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 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

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

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

OBJECTIVETo study the role of a pathologic niche inducing mouse embryonic stem cells (ESC) to express hepatic cell functions in vitro.

METHODSEmbryoid bodies were developed from 5 to 7 day hanging-drop culture of mouse ESC, and their dissociated cells were planted in three differential systems: nothing added; with 20 ng/ml hepatocyte growth factor (HGF); and 5% rat cholestatic serum plus 20 ng/ml HGF added. Their differentiation was observed with inverted microscopes daily, and their hepatic functions were analyzed against their synthesis of glycogen, triglycerides, albumin, and urea nitrogen, and by their staining of indocyanine green (ICG) and fluorescein diacetate (FDA).

RESULTSESC spontaneous differentiation was hardly being controlled to form three germ layers. HGF prompted the ESC to develop further into visceral endoderm and mesoderm (myocardium), but both of them only expressed a low level of hepatocyte-specific metabolic functions. With cholestatic serum added into the HGF-induced system, differentiated cells grew into similar angular cells, and had a higher level synthesis of glycogen, triglycerides, albumin and urea nitrogen with positive ICG and FDA staining.

CONCLUSIONSSpontaneous or HGF-induced ESC differentiation has only limited hepatic functions expressed. A pathologic niche in vitro induces ESC to develop into hepatic lineages, with a higher level of hepatic metabolic functions.

Animals ; Cell Differentiation ; physiology ; Cells, Cultured ; Cholestasis ; blood ; Culture Media ; pharmacology ; Embryo, Mammalian ; Hepatocytes ; cytology ; Mice ; Serum ; Stem Cells ; cytology

Objective: To explore the expression of the N-methyl-D-aspartate (NMDA) receptor in the rat model of orchialgia and its possible mechanisms. METHODS: According to Yoshioka's method, the male rats in the control group were injected with 0.2 ml saline, and those in the experimental group with 0.2 ml 2% acetic acid solution. Then we tested the behavioral responses of the rats and determined the expressions of the subunits NR1 and NR2B of the NMDA receptor in the dorsal root ganglion and spinal dorsal horn by Western blot, RT-qPCR and immunofluorescence staining. RESULTS: The withdrawal latency was decreased in the model rats, reaching the lowest value at 4 hours after modeling, significantly lower than in the controls (［4.15 ± 0.84］ vs ［12.32 ± 1.05］, P < 0.05). Compared with the controls, the model rats showed remarkably increased mRNA and protein expressions of NR2B in the dorsal root ganglion (P < 0.05) but not in the spinal dorsal horn at 4 hours. However, no statistically significant difference was found in the expression of NR1 either in the dorsal root ganglion or in the spinal dorsal horn between the two groups (P > 0.05). CONCLUSIONS The NMDA receptor plays an important role in pathogenesis of orchialgia in rats. In the early stage of pain, upregulating the expression of the subunit NR2B of the NMDA receptor can mediate peripheral hyperalgesia and consequently orchialgia.

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.