The liver is the largest visceral organ in the human body, responsible for multiple important functions such as metabolism, detoxification, nutrient storage, and immune regulation. Hepatocytes located along the portal-central vein axis have heterogeneity in gene expression and function, which led to the concept of liver zonation. Cells in different regions play different roles in metabolic processes, and the coordination and cooperation between these cells are crucial for maintaining normal liver function. In recent years, the advancements in single-cell genomics and spatial transcriptomics technologies have significantly improved our understanding of liver zonation. This article summarizes the important role of metabolic zonation in maintaining liver function and its relationship with disease and aging, providing a theoretical basis for further research and therapeutic strategies.

The liver is the largest visceral organ in the human body, responsible for multiple important functions such as metabolism, detoxification, nutrient storage, and immune regulation. Hepatocytes located along the portal-central vein axis have heterogeneity in gene expression and function, which led to the concept of liver zonation. Cells in different regions play different roles in metabolic processes, and the coordination and cooperation between these cells are crucial for maintaining normal liver function. In recent years, the advancements in single-cell genomics and spatial transcriptomics technologies have significantly improved our understanding of liver zonation. This article summarizes the important role of metabolic zonation in maintaining liver function and its relationship with disease and aging, providing a theoretical basis for further research and therapeutic strategies.

As one of the most common solid organ malignant tumors in the world,hepatocellular carcinoma has climbed to the fourth place in incidence rate and the second place in mortality in China,which seriously threatens people's health.Terpenoids are natural active substances widely present in nature,among which sesquiterpenoids are numerous.They exhibit a variety of pharmacological activities,such as anti-tumor,antibacterial,anti-inflammatory,antiviral and antioxidant activities.This article reviews the research progress on the anti-hepatocellular carcinoma mechanism of sesquiterpenes from 2015 to 2024.The results showed that 24 sesquiterpenoids for the treatment of hepatocellular carcinoma have been reported in the literature in the past 10 years,and these compounds have shown potential in treating hepatocellular carcinoma by inhibiting cancer cell proliferation,inducing apoptosis,preventing invasion and metastasis,regulating immunity,and enhancing anti-drug resistance.The mechanism of anti-hepatocellular carcinoma mainly involves three regulatory pathways:phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,nuclear factor kappa-B signaling pathway,and mitochondrial pathway.In the future,it is necessary to continue to explore new anti-hepatocellular carcinoma drugs with high research value,conduct in-depth analysis on the mechanism of synergistic anti-hepatocellular cancer effects of multiple components,targets,pathways,and accelerate the development of finished products in order to be widely used in clinical practice.

Objective:To establish the long-term trajectories of lung function in children with bronchial asthma (asthma) and explore the risk factors of persistent pulmonary dysfunction.Methods:A retrospective cohort study was conducted.Children with asthma aged above 14 years who had been followed up regularly and completed pulmonary function testing in Children′s Hospital of Capital Institute of Pediatrics were enrolled in the study from January to December 2019.Their lung function data and clinical information were collected.The latent class growth model (LCGM) was used to fit the change of lung function in children with asthma, and different trajectory groups were established.Comparison between groups was performed by t-test, ANOVA or Chi- square test.The risk factors for the lung function trajectory were analyzed by the multivariate Logistic regression method. Results:A total of 173 children with asthma, aged from 6 to 17, were enrolled, and 1 160 lung function tests were completed.Four forced expiratory volume in the first second/forced vital capacity (FEV 1/FVC) latent class trajectory groups were established, including persistent high level [27 cases (15.6%)], above average level [66 cases (38.1%)], below average level [66 cases (38.1%)], and persistent low level [14 cases (8.1%)]. In all the 4 different trajectory groups, the FEV 1/FVC values were significantly different among patients of different ages (all P<0.05). The FEV 1/FVC values of patients at all ages in the persistent high level group were above 90%.The FEV 1/FVC values of patients in other 3 level groups decreased as a whole as the age increased.FEV 1/FVC of patients in the persistent low level group decreased to below 80% when they entered the school age period and approached 70% in adolescence.The trajectory and fluctuation of maximal midexpiratory flow (MMEF), which represents the small airway function, were similar to those of FEV 1/FVC.Risk factor analysis showed that the risk of lung function decreasing below the average level in children with typical asthma was 11.940 times higher than that in children with cough variant asthma ( P=0.008). The risk of lung function deteriorating to below the average level in children with multiple allergen sensitivities was 7.462 times higher than that in children with single allergen sensitivity ( P=0.015). Children taking drugs irregularly were 6.337 times more likely to suffer persistent low lung function than children taking drugs regularly ( P=0.035). Boys were 6.186 times more likely to suffer a lung function reduction to below the average level than girls ( P=0.002). Conclusions:Four long-term trajectories of lung function in asthmatic children aged 6 to 17 years can be established: persistent high level, above average level, below average level and persistent low level.The long-term lung function of nearly a half of the asthmatic children is below the average level.Many children develop persistent airflow limitation in adolescence, and few at school age.Typical asthma, multiple allergen sensitivities, irregular medication and boy were the risk factors of long-term lung function reduction.

Objective: To explore the cutoff value of FEV₁/FVC for evaluating obstructive ventilation dysfunction in children. Methods: Three hundred and eighty-three healthy children (190 boys and 193 girls) aged 6-14 years in primary and middle school in Beijing, who were enrolled from May 2010 to June 2011, had their spirometry done with the Jaeger lung function instrument, and the lower limit of normal (LLN) of FEV₁/FVC was calculated. Two hundred and thirteen asthmatic children (151 boys and 62 girls) aged 6-14 years from the outpatient Department of Allergy, Capital Institute of Pediatrics were enrolled consecutively from June to July 2018, whose clinical history and pulmonary function parameters were collected. The expected value of spirometric parameters of asthmatic children was calculated according to Zapletal prediction equations. And the LLN of FEV₁/FVC in healthy children was used as the gold standard to calculate the sensitivity, specificity, Youden index and Kappa value of FEV₁/FVC<80% and FEV₁/FVC< 92% predicted. Results: In healthy children, the FEV₁/FVC and the LLN were 91%±5% and 82% respectively, while 90%±6% and 81% in boys, and 92%±5% and 84% in girls. There were 27 (12.7%) asthmatic children whose FEV₁/FVC<80% but FEV₁/FVC≥92% predicted (χ²=123.7, P<0.01). The sensitivity, specificity, Youden index and Kappa value of FEV₁/FVC<80% were 80.3%, 100%, 0.803 and 0.787 respectively when FEV₁/FVC<80% was used as the criteria to assess lung function, while they were 57.3%, 100%, 0.573 and 0.547, respectively, when FEV₁/FVC<92% predicted was used as criteria. Conclusions The 80% of FEV₁/FVC has a better consistency with the LLN of FEV₁/FVC than 92% of FEV₁/FVC% predicted. It is more accarate to use FEV₁/FVC<80% as the diagnostic criteria for airway obstruction.

Objective:To evaluate the oncologic outcomes of different laparoscopic radical hysterectomy.Methods:From January 2011 to December 2014, the laparoscopic operation cases of cervical cancer at stage Ⅰb1, Ⅰb2, Ⅱa1 and Ⅱa2, including the histologic subtypes of squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma, were collected in five clinical centers. The data were divided into two groups according to the surgical procedures, that is, modified laparoscopic-vaginal radical hysterectomy (mLVRH) and total laparoscopic radical hysterectomy (TLRH). The overall survival rate (OS), disease-free survival rate (DFS) at 5 years were retrospectively analyzed in this study.Results:There were 674 cases in total, including 377 cases of mLVRH, 297 cases of TLRH. (1) The OS at 5 years: the mLVRH was 96.1% and the TLRH was 92.0%, and the mLVRH was higher than that of TLRH （ P=0.010）. Stratify analysis， including stage of disease （Ⅰb1 and Ⅱa1）， histologic subtypes （squamous-cell carcinoma, adenocarcinoma）， lymph node metastasis， revealed that, ① Stage of disease: in stage Ⅰb1, the OS at five years of mLVRH was higher than that in TLRH group （98.6% vs 93.6%, P=0.012）. In stage Ⅱa1, there was significant difference between the two groups, the OS at five years of mLVRH and TLRH were 93.6% and 77.6% （ P=0.007）. ② Histologic subtypes: for the OS at five years of squamous-cell carcinoma, mLVRH and TLRH were 96.1% and 92.3%, and there was significant difference （ P=0.046）； for adenocarcinoma, the OS at five years were 91.0% and 88.6%， and there was no difference between two groups （ P=0.230）. ③ Lymph node metastasis： the mLVRH and TLRH with lymph node metastasis, the OS at five years were 98.6% and 96.4%; the mLVRH and TLRH without lymph node metastasis, the OS at five years were 89.3% and 80.8%. There were no significant differences between the two groups,respectively ( P=0.156， P=0.093）. (2) The DFS at 5 years: there was no significant difference between mLVRH and TLRH (94.1% vs 90.9%, P=0.220). Stratify analysis for stage of disease, the mLVRH group was higher than that in the TLRH group in stage Ⅰb1 (97.0% vs 92.8%, P=0.039). However, for stage Ⅱa1, there was no significant difference between mLVRH and TLRH group （88.2% vs 75.8%, P=0.074）. Conclusions:The results of this retrospective study indicated that different laparoscopy surgical procedures had diverse oncologic outcomes. The OS at 5 years of the mLVRH is superior to the TLRH. The DFS at 5 years in Ⅰb1 stage, the mLVRH is higher than the TLRH. Therefore, the modified laparoscopy is still an alternative surgery for early cervical cancer patients when following the principle of no-tumor-exposure.

Objective To determine the expression of miRNA-148a-3p in CD4+ T lymphocytes in peripheral blood of patients with psoriasis vulgaris,and to explore its role in occurrence of psoriasis vulgaris.Methods Totally,20 patients with psoriasis vulgaris and 20 healthy controls were enrolled from Guangzhou Institute of Dermatology between July 2017 and April 2018.Peripheral venous blood samples were obtained from these subjects,and CD4+ T lymphocytes were isolated from these peripheral blood samples by magnetic cell sorting system.Real-time quantitative PCR (RT-PCR) was performed to determine the expression of miRNA-148a-3p in CD4+ T lymphocytes in the peripheral blood.Potential target genes of miRNA-148a were predicted by using bioinformatics software,and verified by using a dual-luciferase reporter system.Western blot analysis was conducted to determine the protein expression of Bcl-2 interacting mediator of cell death (Bim,the potential target gene of miRNA-148a-3p) in the CD4+ T lymphocytes of the subjects.Statistical analysis was carried out with SPSS 20 software by two sample-t test for comparing the means of normally distributed data,and by Pearson correlation analysis for analyzing the correlation of two variables.If the data were not normally distributed,Mann Whitney U test was used for comparing means between two groups,and Spearman correlation analysis for analyzing the correlation of two variables.Results The miRNA-148a-3p expression in the CD4+ T lymphocytesin the psoriasis vulgaris group (18 cases,5.61 ± 1.66) was significantly higher than that in the healthy control group (12 cases,1.00 ± 0.26;U =12,P ＜ 0.05),and was positively correlated with the psoriasis area severity index (PASI) score (r =0.93,P ＜ 0.001).Bim was predicted to be one of the potential target genes of miRNA-148a-3p by bioinformatics software,which was also verified by using a dual-luciferase reporter system.The protein expression of Bim in the CD4 + T lymphocytes was significantly lower in the psoriasis vulgaris group (11 cases,0.69 ± 0.07) than in the healthy control group (8 cases,0.93 ± 0.06;t =4.38,P ＜ 0.01),and the protein expression of Bim in the patients with psoriasis vulgaris was negatively correlated with PASI score (r =-0.774,P ＜ 0.01).Conclusion miRNA-148a-3p is overexpressed in CD4+ T cells in the peripheral blood of patients with psoriasis vulgaris,which may regulate the protein expression of Bim,leading to abnormal activation of CD4+ T cells,and then participate in the occurrence and development of psoriasis.

In order to obtain the bifunctional chimeric molecule of single-chain urokinase-type plasminogen activator (scu-PA) which can inhibit platelet aggregation, PRGDWR peptide was inserted into the site between Gly 118 and Leu119 (called insertion mutant B, InB). The recombinant gene of InB was expressed by Pichia pastoris. The secreted protein was purified by metal chelate affinity and strong cation exchange chromatography. The amidolytic ability of mutant InB is 5 900 IU/mg, the kinetic constants is: KInB m,plg=56.8 μmol*L-1，kInBcat,plg=0.33 s- 1. The kinetic constants of plasminogen activation reaction is: KInB m,plg=0.397 μmol*L-1，kInBcat,plg=0.0164 s-1. Fibrin inhibit the catalytiv ability of InB during plasminogen activatio n, the influence factor is 0.463(means InB remain 46.3% of the catalytic abili ty when fibrin was involved in the reaction system). The mutant not only has alm ost the same catalytic ability as wild type scu-PA, but also has strong ability of anti-platelet aggregation(compared with scu-PA), IC50 of InB is 12.7 μmol*L-1.

Because the influence of fibrin on the reaction of plasm inogen activation by various plasminogen activators is different, the kinetic co nstant of the reaction of plasminogen activation catalyzed by InB with and witho ut fibrin were detected. The result is: Kfibrinm＝4.2 μmol*L -1，greater than the normal Km=0.379 μmol*L-1; kfib rincat＝0.107 s-1，greater than the normal kcat=0.0165 s-1. The results suggest that existence of fibrin in the reaction system of plasminogen activation depress the affinity between InB and plasminog en, but accelerates the hydrolysis of plasminogen by InB. The count up effect is inhibition.