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 explore the characteristics of depression,anxiety,and stress symptoms among Chinese men who have sex with men(MSM),to determine the links of psychological resilience with these symptoms at the symptom level,and to provide insights for tailoring mental health intervention measures for MSM.Methods:A cross-sectional survey was conducted in southwestern China(Chongqing and Sichuan)from May to August 2022.The Depression,Anxiety,and Stress Scale-21 was used to assess mental health-related symptoms in MSM.Psychological resilience was evaluated using the brief version of the Connor-Davidson Resilience Scale.A regularized partial correlation network was constructed,and then a Bayesian network was established to identify potential causal rela-tionships in symptoms.A flow network was used to explore the link between psychological resilience and symptoms of anxiety,depres-sion,and stress.Results:A total of 938 MSM were included in the analysis.The proportion of MSM with depression,anxiety,and stress was 29.74%."Panic","scared","no relax",and"down-hearted"showed high expected influence.Bridging symptoms were"panic","down-hearted",and"agitated".Central and bridging symptoms also appeared at the top of the Bayesian network.Psychological resil-ience was negatively correlated with"no initiative","down-hearted","meaningless","panic",and"no relax".Conclusion:Central symptoms"panic","scared","no relax",and"down-hearted",as well as bridging symptoms"panic","down-hearted",and"agi-tated"are identified through network analysis.The potential causal priority of these symptoms is prominent.Interventions tailored to central and bridging symptoms may be effective,and interventions for enhancing psychological resilience may alleviate negative emotion-related symptoms,especially depressive symptoms in the MSM population.

Objective:To observe the clinical effect of comprehensive reconstruction of grades Ⅰ-Ⅱ thumb and finger defects with hallux osteo-onychocutaneous flaps of great toe.Methods:This is a retrospective study. From June 2020 to December 2023, comprehensive reconstruction surgery for Grade Ⅰ-Ⅱ digital defect were performed with hallux osteo-onychocutaneous flaps of great toe for 3 thumbs and 7 fingers in 9 patients in the Department of Hand and Microsurgery of Baoji Third Hospital. Causes of digital injury were: 4 of machine crush, 3 of electric saw cut, 1 of door crush, and 1 of electrical burn. There were 6 grade I digital defects (beyond the nail root) and 4 grade Ⅱ defects (last segment of digit). The defects of the digits were reconstructed by taking references of the shape and structure of the contralateral normal thumbs and fingers. Then the hallux osteo-onychocutaneous flaps of great toe were designed and harvested accordingly from the left and right great toes. Donor sites were covered by skin grafting or local dressing change. One patient was treated in emergency surgery, 6 in sub-emergency surgery and 2 in elective surgery. Integrated perioperative patient management was provided to all of the patients. Postoperative follow-ups were conducted through the visit of outpatient clinic, telephone calls or WeChat interviews. Flap survival, appearance and sensation recovery were evaluated according to the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association.Results:Vascular insufficiency of 1 digit occurred in surgery, and relieved by local treatment with lidocaine and warm saline. All 10 digits successfully survived, and all donor sites healed spontaneously. The postoperative follow-up period was 10 to 30 months, with an average of 18 months. One transferred nail was found in poor appearance (not flat), the rest of the reconstructed digits were good in appearance and function. The nail, finger print and fine sensation (TPD 5~8 mm), as well as digital flexion, extension, grasping and opposition of the reconstructed digits were all good. According to the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association, at the last follow-up visit, 5 digits were in excellent, 4 in good and 1 in fair.Conclusion:The comprehensive reconstruction of grades Ⅰ-Ⅱ digital defects with hallux osteo-onychocutaneous flap of great toe is an ideal surgical technique that can reconstruct the nail, finger print and sensation of a digit, with good postoperative function as well as an aesthetic and realistic appearance.

Objective:To evaluate the effect of prolonged cryopreservation duration of high-quality embryos on clinical outcomes.Methods:A retrospective cohort study was conducted, analyzing 8 988 frozen-thawed embryo transfer cycles performed from January 2016 to December 2023 at the Center for Reproductive Medicine, Chongqing Maternal and Child Healthcare Hospital where patients underwent endometrial preparation with artificial cycles and subsequent transfer of high-quality embryos. Embryos were divided into four groups according to the length of time they had been cryopreserved: ≤3-month group ( n=3 030), 4-6-month group ( n=3 193), 7-12-month group ( n=1 465), and >12-month group ( n=1 300). High-quality cleavage-stage embryos and blastocysts were selected according to the Istanbul Consensus and Gardner grading system. High-quality cleavage-stage embryos were defined as those graded ≤2, while high-quality blastocysts were defined as those graded ≥4BB. Generalized estimating equations were employed for multivariate analysis. Primary outcome indicator was clinical pregnancy rate, with secondary outcome indicators comprising live birth rate, miscarriage rate and preterm birth rate. Results:Significant intergroup differences were observed in baseline characteristics, including age, body mass index, anti-Müllerian hormone levels, fertilization method, endometrial thickness on transfer day, infertility etiology, infertility type, number of embryos transferred, embryo culture duration, number of eggs obtained, and preimplantation genetic testing (all P<0.05). Clinical pregnancy rates for the ≤3-month, 4-6-month, 7-12-month, and >12-month groups were 69.04% (2 092/3 030), 70.15% (2 240/3 193), 61.16% (896/1 465), and 57.69% (750/1 300), respectively, and live birth rates were 58.58% (1 775/3 030), 60.04% (1 917/3 193), 51.40% (753/1 465), and 47.00% (611/1 300), with significantly differences (all P<0.001). After adjusting for confounders via multivariate analysis, the 4-6-month group showed no statistically significant difference in clinical pregnancy rate or live birth rate compared with the ≤3-month group (clinical pregnancy: OR=0.982, 95% CI: 0.874-1.103, P=0.754; live birth: OR=0.989, 95% CI: 0.887-1.102, P=0.835). However, both the 7-12-month group (clinical pregnancy: OR=0.772, 95% CI: 0.671-0.888, P<0.001; live birth: OR=0.805, 95% CI: 0.704-0.921, P=0.002) and >12-month group (clinical pregnancy: OR=0.765, 95% CI: 0.662-0.885, P<0.001; live birth: OR=0.772, 95% CI: 0.671-0.888, P<0.001) exhibited significant decreases in clinical pregnancy rate and live birth rate. No significant differences were observed in miscarriage rate and preterm birth rate among the four groups (all P>0.05). Stratified by age, the results were consistent with the total population. Conclusion:The duration of high-quality embryo vitrification freezing exceeding 6 months is negatively correlated with clinical pregnancy rate and live birth rate, and cryostorage time should be considered as a relevant factor in embryo selection.

Objective To investigate the impact of hepatopancreatic ampulla features on difficult biliary cannulation during endoscopic retrograde cholangiopancreatography(ERCP).Methods A retrospective analysis was conducted on 800 patients who underwent ERCP from June 2023 to April 2024.Hepatopancreatic ampullary features were categorized endoscopically into four types:1)Non-protruding(n=544);2)Protruding(n=120);3)Diverticula or mucosal folds(n=96);4)Tortuosity or tumor involvement(n=40).Standard biliary cannulation was initiated in all cases,with failure defined as difficult cannulation.Advanced cannulation techniques were employed for all difficult cannulation cases[double-guidewire technique(DGT)or precutsphincterotomy(PST)].Success rates and procedural complications were recorded.Results Standard biliary cannulation outcomes,success rates 79.96％(435/544)in non-protruding vs.69.17％(83/120)in protruding,72.92％(70/96)in diverticula or mucosal folds,and 65.00％(26/40)in tortuosity or tumor groups(x2=10.90,P=0.012);Difficult cannulation rates 18.01％(98/544)in non-protruding vs.27.50％(33/120)in protruding,27.08％(26/96)in diverticula or mucosal folds,and 30.00％(12/40)in tortuosity or tumor groups(x2=10.41,P=0.015).In the subgroups,the rates of DGT intubation in the four groups were 11.95％(65/544),15.83％(19/120),12.50％(12/96),and 20.00％(8/40),respectively.There was no statistically significant difference in the success rate of DGT intubation between the groups(x2=6.96,P=0.073).In the subgroups,the PST intubation rates were 6.07％(33/544),11.67％(14/120),14.58％(14/96),and 10.00％(4/40),respectively.There was no statistically significant difference in the success rate of PST intubation between the groups(x2=5.54,P=0.136).Advanced cannulation techniques were used in 169 patients,DGT success rates of 94.23％(98/104)vs.PST at 89.23％(58/65)(x2=19.50,P=0.021);PEP incidence 18.34％(31/169)in difficult cannulation vs.2.61％(16/614)in standard group(x2=58.64,P=0.000);No significant difference in PEP between DGT(21.25％)and PST(13.85％)groups(x2=1.17,P=0.279).Conclusion Hepatopancreatic ampulla features influences biliary cannulation success.Non-protruding ampullae demonstrate optimal outcomes with standard techniques.Notably,DGT and PST are associated with elevated PEP risks in difficult cannulation.

Objective:To investigate the inhibitory effect of Huqizhengxiao decoction (HQZXD) on subcutaneous tumor in H22 hepatoma-bearing mice and its potential mechanism.Methods:Twenty-five healthy male BALB/c inbred mice aged 4 to 6 weeks and weighing (20±2) g were taken. One of them was used for the amplification of H22 hepatoma cells. The amplified H22 hepatoma cells were inoculated subcutaneously at the left posterior axillary line of the remaining mice for modeling. After subcutaneous tumor formation, the mice were randomly divided into four groups: model group, HQZXD group, sorafenib group and combined (HQZXD+ sorafenib) group, with 6 mice in each group. Tumor inhibition rates, and serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) were observed. The expression of interleukin (IL)-6, signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in tumor tissues was detected using immunohistochemistry and Western blotting. Enzyme-linked immunosorbent assay was used to quantify the levels of IL-6, tumor necrosis factor-alpha (TNF-α), and IL-1β in tumor tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA levels of IL-6, STAT3, and C-X-C motif chemokine ligand 1 (CXCL1) in tumor tissues.Results:The general condition of mice in all treatment groups improved compared to the model group. Notably, the tumor weight (0.50±0.22) g and tumor volume (0.37±0.18) cm 3 in the combined group were significantly lower than those in the model group [tumor weight: (1.63±0.26) g, tumor volume: (0.98±0.83) cm 3] with statistical significance (both P<0.05). The tumor inhibition rates for the sorafenib, HQZXD, and combination groups were 35.4%, 48.6%, and 69.7%, respectively. Compared to the model group, serum levels of AST and ALT were reduced in all treatment groups, with the combined group showing the most significant decrease [AST: (48.81±2.82) U/L vs. (188.12±6.51) U/L; ALT: (34.14±1.25) U/L vs. (116.62±4.72) U/L], and the differences were statistically significant (both P<0.05). The protein expression levels of IL-6, STAT3, p-STAT3, IL-1β, TNF-α, and NLRP3 in tumor tissues were reduced in all treatment groups compared to the model group, with the combined group showing the most marked reduction, and the differences were statistically significant (all P<0.05). Similarly, the mRNA levels of IL-6, STAT3, and CXCL1 in tumor tissues were lower in all treatment groups compared to the model group, with the combined group showing lower levels than the single treatment groups, and these differences were statistically significant (all P<0.05). Conclusion:HQZXD can inhibit the activation of IL-6/STAT3 pathway, reduce inflammation in tumors, and consequently play a certain inhibitory effect on tumor.

Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

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 evaluate the effect of prolonged cryopreservation duration of high-quality embryos on clinical outcomes.Methods:A retrospective cohort study was conducted, analyzing 8 988 frozen-thawed embryo transfer cycles performed from January 2016 to December 2023 at the Center for Reproductive Medicine, Chongqing Maternal and Child Healthcare Hospital where patients underwent endometrial preparation with artificial cycles and subsequent transfer of high-quality embryos. Embryos were divided into four groups according to the length of time they had been cryopreserved: ≤3-month group ( n=3 030), 4-6-month group ( n=3 193), 7-12-month group ( n=1 465), and >12-month group ( n=1 300). High-quality cleavage-stage embryos and blastocysts were selected according to the Istanbul Consensus and Gardner grading system. High-quality cleavage-stage embryos were defined as those graded ≤2, while high-quality blastocysts were defined as those graded ≥4BB. Generalized estimating equations were employed for multivariate analysis. Primary outcome indicator was clinical pregnancy rate, with secondary outcome indicators comprising live birth rate, miscarriage rate and preterm birth rate. Results:Significant intergroup differences were observed in baseline characteristics, including age, body mass index, anti-Müllerian hormone levels, fertilization method, endometrial thickness on transfer day, infertility etiology, infertility type, number of embryos transferred, embryo culture duration, number of eggs obtained, and preimplantation genetic testing (all P<0.05). Clinical pregnancy rates for the ≤3-month, 4-6-month, 7-12-month, and >12-month groups were 69.04% (2 092/3 030), 70.15% (2 240/3 193), 61.16% (896/1 465), and 57.69% (750/1 300), respectively, and live birth rates were 58.58% (1 775/3 030), 60.04% (1 917/3 193), 51.40% (753/1 465), and 47.00% (611/1 300), with significantly differences (all P<0.001). After adjusting for confounders via multivariate analysis, the 4-6-month group showed no statistically significant difference in clinical pregnancy rate or live birth rate compared with the ≤3-month group (clinical pregnancy: OR=0.982, 95% CI: 0.874-1.103, P=0.754; live birth: OR=0.989, 95% CI: 0.887-1.102, P=0.835). However, both the 7-12-month group (clinical pregnancy: OR=0.772, 95% CI: 0.671-0.888, P<0.001; live birth: OR=0.805, 95% CI: 0.704-0.921, P=0.002) and >12-month group (clinical pregnancy: OR=0.765, 95% CI: 0.662-0.885, P<0.001; live birth: OR=0.772, 95% CI: 0.671-0.888, P<0.001) exhibited significant decreases in clinical pregnancy rate and live birth rate. No significant differences were observed in miscarriage rate and preterm birth rate among the four groups (all P>0.05). Stratified by age, the results were consistent with the total population. Conclusion:The duration of high-quality embryo vitrification freezing exceeding 6 months is negatively correlated with clinical pregnancy rate and live birth rate, and cryostorage time should be considered as a relevant factor in embryo selection.

Objective To investigate the impact of hepatopancreatic ampulla features on difficult biliary cannulation during endoscopic retrograde cholangiopancreatography(ERCP).Methods A retrospective analysis was conducted on 800 patients who underwent ERCP from June 2023 to April 2024.Hepatopancreatic ampullary features were categorized endoscopically into four types:1)Non-protruding(n=544);2)Protruding(n=120);3)Diverticula or mucosal folds(n=96);4)Tortuosity or tumor involvement(n=40).Standard biliary cannulation was initiated in all cases,with failure defined as difficult cannulation.Advanced cannulation techniques were employed for all difficult cannulation cases[double-guidewire technique(DGT)or precutsphincterotomy(PST)].Success rates and procedural complications were recorded.Results Standard biliary cannulation outcomes,success rates 79.96％(435/544)in non-protruding vs.69.17％(83/120)in protruding,72.92％(70/96)in diverticula or mucosal folds,and 65.00％(26/40)in tortuosity or tumor groups(x2=10.90,P=0.012);Difficult cannulation rates 18.01％(98/544)in non-protruding vs.27.50％(33/120)in protruding,27.08％(26/96)in diverticula or mucosal folds,and 30.00％(12/40)in tortuosity or tumor groups(x2=10.41,P=0.015).In the subgroups,the rates of DGT intubation in the four groups were 11.95％(65/544),15.83％(19/120),12.50％(12/96),and 20.00％(8/40),respectively.There was no statistically significant difference in the success rate of DGT intubation between the groups(x2=6.96,P=0.073).In the subgroups,the PST intubation rates were 6.07％(33/544),11.67％(14/120),14.58％(14/96),and 10.00％(4/40),respectively.There was no statistically significant difference in the success rate of PST intubation between the groups(x2=5.54,P=0.136).Advanced cannulation techniques were used in 169 patients,DGT success rates of 94.23％(98/104)vs.PST at 89.23％(58/65)(x2=19.50,P=0.021);PEP incidence 18.34％(31/169)in difficult cannulation vs.2.61％(16/614)in standard group(x2=58.64,P=0.000);No significant difference in PEP between DGT(21.25％)and PST(13.85％)groups(x2=1.17,P=0.279).Conclusion Hepatopancreatic ampulla features influences biliary cannulation success.Non-protruding ampullae demonstrate optimal outcomes with standard techniques.Notably,DGT and PST are associated with elevated PEP risks in difficult cannulation.