification results between the non-gating mode and the gating mode were compared.Results:Under the respiratory gating mode, the passing rates of all intensity-modulated radiation therapy/volumetric-modulated arc therapy (IMRT/VMAT) plans with or without flattening filters were over 95.5% by γ criteria of (3%, 3 mm) or (3%, 2 mm) and were over 90% by stricter γ criteria of (2%, 2 mm). All plans met the clinical requirements recommended by the American Association of Physicists in Medicine (AAPM). The passing rates of dose verification under non-gating mode were slightly better than those under respiratory gating mode, and the differences between the two modes were statistically significant (3%/3 mm, Z =-1.45; 3%/2 mm, Z =-2.86; 2%/2 mm, Z =-3.70; 1%/1 mm, Z =-4.52; P<0.05). There was no significant difference in the minimum and maximum values of γ and the share of γ > 1.5 of plan verification result under the two modes. However, the average value and standard deviation of the γ were generally smaller under the non-gating mode. Conclusions:The impact of the introduction of RPM respiratory gating technology on dose is clinically acceptable, and the execution of these plans in this gating mode is safe and reliable.