Objective To investigate the effect of folic acid on the DNA methylation of tumorrelated genes promoters in healthy human peripheral blood mononuclear cells(PBMC). Methods Ten healthy volunteers were divided into two groups, and were randomized to receive either 5 mg folic acid (n=5)or placebo(n = 5) , one time per day for 3 months. The serum folic acid concentration was detected with chemiluminescence enzyme immunoassay kit before and after the intervention. The methylation statuses of five tumor-related genes promoter, including oncogenes c-myc, c-Ha-ras,tumor suppressor genes p16INK4A, E-cadherin and mismatch repair gene hMLH1 in PBMC were detected by bisufite sequencing. Results After folic acid intervention, the level of serum folic acid increased significantly in intervention group (t= -4. 739,P<0. 05) , however no significant difference in control group. After three-month folic acid intervention, the level of methylation of oncogene c-myc promoter increased from 4%, 3. 3%, 4. 1% before intervention, one week after intervention, one month after intervention respectively to 8%(t= -4. 079,P<0. 05), while no significant change in placebo taken group. Before and after the folic acid intervention, there was no significant difference of DNA methylation of other tumor-related genes promoter, including c-Ha-ras、E-cadherin、p16INK4Aand hMLH1. Conclusion Folic acid intervention can up-regulate DNA methylation of oncogene c-myc promoter, but can not affect the promoter methylation status of tumor suppressor genes E-cadherin,p16INK4Aand hMLH1.

Objectives:To assess bowel function and quality of life in patients with ulcerative colitis (UC)after ileal pouch anal anastomosis (IPAA).Methods:Clinical data of 37 UC patients after IPAA between 2014 and 2017 were retrospectively analyzed at Sir Run Run Shaw Hospital School of Medicine Zhejiang University. The IBDQ and Bowel Function questionnaire were used for analyzing correlation between clinical variables and quality of life or bowel function.Results:Laparoscopic operation was performed in 12 cases at stage 2 and 25 cases at stage 3. Postoperative defecation of stage 3 patients were better than that of stage 2 ( t=6.72, P<0.05). The number of daily defecation in age >45-year-old group was more than that in <45-year-old ( t=3.49, P<0.05), and the rate of evening stool seepage in the older group was higher than in the younger group( t=5.28, P<0.05). The total score of intestinal symptoms of IBDQ in patients of pouchitis was lower than that without pouchitis ( r=0.330, P<0.05). The total score in age >45 in terms of systemic symptoms ( r=0.349, P<0.05) and emotional function ( r=0.379, P<0.05) was higher than age <45. Conclusions:Outcomes of UC patients after IPAA are satisfactory, bowel function and quality of life is related with age, and stage of IPAA affect postoperative defecation.

Objective To compare a novel mirror-overlap method with the traditional manual measurement and the subjective assessment in assessing breast symmetry after oncoplastic surgery.Methods 59 patients with breast cancer who underwent conservation/reconstruction surgery were recruited.The post-operative assessment for breast symmetry was conducted using manual measurement,subjective assessment by the patient,their family member and a nurse,and the mirror-overlap method respectively.The latter method involved using the Photoshop to assess the area differences in breast outlines and shadows created by a flashlight when bilateral images were overlapped in the axis of midline.Results The distance differences between bilateral breasts measured using manual method were negatively correlated with symmetric coefficients in the mirror-overlap method (P＜0.05).There was a positive correlation between the average scores in the subjective assessment and symmetric coefficients of mirror-overlap method (P＜0.05).Conclusion The mirror-overlap method is an easy,feasible and cheap method which collects 3D breast information and provides an effective approach to assess breast symmetry after oncoplastic surgery.

BACKGROUND:Some studies have found that local application of alendronate can promote osteogenesis,but less is reported on the process of distraction osteogenesis. OBJECTIVE:To observe the promoting effect of alendronate on rapid mandibular distraction in a rabbit model and explore its possible mechanism. METHODS:Thirty-six male New Zealand white rabbits were randomly divided into groups A,B and C(n=12 per group)after operation and rapid distraction(3-day delay period followed by 3-day distraction at 1.5 mm/12 hours).At the 1st,3rd and 7th days of the consolidation period,animal were injected with 200 μg/kg alendronate in group A and 100 μg/kg alendronate in group B,while those in group C were treated as controls.CT scanning and dual energy X-ray bone mineral density measurement were performed at 4 and 8 weeks of the consolidation period.After the radionuclide scanning was completed at the 4th week,several animals were sacrificed and the samples were collected for western blot assay and tartrate resistant acid phosphatase staining.A three-point bending test was performed after the animals were sacrificed at the 8th week. RESULTS AND CONCLUSION:CT results showed that bone formation in the distraction space of group B was significantly better than that in groups A and C.At the 4th week,the bone mineral density in group B was(0.092±0.010)g/cm2,which was 1.26 times higher than that in group A(P＜0.001)and 1.28 times higher than that in group C(P＜0.001).At the 8th week,the bone mineral density in group B was(0.175±0.029)g/cm2,which was 1.38 times higher than that in group A(P＜0.001)and 1.45 times higher than that in group C(P＜0.001).Tartrate resistant acid phosphatase staining showed that the number of osteoclast-like cells in group C were 2.83 times more than that in group A(P＜0.001)and 2.21 times more than that in group B(P＜0.001).The radionuclide intensity was higher in group C than in groups A and B.Western blot assay results showed that the expression of Runx2 was significantly stronger in group B than in groups A and C.The maximum biomechanical load in group B was(158.48±23.21)N,which was 1.26 times higher than that in group A(P=0.007)and 1.31 times higher than that in group C(P=0.003).To conclude,the low concentration of alendronate may promote rapid distraction osteogenesis of the rabbit mandible by inhibiting osteoclast signals.

Objective To investigate the clinical efficacy of low-dose plasma exchange (PE) combined with artificial liver in the treatment of acute-on-chronic liver failure (ACLF) and its effect on mortality rate after stratification. Methods A total of 272 ACLF patients who were admitted to Department of Infection and Hepatology, The First Affiliated Hospital of Kunming Medical University, from January 2018 to December 2020 were enrolled and divided into low-dose PE+double plasma molecular absorption system (DPMAS)/hemoperfusion (HP) group ( n =190) and medical treatment group( n =82). Laboratory markers were collected before and after treatment, and clinical outcome was compared between the two groups; stratified analysis (early stage, early-middle stage, late stage or types A, B, C) was performed for the two groups according to Diagnostic and treatment guidelines for liver failure (2018 edition), and all patients were followed up to observe general status and death at 12 weeks (short-term) and 48 weeks (long-term) after discharge. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the paired samples t -test was used for comparison before and after treatment; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Wilcoxon test was used for comparison before and after treatment; the chi-square test was used for comparison of categorical data between groups. Results Both low-dose PE combined with DPMAS/HP and medical treatment alone could reduce the levels of alanine aminotransferase (ALT), aspartate aminotransferase, total bilirubin (TBil), and blood ammonia and increase the level of albumin (Alb), and both groups had significant changes in these indices after treatment (all P < 0.05). Compared with medical treatment alone, low-dose PE combined with DPMAS/HP better reduced ALT, TBil, and blood ammonia and improved Alb, with significant changes in these indices after treatment (all P < 0.05). Low-dose PE combined with DPMAS/HP could significantly reduce bile acid, international normalized ratio, neutrophil-lymphocyte ratio, and MELD score and increase platelet-to-white blood cell ratio (all P < 0.05), while medical treatment alone could not improve the above indices (all P > 0.05). Compared with medical treatment alone, low-dose PE combined with DPMAS/HP could reduce the short-term mortality rate of ACLF patients, especially the short-term mortality rate of ACLF patients with early-stage, early-middle-stage or type A ACLF, and there were significant differences between the two groups (all P < 0.05). In the low-dose PE+DPMAS/HP group, the patients with early-stage ACLF had significantly lower short- and long-term mortality rates than those with late-stage ACLF, and the patients with type A ACLF had significantly lower short- and long-term mortality rates than those with type C ACLF (all P < 0.05). Conclusion Low-dose PE combined with DPMAS/HP has good clinical efficacy and can effectively reduce the short-term mortality rate of ACLF, especially the short-term mortality rate of patients with early-stage, early-middle-stage, or type A ACLF.

ObjectiveTo investigate the clinical features and risk factors of primary biliary cholangitis （PBC） comorbid with metabolic associated fatty liver disease （MAFLD） and the interaction between the two diseases. MethodsA total of 187 patients who were diagnosed with PBC， MAFLD， or PBC with MAFLD in The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2022 were enrolled and divided into PBC group with 70 patients， PBC+MAFLD group with 38 patients， and MAFLD group with 79 patients. Related data were collected， including general information， clinical symptoms， serological parameters， transient elastography （FibroScan）， and non-invasive fibrosis markers， which were compared between the three groups. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups， the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the binary Logistic regression analysis was used for multivariate analysis. ResultsThere were significant differences between the three groups in sex， age， height， weight， body mass index （BMI）， and history of autoimmune diseases （P<0.05）. In the PBC+MAFLD group， female patients accounted for 89.5%， with a mean age of 57.26±12.72 years and a BMI of 23.35±3.70 kg/m²， and in the PBC group， the detection rate of autoimmune diseases was 25.7% （18 patients）. There were significant differences between the three groups in the incidence rates of weakness， poor appetite， pruritus， jaundice， varices， ascites， and splenomegaly （all P<0.05）. The PBC+MAFLD group had the common symptoms of weakness in 18 patients （47.4%）， poor appetite in 15 patients （39.5%）， abdominal pain in 14 patients （36.8%）， and abdominal distension in 16 patients （42.1%）； the MAFLD group had the common symptoms of abdominal pain in 34 patients （43%） and abdominal distension in 32 patients （40.5%）； the PBC group had the common symptoms of weakness in 37 patients （52.9%）， poor appetite in 25 patients （35.7%）， jaundice in 25 patients （35.7%）， abdominal pain in 18 patients （25.7%）， abdominal distension in 25 patients （35.7%）， varices in 19 patients （27.9%）， ascites in 23 patients （32.9%）， and splenomegaly in 44 patients （62.9%）. The PBC+MAFLD group had a controlled attenuation parameter （CAP）， which was higher than that of the PBC group， and the PBC group had significantly higher levels of liver stiffness measurement， aspartate aminotransferase-to-platelet ratio index （APRI）， and fibrosis-4 （FIB-4） than the MAFLD group （all P<0.05）. The factors without multicollinearity were included in the regression analysis， and with the PBC group as the reference group， FIB-4 （odds ratio ［OR］=0.218， 95% confidence interval ［CI］： 0.069 ‍—‍ 0.633， P<0.05） and history of autoimmune diseases （OR=0.229， 95%CI： 0.067‍ — ‍0.810， P<0.05） were influencing factors for the onset of PBC with MAFLD； with the MAFLD group as the reference group， ALT （OR=0.157， 95%CI： 0.025‍ —‍ ‍1.000， P<0.05） and TBil （OR=0.995， 95%CI： 0.990‍‍ — ‍0.999， P<0.05） were influencing factors for the onset of PBC with MAFLD. ConclusionPBC with MAFLD lacks specific clinical manifestations， and PBC patients tend to have more severe clinical manifestations and a higher incidence rate of liver function decompensation. PBC comorbid with MAFLD may not aggravate the disease progression of PBC.

cFos is one of the most widely-studied genes in the field of neuroscience. Currently, there is no systematic database focusing on cFos in neuroscience. We developed a curated database-cFos-ANAB-a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice, comprising 398 brain nuclei and sub-nuclei, and five associated behaviors: pain, fear, feeding, aggression, and sexual behavior. Direct relationships among behaviors and nuclei (even cell types) under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications. Moreover, overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized, leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown circuits. Using the analysis function of cFos-ANAB, multi-layered pictures of networks and their relationships can quickly be explored depending on users' purposes. These features provide a useful tool and good reference for early exploration in neuroscience. The cFos-ANAB database is available at www.cfos-db.net .
Animals ; Fear ; Mice ; Neurons ; Proto-Oncogene Proteins c-fos ; Rats

cFos is one of the most widely-studied genes in the field of neuroscience. Currently, there is no systematic database focusing on cFos in neuroscience. We developed a curated database—cFos-ANAB—a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice, comprising 398 brain nuclei and sub-nuclei, and five associated behaviors: pain, fear, feeding, aggression, and sexual behavior. Direct relationships among behaviors and nuclei (even cell types) under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications. Moreover, overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized, leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown circuits. Using the analysis function of cFos-ANAB, multi-layered pictures of networks and their relationships can quickly be explored depending on users’ purposes. These features provide a useful tool and good reference for early exploration in neuroscience. The cFos-ANAB database is available at www.cfos-db.net.