OBJECTIVE To investigate the protective effects and potential mechanism of alisol B 23-acetate on acute alcoholic liver injury in mice. METHODS Fifty male Kunming mice were divided into the blank group， model group， and alisol B 23-acetate low-， medium- and high-dose groups （10， 20， 40 mg/kg）， with 10 mice in each group. Each group was given relevant drug solution or normal saline intragastrically， once a day， for 2 consecutive weeks. On the 15th day， mice in the blank group were given normal saline intragastrically， while the other four groups were given 12 mL/kg white wine intragastrically， twice at six-hour intervals， to establish an acute alcoholic liver injury model. On the 16th day of the experiment， the liver indexes of mice in each group were calculated； the serum levels of alanine transaminase （ALT）， aspartate transaminase （AST）， total cholesterol （TC）， triglycerides （TG）， malondialdehyde （MDA） and glutathione （GSH） were also determined. The histopathological morphology of their liver tissues was observed and scored. The protein expressions of cytochrome P450 2E1 （CYP2E1）， Kelch-like ECH-associated protein 1 （Keap1）， nuclear factor erythroid 2-related factor 2 （Nrf2） and NAD（P）H： quinone oxidoreductase 1 （NQO1） were measured in liver tissue. RESULTS Compared with model group， mice in each dosage group of alisol B 23-acetate showed varying degrees of recovery in body weight， along with improvements in pathological changes in liver tissues such as inflammatory cell infiltration and fatty vacu oles. Their liver indexes， histopathological scores of liver tissue， serum levels of ALT， AST， TC， TG and MDA， as well as the protein expressions of CYP2E1 and Keap1 in liver tissue， were all significantly decreased （ P ＜0.05 or P ＜0.01）. The serum GSH levels and the protein expressions of Nrf2 （except for the alisol B 23-acetate low-dose group） and NQO1 in liver tissue were significantly increased （ P ＜0.05 or P ＜0.01）， and the changes in the above quantitative indicators showed a dose-dependent pattern. CONCLUSIONS Alisol B 23-acetate can ameliorate acute alcoholic liver injury in mice， and its mechanism may be related to improving antioxidant capacity by regulating the Keap1/Nrf2/NQO1 signaling pathway while simultaneously improving liver lipid metabolism-related indexes.

OBJECTIVES: Hysterectomy remains the only definitively effective treatment for diffuse uterine leiomyomatosis (DUL). However, no standardized management strategy exists for DUL patients wishing to preserve fertility. This study summarizes and analyzes 5 cases of individualized treatment in DUL patients desiring fertility preservation, aiming to provide a clinical reference for personalized management of similar patients. METHODS: We retrospectively analyzed the clinical data of 5 DUL patients with fertility intentions admitted to the Department of Obstetrics and Gynecology at Third Xiangya Hospital of Central South University. To preserve fertility, individualized treatment plans were selected based on clinical manifestations and fibroid distribution. One patient received high-intensity focused ultrasound (HIFU); one underwent hysteroscopic myomectomy (HM) combined with laparoscopic myomectomy (LRM); one underwent HIFU combined with HM and LRM; one received drug therapy combined with staged HM; and one underwent HIFU combined with staged HM and drug therapy. Treatment outcomes and pregnancy results were analyzed. RESULTS: After treatment, all 5 patients showed marked improvement in menstrual volume or dysmenorrhea symptoms and significant reduction in uterine volume; mild intrauterine adhesions occurred in 3 cases. All 5 patients achieved successful pregnancy. One patient with chronic hypertension developed severe preeclampsia at 34 weeks and underwent cesarean section, while the remaining 4 delivered at term by cesarean section. Three cases of placenta accreta and 2 cases of postpartum hemorrhage occurred. During long-term follow-up, one patient underwent hysterectomy 2 years postpartum due to increased menstrual volume, while the other 4 remained stable. CONCLUSIONS Individualized treatment tailored to DUL patients' conditions can preserve fertility, support successful pregnancy, and achieve favorable pregnancy outcomes.
Humans ; Female ; Pregnancy ; Leiomyomatosis/therapy* ; Uterine Neoplasms/therapy* ; Adult ; Retrospective Studies ; Fertility Preservation/methods* ; Hysterectomy ; Uterine Myomectomy/methods* ; High-Intensity Focused Ultrasound Ablation ; Pregnancy Outcome

BACKGROUND:Inflammation and oxidative stress contribute to the barriers of regeneration in chronic wound.Oxymatrine has various biological activities,such as anti-oxidation,anti-inflammation and so on,which may have the potential effect of promoting wound healing. OBJECTIVE:To investigate the effect of oxymatrine on wound healing and the protective effect on H2O2-induced oxidative stress injury in human keratinoid cell line HaCaT cells. METHODS:(1)In vivo experiment:Hyaluronic acid methacryloyl hydrogels containing 0,0.05,0.1,0.2 g/L oxymatrine were prepared.A full-layer skin defect model with a diameter of 12 mm was made in the back of 75 diabetic mice and randomly divided into five groups for intervention,with 15 mice in each group.The wounds of the model group were bandaged and fixed.The wounds of the hydrogel group were covered with hyaluronic acid methacryloyl hydrogel.The wounds of the low-dose,moderate-dose and high-dose oxymatrine groups were covered with hyaluronic acid methacryloyl hydrogel containing 0.05,0.1,and 0.2 g/L oxymatrine,respectively,and then bandaged and fixed after light curing.Relevant indicators were detected within 14 days.(2)In vitro experiment:Human keratinocyte line HaCaT was divided into five groups.The normal group was cultured conventionally.H2O2 group and low-,moderate-and high-concentration oxymatrine groups were treated with H2O2 for 4 hours,and then the medium was replaced with medium containing 0,0.05,0.1,and 0.2 g/L oxymatrine,respectively,and the relevant indexes were detected after 24 hours of culture. RESULTS AND CONCLUSION:(1)In vivo experiment:Compared with the model group,the wound healing rate of mice in the hydrogel group had no significant change.The wound healing rate of mice in the low-,moderate-and high-dose oxymatrine group was increased at 7 and 14 days after treatment(P<0.05).Pathological observation of wound section 14 days after treatment showed that compared with the model group,the thickness of regenerated epidermal layer,the number of microvessels,and collagen deposition in the moderate-and high-dose oxymatrine groups were increased(P<0.05).Western blot assay analysis of wound samples 7 days after surgery showed that compared with the model group,the protein expressions of tumor necrosis factor α and interleukin 6 in the moderate-and high-dose oxymatrine groups were decreased(P<0.05).(2)In vitro experiment:CCK8 assay,EdU and Ki67 staining showed that compared with the H2O2 group,the cell proliferation ability of the moderate-and high-concentration oxymatrine groups was significantly increased(P<0.05).Compared with the H2O2 group,mitochondrial membrane potential was increased(P<0.05)and reactive oxygen species content was decreased(P<0.05)in the moderate-and high-concentration oxymatrine groups.Western blot assay results showed that compared with the H2O2 group,the expression levels of Nrf2 nuclear protein,Nrf2 total protein,HO-1 protein,and superoxide dismutase 1 protein were increased in the high-concentration oxymatrine group(P<0.05).(3)These findings confirm that oxymatrine can alleviate oxidative stress damage in HaCat cells and accelerate wound healing by upregulating the levels of Nrf2 and HO-1 protein.

Objective:To evaluate endoscopic nasobiliary drainage (ENBD) combined with nasojejunal tube feeding for elderly patients with severe acute cholangitis.Methods:Data of 43 elderly patients with severe acute cholangitis, who received ENBD combined with nasojejunal tube feeding from January 1, 2016 to May 31, 2018 at Affiliated Hangzhou First People′s Hospital, Zhejiang University School of Medicine were retrospectively analyzed and were included in the observation group, and 43 other patients who received ENBD combined with conventional therapy in the same period were included in the control group with the matching principle of 1∶1. Liver function indices (ALT and AST), nutritional status (Hb, TP and ALB) and inflammation indices (WBC, NEU% and CRP) of the two groups before the operation, 3 days and 7 days of nutritional support after the operation were compared. Adverse reactions (abdominal distention and diarrhea), mortality, hospitalization time and expenses of the two groups were also compared.Results:There were no significant differences in gender composition, mean age, preoperative APACHE-Ⅱ score, NRS2002 score, liver function index, nutritional index, or inflammatory index between the observation group and the control group ( P>0.05). The baseline data of the two groups were comparable. After 3 days of nutritional support, ALT, AST, TP were 21.0 (15.0, 35.5) U/L, 26.0 (21.0, 36.5) U/L, and 64.2±5.2 g/L, respectively in the observation group, and 47.0 (29.5, 82.5) U/L ( P<0.05), 47.0 (29.0, 75.0) U/L ( P<0.05), and 60.5±6.4 g/L ( P<0.05), respectively in the control group. The levels of other indicators were not statistically different at this time point ( P>0.05). At 7 days postoperative nutritional support, ALT, AST, TP, ALB and CRP of the observation group were 22.0 (14.0, 31.5) U/L, 26.0 (20.5, 38.5) U/L, 67.6±5.4 g/L, 34.6±3.7 g/L, and 28.0 (18.5, 35.5) mg/L, respectively, and 43.0 (18.0, 59.5) U/L ( P<0.01), 34.0 (24.0, 60.5) U/L ( P=0.02), 64.5±5.7 g/L ( P=0.01), 31.5±7.0 g/L ( P=0.02), and 34.0 (24.0, 66.5) mg/L ( P<0.05) in the control group. There were no significant differences in the levels of other indicators between the two groups at this time point ( P>0.05). In the observation group, the incidence of diarrhea, abdominal distension, mortality, hospitalization time and hospitalization expenses were 32.6% (14/43), 30.2% (13/43), 9.3% (4/43), 16.0±7.0 days and 40±10 thousand yuan, respectively, and in the control group, the above indicators were 4.7% (2/43) ( P<0.05), 7.0% (3/43) ( P<0.05), 11.6% (5/43) ( P=0.72), 19.3±3.7 days ( P<0.05)) and 53±23 thousand yuan ( P<0.05), respectively. Conclusion:For elderly patients with severe acute cholangitis, enteral nutrition with ENBD can effectively improve the nutritional status, reduce inflammatory reaction, the impact on liver function, and hospital costs, and shorten the hospitalization time, which is suitable for further clinical application.

With the development of stem cell transplantation technology, anti-aging treatment or treatment of degenerative diseases through the input of stem cells has become a research hotspot. Human umbilical cord mesenchymal stem cells (HUCMSCs) are unique precursor cells which are derived from Wharton’s jelly and the perivascular tissue of umbilical cord. They have been identified to be self-renewal and multi-differentiation potential. Currently, a large number of scientific studies have shown that HUCMSCs can achieve anti-aging effects by regenerating and repairing senescent cells, tissues and organs. This article reviews the research advances in biological characteristics, tissue regeneration and repair mechanisms, and anti-aging treatment mechanisms of HUCMSCs in detail. Besides, the current status of preclinical research on HUCMSCs is summarized, suggesting that HUCMSCs is a type of stem cell therapy with good potential and value.

Melanoma is a highly invasive and lethal skin malignant tumor derived from melanocytes. It has the characteristics of high early metastasis and high mortality. In recent years, with the in-depth study of the pathogenesis of melanoma, it has been found that epigenetic modification, especially DNA methylation, is considered to be a universal intrinsic feature of melanoma development and evolution. This article reviews the research progress of abnormal DNA methylation genes in melanoma in detail, and summarizes the biomarker effect of DNA methylation genes, suggesting that the detection of abnormal DNA methylation genes in melanoma patients is hopeful as an early screening index and diagnostic marker for melanoma patients.

With the development of stem cell transplantation technology, anti-aging treatment or treatment of degenerative diseases through the input of stem cells has become a research hotspot. Human umbilical cord mesenchymal stem cells (HUCMSCs) are unique precursor cells which are derived from Wharton’s jelly and the perivascular tissue of umbilical cord. They have been identified to be self-renewal and multi-differentiation potential. Currently, a large number of scientific studies have shown that HUCMSCs can achieve anti-aging effects by regenerating and repairing senescent cells, tissues and organs. This article reviews the research advances in biological characteristics, tissue regeneration and repair mechanisms, and anti-aging treatment mechanisms of HUCMSCs in detail. Besides, the current status of preclinical research on HUCMSCs is summarized, suggesting that HUCMSCs is a type of stem cell therapy with good potential and value.

Melanoma is a highly invasive and lethal skin malignant tumor derived from melanocytes. It has the characteristics of high early metastasis and high mortality. In recent years, with the in-depth study of the pathogenesis of melanoma, it has been found that epigenetic modification, especially DNA methylation, is considered to be a universal intrinsic feature of melanoma development and evolution. This article reviews the research progress of abnormal DNA methylation genes in melanoma in detail, and summarizes the biomarker effect of DNA methylation genes, suggesting that the detection of abnormal DNA methylation genes in melanoma patients is hopeful as an early screening index and diagnostic marker for melanoma patients.

Polycyclic aromatic hydrocarbons (PAHs) are widely found in the environment, and comparing to adults, children are more vulnerable to PAHs exposure. Urinary metabolites of PAHs are used as preferred biomarkers to estimate the PAHs exposure. Systematic review on the internal exposure level of children and adolescents is rare. We aimed to calculate the internal exposure levels of PAHs in children and adolescents and compare the levels of PAHs internal exposure in various children groups. We searched PubMed, OVID, Web of Science, EBSCO, ACS, and four Chinese databases, and all studies examining the urinary concentrations of PAHs in children and adolescent were identified. The total exposure level of 11 PAHs metabolites were pooled. Standard mean difference (SMD) and 95% confidence intervals (CIs) of PAHs urinary concentration were calculated and pooled by RevMan5.3 to compare the exposure levels of different children groups. We found that 1-OHPyr, 2-OHNap, 2-OHFlu, 3-OHPhe, and 4-OHPhe were five PAHs metabolites most commonly studied in existing studies in children, and their total exposure levels were 0.38 ± 0.98, 2.32 ± 4.83, 0.81 ± 1.54, 0.09 ± 0.14, 0.03 ± 0.10 μmol/mol creatinine, respectively. The meta-analysis showed that the levels of 1-OHPyr were higher in higher environmental exposure group (SMD = 0.21, 95% CI = 0.03~0.40), ETS exposure group (SMD = 0.31, 95% CI = 0.08~0.54), and 6~11 years group (SMD = 0.16, 95% CI = 0.09~0.24); the level of 2-OHNap (SMD = 0.27, 95% CI = 0.01~0.53) was higher in higher environmental exposure group; however, the levels of 3-OHPhe (SMD = - 0.34, 95% CI = - 0.57~- 0.12) and 4-OHPhe (SMD = - 0.48, 95% CI = - 0.69~- 0.28) were higher in lower environmental exposure group. The levels of 1-OHPyr (SMD = - 0.01, 95% CI = - 0.11~0.10) and 2-OHNap (SMD = 0.01, 95% CI = - 0.20~0.22) were not statistically different between boys and girls. In conclusions, we found that the internal diversity of PAHs existed in children and adolescents, and the level of 1-OHPyr in children and adolescents was in higher status compared with non-occupational people who do not smoke.

Objective: To study the effect of miR-194-3p on the migration of keloid fibroblasts. Methods: Differentially expressed miRNA were screened by gene chip in 8 human keloid and normal tissues. The down regulated miR-194-3p was selected for study and its binding to RUNX2 was predicted by MiRDB, and verified by fluorescent reporter gene in human keloid fibroblasts (HKFs) and passage 3 keloid cells, respectively. The effect of miR-194-3p on the migration of fibroblasts was detected by transwell assay. Western blot and real-time PCR were used to analyze the effect of miR-194-3p on RUNX2 and MMP2 expression in HKFs. The results were analyzed by SPSS 19.0 software and compared by non-paired t test. P<0.05 was considered statistically significant. Results: There were abnormal expressions of miR-721, miR-21-3p, miR-382-3p, miR-194-3p, miR-3107-5p and miR-144-5p in keloid. miRDB software analysis showed that miR-194-3p and RUNX2 had targeted binding sites. Reporter gene experiments showed that miR-194-3p inhibited the activity of RUNX2 by about 50% compared with the control group (t=2.7764, P=0.0005). MiR-194-3p could significantly inhibit the expression of RUNX2 and MMP2, and inhibited the migration of keloid fibroblasts (t=2.7764, P<0.05). Conclusion MiR-194-3p may inhibit the migration of fibroblasts by inhibiting the activity of RUNX2 in keloid.