Liver fibrosis is a critical pathological stage in the progression of chronic liver diseases， involving the interaction between multiple mechanisms such as abnormal activation of hepatic stellate cells and extracellular matrix deposition. Since traditional animal models and two-dimensional cell culture systems cannot faithfully recapitulate the complex multicellular interactions and metabolic microenvironment of human liver fibrosis， three-dimensional liver organoid technologies have gradually been used in the construction of liver fibrosis models， providing novel research methods for mechanistic studies and therapeutic evaluation. Focusing on the construction of liver fibrosis-related organoid models， this article elaborates on the association of abnormal activation of hepatic stellate cells， chronic inflammatory response， gut-liver axis signaling， and lipid metabolic dysregulation with the progression of liver fibrosis and summarizes the current research advances in the application of organoid models for anti-fibrotic drug screening and targeted therapeutic assessment. Finally， this article briefly discusses the limitations of existing organoid models for liver fibrosis and future research directions， in order to provide a theoretical reference for both basic research and clinical application in liver fibrosis.

The etiology of tumors is complex and influenced by multiple factors, including the host and environmental conditions. Allergy is primarily driven by the immune response of helper T cell 2 (Th2). Research has shown that the Th2 immune response is closely related to tumors, which is specifically manifested through Th2 antibodies, allergy-related effector cells and mediators within the tumors, as well as tumor immune-related functions. This internal interaction mechanism will increase the complexity and challenges associated with the clinical diagnosis and treatment of tumors and allergy. The formation of allergic constitution is shaped by both congenital and acquired factors, and its physical state is closely linked to the occurrence and progression of allergic diseases. Therefore, this paper aims to explore the relationship between tumors and allergic reactions from the perspective of traditional Chinese medicine (TCM) constitution theory. Based on the four basic principles of the TCM constitution, including endowment inheritance theory, environment constraint theory, body-spirit composition theory, and life process theory, this exploration will focus on four aspects: genetic factors and internal disease causes, inflammatory environments and functional regulation, psychological disorders and emotional pathogenesis, as well as age structure and disease risk. Furthermore, from the perspective of constitution-disease relation of chronic disease prevention, this paper will discuss the significant importance of adjusting allergic constitution to improve both subjective symptoms and objective indicators of allergic reactions in tumor patients.

AIM: To investigate the changes of microRNA-34a(miR-34a)and microRNA-29b(miR-29b)levels in lens epithelial cells of age-related cataracts(ARC)patients and their clinical significance.METHODS: A total of 65 ARC patients(study group)and 53 cases of clear lens anterior capsulorhexis(control group)who visited our hospital from February 2023 to February 2024 were gathered. Pearson was applied to test the correlation between miR-34a and miR-29b. Multifactor Logistic regression was applied to determine the factors affecting the occurrence of ARC.RESULTS: Compared with the control group, the expression levels of miR-34a and miR-29b in lens epithelial cells of the research group showed a significant decrease trend(all P<0.05). There was a positive correlation between miR-34a and miR-29b in the lens epithelial cells of ARC patients(r=0.472, P<0.05). MiR-34a and miR-29b were influence factors for ARC(all P<0.05).CONCLUSION: The levels of miR-34a and miR-29b in lens epithelial cells of ARC patients are significantly reduced, which is associated with the occurrence of ARC.

Objective:To establish the reference range of red blood cell parameters within 24 hours after birth of premature infants with different gestational ages and genders.Methods:According to the inclusion criteria and exclusion criteria, a retrospective analysis was performed in premature infants who were admitted to the neonatal intensive care unit from January 1, 2018 to December 31, 2019. These newborns were delivered in the obstetrics department of our hospital or came from other parts of Jilin Province. All of their radial artery blood were collected within 24 hours after birth. According to the blood examination results, we analyzed reference range of red blood cell parameters of these premature infants.Results:With the increase of gestational age, the number of RBC, HGB, HCT, MCHC gradually increases and the number of MCV, MCH gradually decreases. There are differences in some red blood cell parameters of premature infants with 34 week≤gestational age<37 week between different genders. Compared with boys, the number of RBC, HGB, HCT and MCV in girls were higher. The number of RBC in premature infants with 23 week≤gestational age<28 week and 28 week ≤ gestion age<34 week are 2.58×10 12-5.45×10 12/L and 2.97×10 12-5.86×10 12/L respectively. In the group of premature infants with 34 week ≤gestion age<37 week, the number of RBC in boys is 3.38×10 12-5.83×10 12/L, while the number of RBC in girls is 3.18-5.89×10 12/L. There're no difference in RDW among preterm infants with different gestational ages and genders, which is 14.8%-20.6%. Conclusions:The study established the reference range of red blood cell parameters of 23 w≤gestational age<37 w premature infants within 24 hours after the birth and explored the differences in red blood cell parameters of premature infants with different gestational ages and genders.

Objective:To investigate the clinical efficacy and safety of gabapentin or topiramate combined with venlafaxine in the treatment of chronic migraine patients with generalized anxiety disorder.Methods:From June 2018 to February 2020, 127 patients with chronic migraine complicated with generalized anxiety disorder in the Second Affiliated Hospital of Guangxi Medical University were selected. The patients were divided into gabapentin combined with venlafaxine group (observation group, 64 cases) and topiramate combined with venlafaxine group (control group, 63 cases) according to the random number table method, and all patients were treated for 6 months. The headache attack days per month, headache visual analogue scale (VAS), migraine specific quality of life questionnaire V2.1 (MSQ V2.1), headache impact measurement-6 (HIT-6) score, Pittsburgh sleep quality index (PSQI) score were recorded before treatment and 3 and 6 months after treatment.Results:In observation group, 57 cases completed 3 months of treatment, and 53 cases completed 6 months of treatment. In the control group, 56 cases completed 3 months of treatment, and 50 cases completed 6 months of treatment. The headache attack days per month, headache VAS, HIT-6 and PSQI 3 and 6 months after treatment in 2 groups were significantly lower than those before treatment, observation group: (16.31 ± 5.02) and (15.69 ± 6.31) d vs. (22.62 ± 3.27) d, (3.67 ± 1.60) and (1.91±1.05) scores vs. (5.09 ± 1.43) scores, (49.34 ± 11.01) and (47.34 ± 9.05) scores vs. (60.25 ± 11.61) scores, (10.09 ± 2.81) and (9.68 ± 2.74) scores vs. (13.50 ± 2.81) scores; control group: (14.58 ± 7.37) and (9.92 ± 5.07) d vs. (23.05 ± 5.24) d, (4.74 ± 1.15) and (3.16 ± 1.60) scores vs. (5.90 ± 2.06) scores, (42.77 ± 8.02) and (40.09 ± 9.72) scores vs. (59.37 ± 9.08) scores, (9.66 ± 2.71) and (8.62 ± 2.07) scores vs. (14.61 ± 2.79) scores, and there were statistical differences ( P<0.05). The headache VAS 3 and 6 months after treatment in observation group was significantly lower than that in control group, and there was statistical difference ( P<0.05). The functional limitations, function loss, emotional function scores and total score of MSQ V2.1 3 and 6 months after treatment in 2 groups were significantly lower than those before treatment, observation group: (17.62 ± 9.81) and (16.01 ± 5.73) scores vs. (36.96 ± 9.55) scores, (12.17 ± 5.60) and (11.09 ± 3.27) scores vs. (17.06 ± 6.08) scores, (8.42 ± 2.17) and (8.94 ± 1.90) scores vs. (11.40 ± 4.09) scores, (33.24 ± 9.61) and (28.62 ± 5.04) scores vs. (62.75 ± 14.02) scores; control group: (17.08 ± 8.73) and (16.79 ± 5.19) scores vs. (36.82 ± 9.68) scores, (9.04 ± 4.48) and (8.90 ± 3.46) scores vs. (17.26 ±6.01) scores, (6.92 ± 2.61) and (5.15 ± 1.74) scores vs. (11.30 ± 5.47) scores, (31.65 ± 9.17) and (30.66 ± 6.04) scores vs. (62.91 ± 11.18) scores, and there were statistical differences ( P<0.05). There was no significant difference in the effective rate and the incidence of adverse drug reactions 3 and 6 months after treatment between 2 groups ( P>0.05). Conclusions:Gabapentin or topiramate combined with venlafaxine can reduce the degree of headache in chronic migraine patients with generalized anxiety disorder, reduce the number of headache days per month, improve sleep and improve the quality of life. However, the adverse reactions of gabapentin still need to be paid more attention.

Objective:To investigate the association of lipoprotein a (Lpa) in early pregnancy with gestational diabetes mellitus (GDM) risk.Methods:A total of 445 pregnant women in 12-14 gestational weeks from "Maternal Key Nutritional Factors and Offspring's Atopic Dermatitis" cohort were included in this study. The demographic characteristics of participants were collected by using questionnaires, and the fasting glucose and lipids levels in early pregnancy were measured. The results of oral glucose tolerance test (OGTT) between 24-28 gestational weeks were recorded. Multivariate logistic regression model was applied to analyze the association of Lpa with GDM by calculating the OR and 95% CI after adjustment for covariates. Results:The incidence number of GDM was 78 (17.5%). The Lpa level in pregnant women with GDM was significantly higher than that in pregnant women without GDM [105.5 (92.0, 122.0) vs. 97.0 (87.0, 109.0) mg/L], P<0.05. Lpa was significantly associated with GDM risk [ OR (95% CI) =1.21(1.08-1.36) per 10 mg/L], P<0.05. The association was still significant after adjustment for covariates including age, gestational weeks et al, the adjusted OR was 1.14 (95% CI: 1.01-1.30), P=0.03. Conclusions:The elevation of Lpa in early pregnancy is one of risk factor for GDM. Maintaining normal Lpa level during early pregnancy can benefit early prevention of GDM and offspring health.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective:To search for circulating complement-related proteins that predict hypertensive disorders of pregnancy (HDP) based on reports of the development of gestational hypertension and proteinuria and to investigate the role of the complement system in the development of HDP.Methods:A nested case-control study was used, the serum samples of pregnant women who had been given birth or cesarean section in Guangzhou Women and Children′s Medical Center from November 2014 to March 2017 were collected. A total of 60 HDP and 60 normal pregnant women were included and matched 1∶1 by age and gestational week. Unlabeled mass spectrometry was used to screen the differential expression of complement factors in serum samples of 12 pairs of HDP patients and normal pregnancy collected before 20 weeks of pregnancy, and another 48 pairs of serum samples of HDP patients and normal pregnant women were used for preliminary verification. It was selected when the fold change (FC) of complement factor expression was>1.2 or <0.8 and P<0.05. ROC curve was used to evaluate the diagnostic value of corresponding factors. Results:FC of serum C1s, C8 beta chain (C8β) and C1 inhibitor (C1-INH) of HDP patients were 1.19, 1.23, 0.73 ( t=2.07, 2.06, -3.40; P<0.05), respectively. FC of serum C1s, C8 β, C1-INH, factor H-related protein 5 (CFHR5), clusterin (CLU), and C-reactive protein (CRP) of PE patients were 1.39, 1.50, 0.72, 2.49,4.38, and 1.82 respectively ( t=4.36, 5.61, -3.70, 6.82, 8.70, 7.27; P<0.05).The AUC of combining C1s, C8 β and C1-INH was 0.89 in HDP. The AUC of CFHR5, CLU, and CRP in preeclampsia was 0.88, 0.92, and 0.91. Conclusions:Before HDP, the activation and regulation of classic complement pathway and alternative pathway were disordered in pregnant women. The combined detection of complement C1s, C8 β and C1-INH is expected to be used in the prediction of HDP, and CFHR5, CLU, and CRP are expected to be used in the prediction of preeclampsia.

Objective Find abnormal changes of plasma lipid metabolism-related proteins before 20 weeks of gestation in patients with hypertensive disorder of pregnancy(HDP), and preliminarily investigate the role of plasma apolipoprotein C4 elevation in HDP. Methods A nested case-control study was used. The plasma were collected from pregnant women who underwent routine prenatal examination in Guangzhou Women and Children's Medical Center from November 2014 to March 2017. Label-free mass spectrometry was used to detect the differences in plasma lipid metabolism-related proteins before 20 weeks of gestation between 12 pairs of HDP patients and normal controls, and different 48 pairs of samples were used for verification. The protein with the most significant difference multiples was screened to study its effects on monolayer permeability and nitric oxide secretion of endothelial cells. One-way ANOVA was used for comparison between groups, and P<0.05 was considered as statistically significant difference. Results Compared with the control, the lipid metabolism-related proteins, APOC4, Fatty acid-binding protein 4 (FABP4), Apolipoprotein E (APOE), Apolipoprotein C3 (APOC3) and Beta-2-glycoprotein 1(APOH) raised to 1.94, 1.82, 1.59, 1.55 and 1.38 times, phospholipid transfer protein (PLTP) decreased to 0.78 times in plasma before 20 weeks of pregnancy of patients with HDP (t value were 2.499, 2.497, 2.081, 2.098, 2.426 and 2.564, respectively, P<0.05). Cell experiments results showed that 50 ng / ml APOC4 significantly increased 20％ HUVEC single layer cell permeability to FITC-labeled dextran (F=455.4, P<0.01), and significantly decreased the level of nitric oxide in the supernatant of HUVEC culture by 25％ (F=61.92, P<0.01). Conclusions Before diagnosis, plasma protein levels involved in lipid metabolism in HDP patients have been changed, resulting in abnormal lipid metabolism. APOC4 can increase the permeability of vascular endothelial cells, inhibit endothelial source of NO secretion, cause endothelial dysfunction.

Objective To investigate the relationship between white matter lesions(WML) and cognitive impairment in migraine with and without aura.Methods 56 migraine without aura patients (MwoA group),22 migraine with aura patients(MA group) and 30 normal controls were recruited.All of them were performed head MRI examination and were evaluated by operational definitions of ARWMC and Mattis Dementia Ratiing Scale(DRS),and compare among three groups,discuss the relationship between WML and cognitive impairment.Results (1) Compared with control group,the occurrence rate of WML in MA group was significantly higher(40.9％ vs 13.3％,x2=22.74,P＜0.01).The OD-ARWMC score was significantly higher in both MA and MwoA groups((0.73±l.12) vs (0.13±0.35),t=2.76,P＜0.01;(0.36±0.67) vs (0.13±0.35),t=1.75,P＜0.05).Compared with MwoA group,the occurrence rate of WML and the OD-ARWMC score of MA group was significantly higher(t=22.80,P＜0.01;t=1.79,P＜0.05).(2) During the attack period,the DRS total scale and its 5 factors (attention,initiation/perseveration,concept formation,construction and memory) were significantly lower in both MwoA and MA group(P＜0.05 or 0.01) than control group,while the DRS total scale and its two factors (attention,concept formation) of MA group were significantly lower than that of MwoA group (P＜ 0.01).During the intermission period,the concept formation and memory scale in MA group was significantly lower than control group(P＜0.05),only memory factor in MwoA group was significantly lower than control group(P＜0.05),while the initiation/perseveration factor scale of MA group was significantly lower than MwoA group(P＜0.05).(3) There Was a negative correlation between OD-ARWMC scale and the total DRS scale as well as its three factors (attention,concept formation,memory)during attack period in MA group(r=-0.584,P＜0.01;r=-0.465,P＜0.05;r=-0.558,P＜0.01;r=-0.439,P＜0.05).There was a negative correlation between OD-ARWMC scale and the total DRS scale as well as concept formation factor during attack period in MwoA group (r=-0.328,P＜ 0.05;r =-0.276,P＜ 0.05).Conclusion Migraine patients may have white matter lesions and cognitive impairment,especially in MA patients and during attack period.