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 compare the difference and consistency between OPD-Scan Ⅲ and IOL-Master 700 in the measurement of corneal curvature(flat keratometry,K1 and steep keratometry,K2)and horizontal corneal diameter(white-to-white(WTW)distance).Methods Totally 268 patients with 328 eyes(164 right eyes and 164 left eyes)who underwent cataract surgery at the Department of Ophthalmology of the Aerospace Centre Hospital from October 2021 to September 2022 were selected for this study.The K1,K2,and WTW values of the sampled right or left eyes were measured and analyzed using OPD-Scan Ⅲ and IOL-Master 700,respectively.Parameter comparisons were performed through paired t-tests;correlations between parameters were detected through the Pearson correlation analysis;and the Bland-Altman method and intragroup correlation coefficient(ICC)analysis were employed to determine the consistency of parameter measurements between the two instruments.Results The K1 and K2 values measured by OPD-Scan Ⅲ were greater than those measured by IOL-Master 700,while the WTW values were lower than those measured by IOL-Master 700,but the differences were statistically significant(all P＜0.001).K1,K2,and WTW values measured by OPD-Scan Ⅲ were positive-ly correlated with the corresponding values measured by IOL-Master 700,and the differences were statistically significant(all P＜0.001).The proportions of K1,K2,and WTW values outside the 95％limits of agreement for both instruments were within 5％,but the absolute value of the difference in values within the 95％limits of agreement was close to or more than(1.0)D,indicating a sizeable clinical deviation.ICC analysis confirmed a good consistency between K1 and K2 values of the left and right eyes measured by the two instruments(ICC＞0.90).The difference in WTW values measured by the two instruments was significantly correlated with K2 values(both P＜0.05).There were 5 samples(83.33％)outside the positive deviation range of WTW values,of which K2 measured by IOL-Master 700 was above 47.03.Conclusion The OPD-Scan Ⅲ and IOL-Master 700 have been found to have measurement biases when assessing K1,K2 and WTW.In clini-cal practice,the two instruments cannot be interchanged as an alternative to each other.The WTW values measured by IOL-Master 700 are greater than those obtained by OPD-Scan Ⅲ;when K2≥47.03,the WTW values may not be reliably ref-errable.

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 epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.

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Objective To explore the effect of PRECEDE nursing model in elderly patients with chronic hepatitis B.Methods Eighty-six elderly patients with chronic hepatitis B in 302 military hospital from June 2015 to June 2016 were selected. The participants were divided into two groups according to the random number table. The intervention group received PRECEDE model nursing while the control group received routine nursing care. The therapeutic effect, compliance, and quality of life were compared between the two groups. Results The intervention group had significantly higher total effective rate compared with the control group (97.67% vs. 88.37%; χ2=6.604,P<0.05). The intervention group had better diet, exercise, compliance, smoking and drinking control, and regular review compared with the control group (P<0.05). There was no significant difference in the quality of life between two groups before the intervention (P>0.05). However, after the intervention, the body function, social function, psychological function, substance function and the total score of the quality of life were significantly higher in the intervention group compared with the control group (P<0.05).Conclusions PRECEDE model can significantly improve the liver function of elderly patients with chronic hepatitis B. It can promote patients' compliance and quality of life, which should be further developed in clinical practice.

Objective To investigate the mechanisms of erythropoietin-producing hepatocellular A3 (EphA3) in the invasion of hepatocellular carcinoma (HCC) cells.Methods Hepatic cell HL-7702 and HCC cell and HCC cell lines HepG2 and MHCC97H were cultured.The expression of EphA3 in the HepG2 and MHCC97H cells was suppressed by siRNA interference,and then were divided into the untreated group,the control group and the siRNA intervention group.The expression of EphA3 was detected by RT-PCR and Western blot.The invasion ability of HepG2 and MHCC97H was detected by Transwell chamber.The protein expression of VEGF and activity of vascular endothelial growth factor (VEGF) were detected by western blot and ELISA.All data were analyzed using the analysis of variance or LSD-t test.Results The relative mRNA expressions of EphA3 in HL-7702,HepG2,and MHCC97H cells were 0.94 ±0.13,1.76 ±0.16 and 3.62 ±0.14,respectively,and the protein expressions of EphA3 in the 3 cells were 0.96 ±0.12,1.59 ±0.11 and 3.82 ±0.11.There was significant difference in the EphA3 expression between HL-7702 cells and HepG2,MHCC97H cells (t =2.511,6.437 ; 2.321,6.895,P ＜ 0.05).The relative mRNA expressions of EphA3 in the HepG2 cells in the untreated group,the control group and the siRNA intervention group were 0.95 ±0.11,0.96 ±0.12 and 0.31 ±0.15,respectively.There was significant difference in the mRNA expression of EphA3 in the HepG2 cells between the siRNA intervention group and the control group (t =4.051,P ＜ 0.05).The relative mRNA expressions of EphA3 in the MHCC97H cells in the untreated group,the control group and the siRNA intervention group were 0.97 ± 0.16,0.95 ± 0.14 and 0.40 ± 0.11,respectively.There was significant difference in the mRNA expression of EphA3 in the MHCC97H cells between the siRNA interference group and the control group (t =5.237,P ＜0.05).The relative protein expressions of EphA3 in the HepG2 cells in the untreated group,the control group and the siRNA intervention group were 0.97 ± 0.16,0.95 ± 0.15 and 0.32 ± 0.17,respectively.There was significant difference in the protein expression of EphA3 in the HepG2 cells between the siRNA interference group and the control group (t =4.145,P ＜ 0.05).The relative protein expressions of EphA3 in the MHCC97H cells in the untreated group,the control group and the siRNA intervention group were 0.95 ± 0.11,0.96 ± 0.12 and 0.38 ±0.17,respectively.There was significant difference in the protein expressions of EphA3 in the MHCC97H cells between the siRNA interference group and the control group (t =4.327,P ＜ 0.05).The numbers of HepG2 cells penetrated the Watrigel in the untreated group,the control group and the siRNA intervention group were (111 ±4)/10HPF,(109 ±5)/10HPF and (51 ±3)/10HPF,respectively.There was significant difference in the number of HepG2 cells between the siRNA interference group and the control group (t =7.582,P ＜ 0.05).The numbers of MHCC97H cells penetrated the Watrigel in the untreated group,the control group and the siRNA intervention group were (402 ± 6)/10HPF,(397 ± 7)/10HPF and (152 ± 7)/10HPF,respectively.There was significant difference in the number of MHCC97H cells between the siRNA interference group and the control group (t =9.479,P ＜ 0.05).The relative protein expressions of VEGF in the HepG2 cells in the untreated group,the control group and the siRNA intervention group were 0.98 ± 0.11,0.96 ± 0.13 and 0.57 ± 0.11,respectively.There was significant difference in the protein expression of VEGF of the HepG2 cells between the siRNA interference group and the control group (t =3.167,P ＜ 0.05).The relative protein expression of VEGF in the MHCC97H cells in the untreated group,the control group and the siRNA intervention group were 0.97 ±0.14,0.98 ±0.12 and 0.34 ± 0.15,respectively.There was significant difference in the protein expression of VEGF of the MHCC97H cells between the siRNA interference group and the control group (t =4.278,P ＜ 0.05).The relative activities of VEGF proteins of HepG2 cells in the untreated group,the control group and the siRNA intervention group were 0.96 ±0.15,0.94 ±0.11 and 0.47 ±0.13,respectively.There was significant difference in the activity of VEGF protein in the HepG2 cells between the siRNA interference group and the control group (t =3.981,P ＜ 0.05).The relative activities of VEGF proteins in MHCC97H cells in the untreated group,the control group and the siRNA intervention group were 0.98 ±0.12,0.97 ±0.12 and 0.38 ±0.14,respectively.There was significant difference in the activity of VEGF protein in the MHCC97H cells between the siRNA interference group and the control group (t =4.059,P ＜ 0.05).Conclusions EphA3 plays an important role in the invasion of HCC cells via regulating the protein expression and activity of VEGF.EphA3 might be a new target for the treatment of HCC.