Liver cancer is one of the most common malignant tumors worldwide. Currently, the available treatment methods cannot fully control its recurrence and mortality rate. Establishing appropriate animal models for liver cancer is crucial for developing new treatment technologies and strategies. The patient-derived xenograft (PDX) model preserves the tumor's microenvironment and heterogeneity, which makes it advantageous for biological research, drug evaluation, personalized medicine, and other purposes. This article reviews the development, preparation techniques, application fields, and challenges of PDX models in liver cancer, providing insights for the research and exploration of PDX models in diagnostic and therapeutic strategies of liver cancer.
Liver Neoplasms/drug therapy* ; Animals ; Humans ; Xenograft Model Antitumor Assays/methods* ; Mice ; Disease Models, Animal

Objective:To establish a tumor tissue xenograft (PDX) model derived from liver cancer patients and explore the factors affecting tumorigenicity of liver cancer in the PDX model.Methods:The hepatocellular carcinoma tissues were inoculated subcutaneously in the axilla of NPG mice using the tissue block method to establish a PDX model. The demographic characteristics and related clinical examination data of 60 hepatocellular carcinoma patients were collected using the electronic medical record system and comprehensive medical information system of Beijing You'an Hospital, affiliated to Capital Medical University. The hepatocellular carcinoma samples of 24 cases were sequenced using the Oak Wing TM-808 gene detection reagent and high-throughput sequencing technology. SPSS 17.0 statistical software was used for statistical analysis, and the count data were analyzed using the χ2 test. Results:The tumorigenicity rate of PDX samples from 60 patients with liver cancer was 35% (21/60). The average tumorigenic duration in the PDX-P0 generation was 110.71±50.45 days. There were statistically significant differences ( P<0.05) corresponding to Edmondson grade ( χ2=5.910, P=0.015) and Ki67 expression ( χ2=4.615, P=0.032) among PDX with tumorigenicity and without tumorigenicity between the liver cancer samples. There was no statistically significant difference in gene mutation (TOP25) among PDX with tumorigenicity and without tumorigenicity between liver cancer samples. Conclusion:The factors affecting the tumorigenicity of liver cancer in PDX models are complex. The high pathological grade and strong Ki67 expression may be the key factors for the completion of liver cancer in PDX models.

Objective:To establish a tumor tissue xenograft (PDX) model derived from liver cancer patients and explore the factors affecting tumorigenicity of liver cancer in the PDX model.Methods:The hepatocellular carcinoma tissues were inoculated subcutaneously in the axilla of NPG mice using the tissue block method to establish a PDX model. The demographic characteristics and related clinical examination data of 60 hepatocellular carcinoma patients were collected using the electronic medical record system and comprehensive medical information system of Beijing You'an Hospital, affiliated to Capital Medical University. The hepatocellular carcinoma samples of 24 cases were sequenced using the Oak Wing TM-808 gene detection reagent and high-throughput sequencing technology. SPSS 17.0 statistical software was used for statistical analysis, and the count data were analyzed using the χ2 test. Results:The tumorigenicity rate of PDX samples from 60 patients with liver cancer was 35% (21/60). The average tumorigenic duration in the PDX-P0 generation was 110.71±50.45 days. There were statistically significant differences ( P<0.05) corresponding to Edmondson grade ( χ2=5.910, P=0.015) and Ki67 expression ( χ2=4.615, P=0.032) among PDX with tumorigenicity and without tumorigenicity between the liver cancer samples. There was no statistically significant difference in gene mutation (TOP25) among PDX with tumorigenicity and without tumorigenicity between liver cancer samples. Conclusion:The factors affecting the tumorigenicity of liver cancer in PDX models are complex. The high pathological grade and strong Ki67 expression may be the key factors for the completion of liver cancer in PDX models.

OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.

Objective:To investigate the differences in acoustic characteristics between older patients with dysarthria resulting from anterior and posterior circulation cerebral infarctions.Methods:A case-control study was conducted.Sixty hospitalized older patients with dysarthria were selected and divided into two groups: the anterior circulation cerebral infarction group and the posterior circulation cerebral infarction group, each comprising 30 cases.Additionally, thirty healthy individuals aged 65 and above were included as a control group.The subjective evaluation of the patients' overall phonetic function was conducted using the GRBAS scale.Objective parameters, including fundamental frequency(F0), Jitter, Shimmer, maximum phonation time(MPT), maximum sound pressure level(SPLmax), minimum sound pressure level(SPLmin), and the dysphonia severity index(DSI), were collected using the DIVAS2.5 voice analysis system.We analyzed the acoustic characteristics across the three groups: patients with dysarthria and healthy subjects.Results:The grade(G), roughness(R), breathiness(B), asthenia(A), and strain(S)scores of patients in both the anterior and posterior circulation cerebral infarction groups were significantly higher than those of the healthy control group( F=16.574, 39.793, 46.309, 52.154, 25.603; all P<0.001).Furthermore, the roughness(R)and strain(S)of the voice in the anterior circulation cerebral infarction group were significantly elevated compared to the posterior circulation cerebral infarction group, whereas the breathiness(B), asthenia(A), and grade(G)scores in the posterior circulation cerebral infarction group were significantly higher than those in the anterior circulation cerebral infarction group(all P<0.001).The fundamental frequency value(F0)of the voice in patients with anterior circulation cerebral infarction was significantly greater than that of both the posterior circulation cerebral infarction group and the healthy control group( F=39.050, P<0.001).In contrast, the fundamental frequency value(F0)of patients with posterior circulation cerebral infarction was lower than that of the healthy control group( P=0.003).Additionally, the Jitter value in the anterior circulation cerebral infarction group was higher than in both the posterior circulation cerebral infarction group and the healthy control group( F=64.976, P<0.001).The Shimmer value in the anterior circulation cerebral infarction group was lower than that in the posterior circulation cerebral infarction group but higher than that in the healthy control group(both P<0.001).Finally, the values of MPT, SPLmin and SPL max, DSI in the anterior circulation cerebral infarction group were higher than those in the posterior circulation cerebral infarction group and lower than those in the healthy control group( F=90.406, 24.003, 16.164; all P<0.001); the value of DSI in the anterior circulation cerebral infarction group was lower than in both the posterior circulation cerebral infarction group and the healthy control group( F=87.921, P<0.001). Conclusions:There are notable differences in the acoustic characteristic parameters of dysarthria resulting from injuries at various anatomical sites in older patients with cerebral infarction.In practical clinical settings, a comprehensive evaluation of dysarthria in these patients should integrate the anatomical location of the injury, subjective symptom assessment, and objective analysis of acoustic characteristics to inform precise and personalized rehabilitation strategies.

Objective:To investigate the differences in acoustic characteristics between older patients with dysarthria resulting from anterior and posterior circulation cerebral infarctions.Methods:A case-control study was conducted.Sixty hospitalized older patients with dysarthria were selected and divided into two groups: the anterior circulation cerebral infarction group and the posterior circulation cerebral infarction group, each comprising 30 cases.Additionally, thirty healthy individuals aged 65 and above were included as a control group.The subjective evaluation of the patients' overall phonetic function was conducted using the GRBAS scale.Objective parameters, including fundamental frequency(F0), Jitter, Shimmer, maximum phonation time(MPT), maximum sound pressure level(SPLmax), minimum sound pressure level(SPLmin), and the dysphonia severity index(DSI), were collected using the DIVAS2.5 voice analysis system.We analyzed the acoustic characteristics across the three groups: patients with dysarthria and healthy subjects.Results:The grade(G), roughness(R), breathiness(B), asthenia(A), and strain(S)scores of patients in both the anterior and posterior circulation cerebral infarction groups were significantly higher than those of the healthy control group( F=16.574, 39.793, 46.309, 52.154, 25.603; all P<0.001).Furthermore, the roughness(R)and strain(S)of the voice in the anterior circulation cerebral infarction group were significantly elevated compared to the posterior circulation cerebral infarction group, whereas the breathiness(B), asthenia(A), and grade(G)scores in the posterior circulation cerebral infarction group were significantly higher than those in the anterior circulation cerebral infarction group(all P<0.001).The fundamental frequency value(F0)of the voice in patients with anterior circulation cerebral infarction was significantly greater than that of both the posterior circulation cerebral infarction group and the healthy control group( F=39.050, P<0.001).In contrast, the fundamental frequency value(F0)of patients with posterior circulation cerebral infarction was lower than that of the healthy control group( P=0.003).Additionally, the Jitter value in the anterior circulation cerebral infarction group was higher than in both the posterior circulation cerebral infarction group and the healthy control group( F=64.976, P<0.001).The Shimmer value in the anterior circulation cerebral infarction group was lower than that in the posterior circulation cerebral infarction group but higher than that in the healthy control group(both P<0.001).Finally, the values of MPT, SPLmin and SPL max, DSI in the anterior circulation cerebral infarction group were higher than those in the posterior circulation cerebral infarction group and lower than those in the healthy control group( F=90.406, 24.003, 16.164; all P<0.001); the value of DSI in the anterior circulation cerebral infarction group was lower than in both the posterior circulation cerebral infarction group and the healthy control group( F=87.921, P<0.001). Conclusions:There are notable differences in the acoustic characteristic parameters of dysarthria resulting from injuries at various anatomical sites in older patients with cerebral infarction.In practical clinical settings, a comprehensive evaluation of dysarthria in these patients should integrate the anatomical location of the injury, subjective symptom assessment, and objective analysis of acoustic characteristics to inform precise and personalized rehabilitation strategies.

Objective:To investigate the molecular mechanism of sorafenib against hepatocellular carcinoma.Methods:Sorafenib efficacy was screened and verified by the hepatocellular carcinoma patient-derived tumor xenograft (PDX) model. Veterinary B-mode ultrasonography and in vivo confocal laser scanning microscopy were used to observe PDX angiogenesis. Immunohistochemistry was used to observe the expression of proliferation and angiogenesis-related proteins in PDX tissue. Real-time quantitative PCR technology was used to observe the RUNX3 gene in PDX tissues. SPSS 17.0 statistical software was used for statistical analysis.Results:Four cases of PDX were used to screen the efficacy of sorafenib. PDX1 had a significant response to sorafenib, with an inhibition rate of 68.07%. Compared with the control group, sorafenib had significantly inhibited PDX1 relative tumor volume (5.76±2.14 vs. 11.71±2.87, P<0.05). Cell division index (39.50±7.72 vs. 67.10±9.14, P<0.05) and Ki67 expression (288.6±43.40 vs. 531.70±55.60, P<0.05) were significantly decreased. Veterinary B-mode ultrasonography showed evident blood flow signals in PDX1 tumors. In vivo confocal laser scanning microscopy results showed that sorafenib had significantly reduced the total vessel length (1573.00±236.21 vs. 2675.03±162.00, P<0.05) and area (11 145.33±1931.97 vs. 20 105.37±885.93, P<0.05)) of PDX1 tumors. Immunohistochemical results showed that sorafenib had significantly down-regulated the protein expressions of CD34 (27.55±3.76 vs. 45.47±5.57, P<0.05), VEGF (16.33±2.86 vs. 22.77±3.20, P<0.05) and MVD (38.75±6.01 vs. 55.50±8.61, P<0.05). Real-time PCR results showed that sorafenib had significantly up-regulated RUNX3 gene expression (2.14±0.71 vs. 1.00±0.36, P<0.05). However, there was a negative correlation between the expression of RUNX3 gene and the ratio of VEGF-positive cells in sorafenib group ( R2=0.509 7). Conclusion:Sorafenib may inhibit the PDX angiogenesis and the growth of hepatocellular carcinoma by regulating the RUNX3-VEGF pathway.

Objective? To investigate the effects of nursing quality improvement in chest pain center on patients with ST-segment elevation myocardial infarction (STEMI). Methods? A total of 93 patients with STEMI who received routine nursing care from July to December 2016 (n=30) and optimized quality nursing care from January to July 2017 (n=63) in the First Affiliated Hospital of He＇nan University of Traditional Chinese Medicine were enrolled to the study. The patients＇ gender, age, and 18-lead ECG completion time, Door-To-Balloon time (D2B), myocardial injury marker report time, and their hospitalization days (d), were compared between the two groups. Results? The differences in the indicators including sex,age and 18-leads ECG completion time were not statistically different (P＞0.05). However, the differences in hospitalization time, D2B time, and myocardial injury marker report time had statistical significance (P＜ 0.05). Conclusions? The optimizing project of nursing quality management, including the optimization of nursing document writing, specialized instrument operation process and ward management index, can reduce patients＇ hospital stay, D2B time, and myocardial injury marker report time, hence improve the overall treatment quality for the patients.

Objective To clarify the impact of pre-and postnatal iron deficiency on children's motor development.Methods This was a longitudinal follow-up study.A total of 114 infants (58 boys,56 girls) born from April 2010 to December 2011 in Fuyang district of Hangzhou were enrolled.Based on cord blood and 9-month iron status,subjects were divided into prenatal iron deficiency (34 children),postnatal iron deficiency (37 children) and non-iron deficiency group (43 children).Peabody Developmental Motor Scale and BOT2-simplified version were used to evaluate the motor capacity in infants and preschoolers at 9 months,18 months and 5 years,respectively.Hierarchical linear modeling (HLM) was used to investigate the trajectory of motor development with age,the influence of different timing of early iron deficiency on children's motor development,and the differences (adjusted for possible confounding factors) in motor development in children with pre-or postnatal iron deficiency or non-iron deficiency in different family educational environment.Results At the age of 9 months,18 months and 5 years,107,109,and 114 children were evaluated respectively.After controlling for a variety of confounding factors,it was found that children with prenatal iron deficiency had significantly lower scores of motor development compared with non-iron deficiency children (52.04 vs.54.05 scores,β =-2.01,P=0.007),and that children with postnatal iron deficiency had similar scores of motor development compared with non-iron deficiency children,showing no significant difference (53.07 vs.54.05 scores,β=-0.98,P=0.180).Regardless of the maternal education status,prenatal iron deficiency children always had lower motor scores than non-iron deficiency children (49.86 vs.52.15 and 49.58 vs.51.58 scores,β=-2.29,-2.00;P=0.031,0.049).Among the non-iron deficiency children,those whose mothers had a higher education level had higher motor scores compared with those whose mothers had a lower education level (52.45 vs.50.46 scores,β=1.99,P=0.035).Conclusions The motor development of children with prenatal iron deficiency did not catch up with their counterparts without iron deficiency by 5 years of age.The results indicate the importance of preventing iron deficiency in the fetus.

Objective To compare the diagnostic value of Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI and contrast-enhanced ultrasound (CEUS) in detection of small hepatocellular carcinoma (sHCC).Methods A total of 22 patients with 29 lesions who underwent Gd-EOB-DTPA enhanced MRI and CEUS scan,and confirmed as sHCCs by pathology were included in this study.Gd EOB DTPA enhanced MRI pattern for the conclusive diagnosis of sHCC were lesions showed iso or low signal on T1 WI,showed slightly high signal or high signal on T2 WI,showed high signal on DWI and obviously enhanced in the arterial phase and/or clearance in the hepatobiliary phase;CEUS pattern for the conclusive diagnosis of sHCC were rapidly increasing in the arterial phase and showing low echo in the delay phase.Results The diagnostic sensitivity of detecting sHCC by Gd EOB-DTPA enhanced MRI and CEUS were 82.76％ and 65.52％ respectively,and there was no statistical difference (x2 =2.248,P=0.134),the diagnosis specificity were both 100 ％.Conclusion Both of the diagnostic sensitivity and specificity for detecting sHCC by Gd EOB DTPA enhanced MRI and CEUS showed no difference,the value of diagnostic sensitivity of the former is higher.