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 and compare the image quality and radiation dose between the spiral scanning and the axial scanning for skull phantom based on specific conditions.Methods:The position of the orbitomeatal base line(OBL)of the skull phantom was marked,and the different angles of elevation of skull were adjusted.The angles between OBL and bed surface were respectively set as 90°,100°,110° and 120°.The axial scanning and spiral scanning were respective adopted to conduct 24 times of image acquisition when the computed tomography dose index(CTDIvol)of fixed volume were respectively 40,50 and 60 mGy.The cross section of axial scanning was vertical to OBL,and the images of spiral scanning used the reconstructed technique of image quality enhancement(IQE)of removing spiral artifacts to conduct reconstruction along the OBL direction.The CT value(HU)and standard deviation(SD)of the bilateral cerebellum,temporal lobe,frontal lobe and parietal lobe of the phantom were measured,and the signal-to-noise ratio(SNR)of each lobe of the phantom was calculated.The CTDIvol and dose-length product(DLP)were recorded,and the effective dose(ED)of lens was calculated.Results:The differences of the SNR values of cerebellum and occipital lobe(R),cerebellum and occipital lobe(L),temporal lobe(R),temporal lobe(L),frontal lobe(R),frontal lobe(L),parietal lobe(R)and parietal lobe(L)between two kinds of scanning models were significant(F=6.48,5.83,7.00,6.20,7.30,8.26,5.72,5.83,P<0.05),respectively.There was significant difference in lens DLP between the two kinds of scanning models(F=10.96,P<0.05).The spiral scanning and IQE reconstructed technique were used to conduct image acquisition and processing.The SNR value of spiral scanning imaging was better than that of axial scanning,and the reconstructions of coronal and sagittal positions could be conducted,and the radiation doses of lens were similar,but the DLP value of spiral scanning was slightly higher than that of axial scanning at the same CTDIvol.Conclusion:Using the IQE reconstruction technique of spiral scanning can obtain satisfactory CT sectional images of skull under the situations that machine cannot change scanning angle or the scanning of axial position is unable to conduct cooperation.

Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Basal Forebrain ; Cholinergic Agents ; Cholinergic Neurons ; Humans ; Receptors, Histamine H1 ; Schizophrenia

Objective:To evaluate the clinical efficacy and safety of a skin care ointment containing oligomeric maltose X in the adjuvant treatment of eczema-related pruritus.Methods:A multicenter, randomized, double-blind, vehicle-controlled clinical study was conducted. From March to September 2021, outpatients with mild to moderate eczema were collected from departments of dermatology of 4 hospitals, including Beijing Friendship Hospital, Hebei Traditional Chinese Medical Hospital, the Third People′s Hospital of Hubei Province, and Taizhou Central Hospital in Zhejiang Province. The patients were randomly divided into two groups by using a random number table: observation group topically treated with a skin care ointment containing oligomeric maltose X, and vehicle control group topically treated with an ointment vehicle. The ointments were applied during the attacks of itching for 14 consecutive days. Visits were scheduled before, 7, and 14 days after the start of the adjuvant treatment. The efficacy was evaluated according to the eczema area and severity index (EASI) and visual analog scale (VAS) , and adverse events were recorded. The efficacy and safety analyses were conducted by using chi-square test and t test. Results:Totally, 232 patients with eczema were enrolled, including 90 males and 142 females, with the age being 40.13 ± 13.36 years; 156 patients were in the observation group, and 76 in the vehicle control group. Before the adjuvant treatment, there were no significant differences in EASI (2.07 ± 2.24 points vs. 2.29 ± 2.28 points) or VAS (6.22 ± 1.78 points vs. 6.20 ± 1.79 points) scores between the observation group and vehicle control group ( t = -0.70, 0.06, P = 0.486, 0.955, respectively) . After one-day treatment, the VAS scores significantly decreased compared with the baseline scores in the two groups ( P < 0.001, P = 0.003, respectively) . After 14-day treatment, the VAS score was significantly lower in the observation group (2.67 points) than in the vehicle control group (3.35 points; t = -2.28, P = 0.024) . After 7- and 14-day treatment, the EASI scores significantly decreased compared with the baseline scores in both the two groups (all P < 0.001) , but there were no significant differences between the two groups ( P = 0.853, 0.731) . No adjuvant treatment-related adverse events were recorded in either of the two groups. Conclusion:The skin care ointment containing oligomeric maltose X is safe and effective in the adjuvant treatment of eczema-related pruritus, and can be applied to clinical practice.

Objective:To investigate the predictive value of matrix metalloproteinase-9 (MMP-9) and neutrophil to lymphocyte ratio (NLR) in delayed perihematomal edema (dPHE) after spontaneous intracerebral hemorrhage (sICH).Methods:Patients with sICH admitted to Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School within 24 h of onset from January 2018 to June 2020 were enrolled retrospectively. Serum MMP-9 levels and peripheral blood cell counts were detected, and NLR were calculated within 24 h of onset. dPHE was defined as an increase of 3 ml in absolute edema volume at 10-21 d after onset of sICH compared with that at 5-9 d. The demographic and baseline clinical and imaging data of the dPHE group and the non-dPHE group were compared. Multivariate logistic regression analysis was used to identify the independent predictors of dPHE. The receiver operating characteristic (ROC) curve was used to evaluate the predictive values of MMP-9 and NLR for dPHE. Results:A total of 195 patients with sICH (61.88±10.60 years old) were enrolled in the study. One hundred and forty-eight patients were males (75.9%). There were 53 patients (27.2%) in the dPHE group and 142 (72.8%) in the non-dPHE group. Univariate analysis showed that age, baseline hematoma volume, baseline National Institutes of Health Stroke Scale score, fasting blood glucose, high-sensitivity C-reactive protein, MMP-9, neutrophil count, NLR and the proportion of irregular hematoma in the dPHE group were significantly higher than those in the non-dPHE group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for confounding factors, higher MMP-9 (odds ratio [ OR] 4.291, 95% confidence interval [ CI] 2.041-6.590; P=0.007) and higher NLR ( OR 2.530, 95% CI 1.157-4.022; P=0.011) were all the independent predictors of dPHE. ROC curve analysis showed that the area under the curve of MMP-9 for predicting dPHE was 0.819 (95% CI 0.756-0.884; P<0.001), the optimal cut-off value was 164.0 μg/L, and the sensitivity and specificity were 86.79% and 66.90% respectively. The area under the curve of NLR for predicting dPHE was 0.788 (95% CI 0.719-0.856; P<0.001), the optimal cut-off value was 5.683, and the corresponding sensitivity and specificity were 77.36% and 71.13% respectively. Conclusions:sICH patients with higher baseline MMP-9 and NLR are more likely to develop dPHE. Early detection of MMP-9 and NLR in peripheral blood after admission can predict dPHE.

Objective:To provide reference for the development of a more intelligent and systematic nursing clinical decision support system based on the concept of precision nursing and data sharing, the nursing plan module of clinical decision support system.Methods:An evidence-based knowledge base was constructed based on the nursing process and the standardized nursing terminologies; the nursing plan module was designed according to clinical needs, and the logical reasoning rules were formulated from the generation, sequencing and stopping of nursing problems, objectives, measures and activities, and finally the nursing plan module of clinical decision support system was formed.Results:The nursing plan module of clinical decision support system included the basic information of patients, positive evaluation items and weight values, nursing problems, objectives, measures and activities, etc. the module could automatically deduce the nursing plan according to the patient's individual characteristic index (positive evaluation item), and sort the nursing problems and corresponding measures and activities according to the generation time, weight value and correlation degree. It could automatically distinguish nursing problems, goals, measures and the time of activity stop, and realize intelligent decision-making.Conclusion:The interface of nursing plan module of this system is clear and logical reasoning rules are rigorous. It breaks through the bottleneck of nursing decision-making based on personal professional knowledge and experience in clinical situation for a long time, which can ensure the homogeneity of nursing plan and improve the correctness of decision-making.

Objective:To investigate the value of renal glucose threshold and related factors in patients with type 2 diabetes mellitus.Methods:According to the cut-off point of normal renal glucose threshold(RT G 8.9-10 mmol/L), 107 patients with type 2 diabetes mellitus hospitalized in the Endocrinology Department of our hospital were divided into three groups: high RT G group(RT G>10 mmol/L), medium RT G group(8.9 mmol/L≤RT G≤10 mmol/L), and low RT G group(RT G<8.9 mmol/L). The clinical data and biochemical characteristics of each group were collected and analyzed. Results:The proportions of patients with high, medium, and low RT G of type 2 diabetes mellitus were 56%, 29%, and 15%, respectively. There were significant differences in RT G value, age, course of disease, body mass index(BMI), fasting plasma glucose(FPG), HbA 1C, total cholesterol(TC), serum creatinine, mean blood glucose(MBG), and 24-hour urine glucose between high and medium RT G groups. RT G, gender, BMI, FPG, HbA 1C, TC, and MBG in patients with high RT G group were different from those in low RT G group. Only RT G revealed a difference between medium and low RT G groups. Correlation analysis showed that RT G was positively correlated with gender, age, BMI, HbA 1C, TC, and low density lipoprotein-cholesterol(LDL-C). Regression analysis showed that BMI, HbA 1C, and LDL-C were the related factors affecting the RT G of patients with type 2 diabetes. Conclusion:There is a larger proportion of patients with high RT G in type 2 diabetes mellitus. Their BMI, HbA 1C, and LDL-C are associated with RT G in the patients with type 2 diabetes mellitus.

Objective:To investigate the effect of serum lipid level on prognosis of patients with small cell lung cancer (SCLC) at the initial treatment.Methods:The clinical data of patients with SCLC from 2012 to 2017 in our hospital were retrospectively analyzed. According to the standard of appropriate level and abnormal stratification of blood lipid in Chinese population, the lipids included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDLC) at the time of initial treatment were grouped. Then the relationship between different lipid levels and clinicopathological characteristics was analyzed. Finally, Cox proportional hazard model was used to analyze the independent prognostic factors of patients.Results:A total of 129 patients with SCLC were included in this study. At the time of initial treatment, there were 90 (69.8%) cases whose TC < 5.2 mmol/L, while 39 (30.2%) cases ≥5.2 mmol/L; 95 (73.6%) cases whose TG <1.7 mmol/L, while 34 (26.4%) cases ≥1.7 mmol/L; 27 (20.9%) cases whose HDLC <1.0 mmol/L while 102 cases (79.1%) ≥1.0 mmol/L; 90 (69.8%) cases whose LDLC <3.4 mmol/L while 39 cases (30.2%) ≥3.4 mmol/L. The patients′ triglyceride initial treatment was associated with their body mass index ( P<0.05). The median disease-free survival (PFS) of SCLC patients was related with their serum TC level and clinical stage ( P<0.05) and the overall survival (OS) was related with clinical stage of SCLC patients ( P<0.05). The median PFS of SCLC patients in the TC <1.7 mmol/L group at the initial treatment was 10.5 months, significantly longer than 8.8 months of the TC ≥1.7 mmol/L group ( P=0.024). The median OS of SCLC patients in the TG <1.7 mmol/L group at the initial treatment was 20.2 months, marginally longer than 15.6 months of the TG ≥1.7 mmol/L group ( P=0.097). Multivariate analysis result showed that, the TG level was an independent risk factor of SCLC progression at the time of initial treatment ( P=0.024). There was no significant correlation of TC, HDLC, LDLC and SCLC prognosis ( P>0.05). Conclusion:TG level is an independent risk factor for the progression of SCLC at the time of initial treatment, and the increase of TG level indicates rapid disease progression and poor prognosis.