Precision therapy has become an important approach in modern medicine,with the goal of providing individualized treatment according to the characteristics of individual patients.The successful development of precision medicine depends on the application of preclinical cancer models.Patient-derived organoid(PDO)xenograft models display characteristics of both PDO models and in vivo patient-derived tumor xenograft models.This type of model can not only maintain the heterogeneity of the original tumor,but also has additional advantages,such as large-scale cultivation,high-throughput drug screening in vitro and drug sensitivity testing in vivo.It is an innovative,precise preclinical disease model.In this review,we summarize the basic characteristics of the PDO xenograft model,analyze its construction method and influencing factors,further discuss its application in precision therapy,with the aim of providing a reliable preclinical experimental tool for individualized cancer treatment.

BACKGROUND:The patient underwent multiple hypoproteinemia after total hip arthroplasty,which affected postoperative healing and rehabilitation.OBJECTIVE:To investigate and screen the risk factors for hypoproteinemia after total hip arthroplasty,and to establish a nomogram prediction model so as to provide guidance for judging whether hypoproteinemia occurs after total hip arthroplasty.METHODS:A total of 355 patients who underwent total hip arthroplasty were included,and according to whether hypoproteinemia occurred on the first day after surgery,they were divided into 238 cases in the hypoproteinemia group and 117 cases in the normal group,with a hypoproteinemia rate of 67％.Data were collected,including age,gender,diabetes mellitus,hypertension,hyperuricemia,hyperlipidemia,anesthesia method,preoperative leukocytes,preoperative erythrocytes,preoperative hemoglobin,preoperative platelets,preoperative plasma prothrombin time,preoperative activated partial prothrombin time,preoperative international normalized ratio,preoperative thrombin time,preoperative fibrinogen,preoperative erythrocyte sedimentation rate,preoperative C-reactive protein,preoperative D-dimer,preoperative mean corpuscular hemoglobin content,preoperative mean corpuscular volume,operation time,body mass index,preoperative procalcitonin,and preoperative hematocrit.SPSS 27.0 software was used for univariate analysis,followed by R language(4.3.1)to perform least absolute shrinkage and selection operator regression and 10-fold cross-validation of the observation indicators to obtain the intersection of the two risk factors.SPSS 27.0 software was used to perform multivariate binary logistic regression to obtain the final risk factors.The prediction model of hypoproteinemia after total hip arthroplasty was constructed by R language.The receiver operating characteristic curve,calibration curve,and clinical decision curve were constructed to assess the predictive model predictive ability.RESULTS AND CONCLUSION:(1)Univariate analysis,least absolute shrinkage and selection operator regression,and multivariate logistic regression were used to screen out significant differences in age(OR=1.024,P=0.023),preoperative platelets(OR=0.995,P=0.028),and preoperative erythrocyte sedimentation rate(OR=1.031,P=0.045)in judging whether hypoproteinemia would occur after surgery(P＜0.05).(2)The nomogram prediction model was constructed based on the final risk factors screened by multivariate Logistic regression,and the prediction ability of the model was evaluated by constructing the receiver operating characteristic curve,and the area under the calculated receiver operating characteristic curve reached 0.835(95％CI=0.779-0.891),C-index=0.835.A threshold of 0-0.83 could bring better clinical efficacy calculated by the decision curve analysis.The model has good sensitivity and accuracy,which can better identify the risk of postoperative hypoproteinemia for medical staff and patients before total hip arthroplasty.

Objective:To investigate the effect of GBP3 on replication of adult T-lymphocytic leukemia virus type 1(HTLV-1).Methods:Expression of GBP3 in HTLV-1-infected HeLa cell and THP1 cell was detected by Western blot.The knock-down efficiency of siRNAs targeting GBP3 in HeLa and THP1 cells was evaluated by Western blot.Effects of GBP3 overexpression or knockdown on expression of HTLV-1 proviral transcripts Tax,px,HBZ,Gag,ENV,5'UTR,and viral proteins Tax,p19 were investigated by RT-qPCR and Western blot.GTPase-defective mutant of GBP3,GBP3K51A was constructed to explore whether the effects of GBP3 on HTLV-1 infection were dependent on its GTPase activity.Results:GBP3 expression was upregulated in HTLV-1 infected HeLa and THP1 cells.GBP3 overexpression decreased expression of HTLV-1 proviral transcripts and viral proteins,whereas the knockdown of GBP3 has the opposite effects.Overexpression of GBP3K51A increased expression of HTLV-1 proviral transcripts and viral proteins.Conclusion:HTLV-1 virus infection can induce expression of GBP3;overexpression of GBP3 inhibits virus replication and may depend on GTPase.

Objective:To develop the Discharge Readiness Scale for Patients with Chronic Skin Wounds and evaluate its reliability and validity.Methods:The Discharge Readiness Scale for Patients with Chronic Skin Wounds was developed through literature review, semi-structured interviews, Delphi expert consultation, and a pre-survey. Convenience sampling was employed to select 320 patients with chronic skin wounds hospitalized at Chongming Hospital, Shanghai University of Medicine and Health Sciences and Qingdao Municipal Hospital from June 2023 to December 2024 for formal investigation, conducting scale reliability and validity analysis. The critical ratio method and correlation coefficient method were used for project analysis. Content validity of the scale was assessed using item-level content validity index and average scale-level content validity index, and construct validity was evaluated through exploratory factor analysis and confirmatory factor analysis. Reliability analysis employed Cronbach's α coefficient.Results:A total of 320 questionnaires were distributed, and 304 valid questionnaires were collected, with a valid response rate of 95.0%. The average scale-level content validity index was 0.91, and the item-level content validity index ranged from 0.80 to 1.00. Exploratory factor analysis revealed that the cumulative variance contribution rate of the five common factors was 67.483%. The overall Cronbach's α coefficient for the scale was 0.831. The final constructed scale comprised five dimensions of trajectory stage cognition, wound self-care skills, symptom management, psychosocial adaptation, and health information acquisition and resource utilization, with a total of 26 items.Conclusions:The Discharge Readiness Scale for Patients with Chronic Skin Wounds demonstrates good reliability and validity, providing clinical healthcare professionals with a standardized assessment tool.

Objective:To develop the Discharge Readiness Scale for Patients with Chronic Skin Wounds and evaluate its reliability and validity.Methods:The Discharge Readiness Scale for Patients with Chronic Skin Wounds was developed through literature review, semi-structured interviews, Delphi expert consultation, and a pre-survey. Convenience sampling was employed to select 320 patients with chronic skin wounds hospitalized at Chongming Hospital, Shanghai University of Medicine and Health Sciences and Qingdao Municipal Hospital from June 2023 to December 2024 for formal investigation, conducting scale reliability and validity analysis. The critical ratio method and correlation coefficient method were used for project analysis. Content validity of the scale was assessed using item-level content validity index and average scale-level content validity index, and construct validity was evaluated through exploratory factor analysis and confirmatory factor analysis. Reliability analysis employed Cronbach's α coefficient.Results:A total of 320 questionnaires were distributed, and 304 valid questionnaires were collected, with a valid response rate of 95.0%. The average scale-level content validity index was 0.91, and the item-level content validity index ranged from 0.80 to 1.00. Exploratory factor analysis revealed that the cumulative variance contribution rate of the five common factors was 67.483%. The overall Cronbach's α coefficient for the scale was 0.831. The final constructed scale comprised five dimensions of trajectory stage cognition, wound self-care skills, symptom management, psychosocial adaptation, and health information acquisition and resource utilization, with a total of 26 items.Conclusions:The Discharge Readiness Scale for Patients with Chronic Skin Wounds demonstrates good reliability and validity, providing clinical healthcare professionals with a standardized assessment tool.

Objective:To investigate the effect of GBP3 on replication of adult T-lymphocytic leukemia virus type 1(HTLV-1).Methods:Expression of GBP3 in HTLV-1-infected HeLa cell and THP1 cell was detected by Western blot.The knock-down efficiency of siRNAs targeting GBP3 in HeLa and THP1 cells was evaluated by Western blot.Effects of GBP3 overexpression or knockdown on expression of HTLV-1 proviral transcripts Tax,px,HBZ,Gag,ENV,5'UTR,and viral proteins Tax,p19 were investigated by RT-qPCR and Western blot.GTPase-defective mutant of GBP3,GBP3K51A was constructed to explore whether the effects of GBP3 on HTLV-1 infection were dependent on its GTPase activity.Results:GBP3 expression was upregulated in HTLV-1 infected HeLa and THP1 cells.GBP3 overexpression decreased expression of HTLV-1 proviral transcripts and viral proteins,whereas the knockdown of GBP3 has the opposite effects.Overexpression of GBP3K51A increased expression of HTLV-1 proviral transcripts and viral proteins.Conclusion:HTLV-1 virus infection can induce expression of GBP3;overexpression of GBP3 inhibits virus replication and may depend on GTPase.

Precision therapy has become an important approach in modern medicine,with the goal of providing individualized treatment according to the characteristics of individual patients.The successful development of precision medicine depends on the application of preclinical cancer models.Patient-derived organoid(PDO)xenograft models display characteristics of both PDO models and in vivo patient-derived tumor xenograft models.This type of model can not only maintain the heterogeneity of the original tumor,but also has additional advantages,such as large-scale cultivation,high-throughput drug screening in vitro and drug sensitivity testing in vivo.It is an innovative,precise preclinical disease model.In this review,we summarize the basic characteristics of the PDO xenograft model,analyze its construction method and influencing factors,further discuss its application in precision therapy,with the aim of providing a reliable preclinical experimental tool for individualized cancer treatment.

BACKGROUND:The patient underwent multiple hypoproteinemia after total hip arthroplasty,which affected postoperative healing and rehabilitation.OBJECTIVE:To investigate and screen the risk factors for hypoproteinemia after total hip arthroplasty,and to establish a nomogram prediction model so as to provide guidance for judging whether hypoproteinemia occurs after total hip arthroplasty.METHODS:A total of 355 patients who underwent total hip arthroplasty were included,and according to whether hypoproteinemia occurred on the first day after surgery,they were divided into 238 cases in the hypoproteinemia group and 117 cases in the normal group,with a hypoproteinemia rate of 67％.Data were collected,including age,gender,diabetes mellitus,hypertension,hyperuricemia,hyperlipidemia,anesthesia method,preoperative leukocytes,preoperative erythrocytes,preoperative hemoglobin,preoperative platelets,preoperative plasma prothrombin time,preoperative activated partial prothrombin time,preoperative international normalized ratio,preoperative thrombin time,preoperative fibrinogen,preoperative erythrocyte sedimentation rate,preoperative C-reactive protein,preoperative D-dimer,preoperative mean corpuscular hemoglobin content,preoperative mean corpuscular volume,operation time,body mass index,preoperative procalcitonin,and preoperative hematocrit.SPSS 27.0 software was used for univariate analysis,followed by R language(4.3.1)to perform least absolute shrinkage and selection operator regression and 10-fold cross-validation of the observation indicators to obtain the intersection of the two risk factors.SPSS 27.0 software was used to perform multivariate binary logistic regression to obtain the final risk factors.The prediction model of hypoproteinemia after total hip arthroplasty was constructed by R language.The receiver operating characteristic curve,calibration curve,and clinical decision curve were constructed to assess the predictive model predictive ability.RESULTS AND CONCLUSION:(1)Univariate analysis,least absolute shrinkage and selection operator regression,and multivariate logistic regression were used to screen out significant differences in age(OR=1.024,P=0.023),preoperative platelets(OR=0.995,P=0.028),and preoperative erythrocyte sedimentation rate(OR=1.031,P=0.045)in judging whether hypoproteinemia would occur after surgery(P＜0.05).(2)The nomogram prediction model was constructed based on the final risk factors screened by multivariate Logistic regression,and the prediction ability of the model was evaluated by constructing the receiver operating characteristic curve,and the area under the calculated receiver operating characteristic curve reached 0.835(95％CI=0.779-0.891),C-index=0.835.A threshold of 0-0.83 could bring better clinical efficacy calculated by the decision curve analysis.The model has good sensitivity and accuracy,which can better identify the risk of postoperative hypoproteinemia for medical staff and patients before total hip arthroplasty.

Objective:The current study aimed to evaluate the possible protective effects of N-acetylcysteine (NAC) against Indum-tin oxide (ITO) nanoparticle (Nano-ITO) -induced pulmonary alveolar proteinosis (PAP) in rats, especially via modulation of nuclear factor kappa B (NF-κB) signaling.Methods:In October 2019, 50 adult male Sprague-Dawley rats were randomly allocated into five groups (10 rats each) as follows: blank control group, saline control group, NAC control group (200 mg/kg), Nano-ITO group (receiving a repeated intratracheal dose of 6 mg/kg Nano-ITO) and NAC intervention group (pre-treated intraperitoneally with 200 mg/kg NAC 1.5 h before the administration of an intratracheal dose of 6 mg/kg Nano-ITO). The rats were exposed twice a week for 12 weeks. Rats were then euthanized under anesthesia, and their lungs were removed for histopathological and immunohistochemical analysis. The comparison of indicators reflecting oxidative stress and pulmonary inflammation among groups was conducted using one-way analysis of variance (ANOVA) and Bonferroni's test. The effect of NAC on Nano-ITO induced NF-κB signaling pathway in rats was analyzed.Results:Histopathological examination of Nano-ITO exposed rats revealed diffuse alveolar damage, including PAP, cholesterol crystals, alveolar fibrosis, pulmonary fibrosis, and alveolar emphysema. Immunohistochemical results of Nano-ITO exposed rats showed strong positive for nuclear factor κB p65 (NF-κB p65) and nuclear factor Kappa B inhibitory factor kinase (IKK-β) and weak positive for nuclear factor κB inhibitory protein α (IκB-α) in the nuclei of bronchiolar and alveolar epithelial cells. Compared with blank control group, saline control group and NAC control group, the level of total protein (TP) in bronchoalveolar lavage fluid of rats in Nano-ITO group was significantly increased ( P<0.05), and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) were significantly increased ( P<0.05), the levels of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were significantly increased ( P<0.05), and the levels of NF-κB p65, IKK-β, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in lung tissue were significantly increased ( P<0.05). Compared with Nano-ITO group, the levels of TP, T-AOC, MDA and TNF-α in bronchoalveolar lavage fluid of rats in NAC intervention group were significantly decreased ( P<0.05), and the levels of NF-κB p65 and ROS in lung tissue were significantly decreased (P<0.05). Western blot results showed that compared with the control groups, the protein expressions of NF-κB p65 and IKK-β in the lung tissue of Nano-ITO group were increased, while the protein expression of IκB-α was decreased ( P<0.05). Compared with Nano-ITO group, the protein expressions of NF-κB p65 and IKK-β in lung tissue of rats in NAC intervention group were decreased, while the protein expression of IκB-α was increased ( P<0.05) . Conclusion:The study demonstrated that Nano-ITO might induce pulmonary toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the pulmonary toxicity of Nano-ITO by inhibiting the NF-κB signaling pathway.

Objective:The current study aimed to evaluate the possible protective effects of N-acetylcysteine (NAC) against Indum-tin oxide (ITO) nanoparticle (Nano-ITO) -induced pulmonary alveolar proteinosis (PAP) in rats, especially via modulation of nuclear factor kappa B (NF-κB) signaling.Methods:In October 2019, 50 adult male Sprague-Dawley rats were randomly allocated into five groups (10 rats each) as follows: blank control group, saline control group, NAC control group (200 mg/kg), Nano-ITO group (receiving a repeated intratracheal dose of 6 mg/kg Nano-ITO) and NAC intervention group (pre-treated intraperitoneally with 200 mg/kg NAC 1.5 h before the administration of an intratracheal dose of 6 mg/kg Nano-ITO). The rats were exposed twice a week for 12 weeks. Rats were then euthanized under anesthesia, and their lungs were removed for histopathological and immunohistochemical analysis. The comparison of indicators reflecting oxidative stress and pulmonary inflammation among groups was conducted using one-way analysis of variance (ANOVA) and Bonferroni's test. The effect of NAC on Nano-ITO induced NF-κB signaling pathway in rats was analyzed.Results:Histopathological examination of Nano-ITO exposed rats revealed diffuse alveolar damage, including PAP, cholesterol crystals, alveolar fibrosis, pulmonary fibrosis, and alveolar emphysema. Immunohistochemical results of Nano-ITO exposed rats showed strong positive for nuclear factor κB p65 (NF-κB p65) and nuclear factor Kappa B inhibitory factor kinase (IKK-β) and weak positive for nuclear factor κB inhibitory protein α (IκB-α) in the nuclei of bronchiolar and alveolar epithelial cells. Compared with blank control group, saline control group and NAC control group, the level of total protein (TP) in bronchoalveolar lavage fluid of rats in Nano-ITO group was significantly increased ( P<0.05), and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) were significantly increased ( P<0.05), the levels of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were significantly increased ( P<0.05), and the levels of NF-κB p65, IKK-β, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in lung tissue were significantly increased ( P<0.05). Compared with Nano-ITO group, the levels of TP, T-AOC, MDA and TNF-α in bronchoalveolar lavage fluid of rats in NAC intervention group were significantly decreased ( P<0.05), and the levels of NF-κB p65 and ROS in lung tissue were significantly decreased (P<0.05). Western blot results showed that compared with the control groups, the protein expressions of NF-κB p65 and IKK-β in the lung tissue of Nano-ITO group were increased, while the protein expression of IκB-α was decreased ( P<0.05). Compared with Nano-ITO group, the protein expressions of NF-κB p65 and IKK-β in lung tissue of rats in NAC intervention group were decreased, while the protein expression of IκB-α was increased ( P<0.05) . Conclusion:The study demonstrated that Nano-ITO might induce pulmonary toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the pulmonary toxicity of Nano-ITO by inhibiting the NF-κB signaling pathway.