Adenocarcinoma ; pathology ; secondary ; surgery ; Adult ; Bone Marrow Neoplasms ; diagnosis ; secondary ; Female ; Humans ; Postoperative Period ; Stomach Neoplasms ; pathology ; surgery

Aim To explore the key genes of osimertinib aequired resistanee in non-small eell lung eaneer eells based on transcriptomics, anrl to analyze the significance in osimertinib resistant eells. Methods Hu man lung cancer HI975 cells and osimertinib resistant HI 975/OR cells were cultured in vitro. The effect of osimertinib and ferroptosis inducers on cell viability was measured by CCK-8 assay. The difference in gene expression was measured by transcriptomics. Hie expression levels of ferroptosis-related proteins were measured by Western blot. Results Osimertinib j eould inhibit the proliferation of HI975 eells and HI 975/OR eells in different concentrations, and HI975 cells were more sensitive. Transcriptomics analysis revealed remarkable differences in gene expression levels between HI975 and H1975/OR cells, among which the ferroptosis pathway was most significant. Western blot assay validated that different degrees of change existed in the expression levels of ferroptosis-re- lated proteins in HLF-1 , H1975 and H1975/OR eells. After the treatment of ferroptosis inducers RSL3 and Erastin, H1975/OR cells showed higher sensitivity, while little significance was observed on HI975 cells. Conclusions There were significant differences between HI975 lung cancer cells and osimertinib resist-ant H1975/OR cells on the gene expression levels, and the ferroptosis pathway plays an important role in acquired resistance to osimertinib.

The paper is aimed to provide a novel index, named as multidimensional spatial triangular area, for the evaluation of the release-absorption correlation of multiple component traditional Chinese medicines (TCMs). The applicability of the method was demonstrated by the example data. The method and standard practice for evaluation of the release-absorption correlation for western medicines with single compound could not be applied to TCMs with multiple components. The release percentage or absorption percentage of the multiple components for TCMs at the sampling time was a point in the multidimensional space. The area of the triangle formed byt the sequential three points represented the changing characteristics of the components' release and absorption kinetics. The side lengths of the triangle could be calculated from the spatial distances between each two of the sequential three points. Then the triangle area could be obtained by the side lengths. The in vitro release-in vivo absorption correlation of the multiple components could be represented by the correlation between the integrating values of the release triangle areas and that of the absorption triangle areas. The results of the examples indicated that the multidimensional spatial triangular area method could treat the multiple components in a holistic way, in line with the holism the hi he TCMs. Therefore, the multidimensional spatial triangular area method provided new methodology for the release-absorption correlation of the TCMs with multiple components.
Algorithms ; Chemistry Techniques, Analytical ; Drug Combinations ; Drugs, Chinese Herbal ; analysis ; isolation & purification ; pharmacokinetics ; Medicine, Chinese Traditional ; Plants, Medicinal ; chemistry

OBJECTIVETo evaluate the effect and results of short and medium periods of follow-up of percutaneous balloon pulmonary valvuloplasty for critical pulmonary stenosis of neonates and infants under 6 months of age.

METHODSBetween January 2002 and December 2008, 34 consecutive patients aged from 13 to 175 days with critical pulmonary valvular stenosis underwent percutaneous balloon valvuloplasty. Patients records, catheterization data, angiograms and echocardiograms were reviewed. Patients were followed up for 6 months to 4 years (mean 25.5 months) by means of clinical examination and Doppler echocardiography.

RESULTSThe pulmonary valvuloplasty was accomplished in 32 (94%) of 34 attempts. Immediately after dilation, right ventricular systolic pressure (RVSP) decreased from (96 ± 28) mm Hg (1 mm Hg = 0.133 kPa) (49 ± 20) mm Hg (P < 0.01), the transvalvular peak to peak systolic gradient (ΔP) decreased from (89 ± 25) mm Hg to (25 ± 12) mm Hg (P < 0.01), and the right ventricular/aortic systolic pressure ratio decreased from 1.2 ± 0.5 to 0.7 ± 0.3 (P < 0.01). One patient died because of cardiac tamponade following rupture of the pulmonary valve annulus, 2 patients developed pericardial effusion, 3 patients had infundibular spasm, 3 patients had a pre-dilation by small balloon and 1 patient had weakened femoral artery pollex. After a follow up period of 6 months to 4 years 3 of 31 patients lost to follow-up. Repeat valvuloplasty was performed in 5 patients (3 neonates), no patient required surgery, and the other 23 patients did not undergo further intervention, a mean peak systolic Doppler gradient of (20 ± 13) mm Hg was found and no significant pulmonary regurgitation was seen.

CONCLUSIONSPercutaneous balloon pulmonary valvuloplasty was effective and safe for the treatment of critical pulmonary stenosis of neonates and infants under 6 months of age with good short and medium term results.

Catheterization ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Lost to Follow-Up ; Male ; Pulmonary Valve ; Pulmonary Valve Stenosis ; therapy ; Treatment Outcome

OBJECTIVETo analyze the intermediate-term results associated with the use of Zweymtiller hip system.

METHODSReview the 116 cases (142 hips) who were treated with total hip replacement from 1996 to 2002 by a single surgeon using cementless Zweymüller hip systems.

RESULTSSixty-one cases (77 hips) were followed up, 50 cases (64 hips) were evaluated both clinically and radiographically while 5 cases (6 hips) and 6 cases (7 hips) were only evaluated clinically and radiographically respectively. The average follow-up period was 7.3 years (range 5 to 11 years). The mean preoperative Harris Hip Score was 46 while the mean postoperative Harris Hip Score was 93. Distal cortical hypertrophy and medullary sclerosis were observed in 30 hips (42.3%) and 33 hips (46.5%) respectively. Heterotopic ossification arose in 45 hips (63.4%). Radiolucent lines occurred in 27 stems (38.0%) but in no cups. Radiolucent lines were mostly observed in Gruen zones 1. Osteolysis occurred in 7 cups (9.9%) and 18 stems (25.4%). Osteolysis was mostly observed in Delee Zone 3 and Gruen zone 7. In the distal Gruen zones 3, 4 and 5, no radiolucent line or osteolysis was observed. No hips had been revised, 3 cups needed revision surgery because of aseptic loosening.

CONCLUSIONThe 5-11 years follow-up results are satisfactory, but osteolysis is common.

Adolescent ; Adult ; Aged ; Arthroplasty, Replacement, Hip ; Female ; Follow-Up Studies ; Hip Prosthesis ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult

Objective: To explore the sensitivity and specificity of the Chinese version of the volume and viscosity swallowing test with modified safety and effectiveness indicators (VVST-CV) in assessing deglutition disorders. Methods: The solvent, volume, viscosity, and test index of the volume and viscosity swallowing test were modified before it was used to evaluate 89 patients with swallowing disorders. The positive rates of the safety indexes (coughing, voice changes and blood oxygen saturation decline at least 3%) and the efficiency indexes (poor lip closure, oral residue, pharynx residue and swallowing) were recorded and compared and compared with the positive rates of penetration, aspiration and food residue determined by means of according to the videofluoroscopic swallowing study, then the sensitivity, specificity, positive predictive value and negative predictive value of the modified VVST-CV with regard to the safety and efficiency of swallowing were calculated. Results: The VVST-CV′s sensitivity in detecting dysphagia was 0.97. For impaired safety it was 0.85 and for impaired swallowing efficiency it was 0.95. The sensitivity of the coughing index was 0.65, that of sound change was 0.60 and that of oxygen saturation decrease was 0.42. The positive predictive values for coughing, sound change and oxygen saturation decrease were 0.98, 0.94 and 0.94, respectively. Conclusion The VVST-CV is simple, feasible and sensitive. It can be widely useful in the evaluation of dysphagia in clinical practice.

Animals ; Cell Proliferation ; Hepatic Stellate Cells ; Liver Cirrhosis/metabolism* ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Rats

Ventricular fibroblasts were cultured using conditioned growth medium for ventricular fibroblasts (FCGM). The rate of the total collagen synthesis of ventricular fibroblasts was measured by assaying the incorporation rate of ［3H］-proline, whereas the proliferation of ventricular fibroblasts was assessed by determining the incorporation rate of ［3H］-TdR and the expression of c-fos genes. FCGM significantly increased the ［3H］-proline incorporation rate and ［3H］-TdR incorporation rate of fibroblasts in a dose-dependent manner. Furthermore, FCGM promoted the c-fos gene expression of fibroblasts, which attained its maximum in 1 h. BQ123, an ETA receptor antagonist, partially blocked the above effects of FCGM, but AT1 receptor antagonist CV11974 and α-adrenergic receptor antagoist regitin did not. It is suggested that the ventricular fibroblast has an autorine function in promotion of collagen synthesis and proliferation of fibroblasts by secreting endothelin and other bioactive substances.

Using cell culture, radioimmunoassay for endothelin and RT-PCR, the effect of aldosterone on the endothelin secretion of ventricular fibroblasts was studied. The results showed that aldosterone (1×10－7 mol/L) promoted the expression of ppET-1 mRNA, which began to increase in 2 hours and attained the highest level in 4 hours, thereafter decreased; aldosterone increased the endothelin level in ventricular fibroblasts and fibroblast conditioned growth medium (FCGM) as well, which was blocked by spironolactone (1×10－6 mol/L), an aldosterone receptor antagonist. The results suggest that aldosterone can increase endothelin secretion by ventricular fibroblasts, which can be inhibited by its receptor antagonist spironolactone.

The aim of this study was to examine the effects of L-arginine, a nitric oxide (NO) precursor, on protein expression of endothelial nitric oxide (eNOS), nitrite/nitrate content, protein expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) and the activity of mitogen-activated protein kinase (MAPK) in cardiac tissues in renovascular hypertensive rats (RHR). The Goldblatt renovascular hypertensive model was established by two-kidney one clip method. The rats were divided into four groups, respectively treated with 50, 150 and 450 mg/kg L-arginine and 150 mg/kg L-arginine plus 10 mg/kg L-NAME (an eNOS inhibitor) (ip). Another group did not receive specific treatment from the 5th week after renal artery constriction. Control group was sham-operated. Mean arterial blood pressure (MABP) and the ratio of left ventricular weight to body weight (LVW/BW) were measured 8 weeks after treatment. eNOS protein expression, nitrite/nitrate content, MKP-1 protein expression and MAPK activity in cardiac tissues were detected using Western blot analysis, enzyme-reduction method and substrate in-gel kinase assay, respectively. It was found that L-arginine significantly inhibited the increase of MABP and LVW/BW, attenuated the activity of MAPK, increased protein expression of eNOS and MKP-1 and potentiated production of NO in cardiac tissue with the most effective dosage of 150 mg/kg, and these effects of L-arginine could be inhibited by L-NAME. These results suggest that MKP-1 may play an important role in the NO-induced inhibition of myocardial hypertrophy. The anti-hypertrophic effects of L-arginine may involve increase of eNOS protein expression and NO production, poten- tiation of MKP-1 protein expression, and inhibition of MAPK activity in the cardiac tissue of RHR.