Objective:To explore the therapeutic effect of compound Kuijie Ankang Decoction on ulcerative colitis (UC) model mice by non targeted metabonomics; To explore its mechanism.Compound Kuijie Ankang.Methods:The mice were randomly divided into blank control group, model group, Kuijie Ankang Decoction group and sulfasalazine group, with 12 mice in each group. Except the blank control group, the other groups were given 1.5% DSS solution for free drinking to prepare UC model. After successful modeling, Kuijie Ankang Decoction group was intragastrically administered with compound Kuijie Ankang Decoction of 9.68 g/kg, sulfasalazine group was intragastrically administered with sulfasalazine capsule suspension of 320 mg/kg, model group and blank control group were intragastrically administered with equal volume of purified water, once a day, for 7 consecutive days. The body mass and disease activity index (DAI) score of mice were measured. ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the colon tissue of mice; the protein expressions of Claudin-1 and Zo-1 in colon tissue were detected by immunofluorescence method. HE staining was used to observe the pathological changes in the colon, and UHPLC-OE-MS technology was used to analyze the endogenous metabolite structure of mouse colon tissue, differential metabolites and related metabolic pathways were screened.Results:Compared with the model group, the colon length in Kuijie Ankang Decoction group and sulfasalazine group increased ( P<0.01), the DAI score decreased ( P<0.01), the levels of TNF-α, IL-1β and IL-6 in colon tissue decreased ( P<0.01), the level of IL-10 increased ( P<0.01), and the average optical density of Claudin-1 and Zo-1 protein increased ( P<0.01 or P<0.05). Metabolomics analysis identified 26 potential differential metabolites, including nicotinamide adenine dinucleotide, guanine, gamma aminobutyric acid, and thiamine, affecting 26 key metabolic pathways, including lysine biosynthesis, thiamine metabolism, cysteine and methionine metabolism. Conclusion:Kuaijie Ankang Decoction may improve metabolites such as Gamma aminobutyric acid and thiamine through metabolic pathways such as lysine biosynthesis to alleviate inflammatory reactions, thereby exerting therapeutic effects on ulcerative colitis in mice.

OBJECTIVE To investigate the effects of erianin （ERI） on the apoptosis of ovarian granulosa cells in rats with polycystic ovary syndrome （PCOS） and its mechanism. METHODS PCOS rat model was constructed by subcutaneous injection of dehydroepiandrosterone， and the successfully constructed rats were randomly divided into PCOS group， ERI low-dose， medium- dose and high-dose groups （10， 20， 40 mg/kg） and ERI high dose + verteporfin group （40 mg/kg ERI + 10 mg/kg verteporfin）， with 10 rats in each group. Another 10 normal rats were selected as the normal group. Rats in each administration group were given corresponding dose of ERI and/or intraperitoneal injection of vitiporfin， and rats in the PCOS group and normal group were orally administered an equal volume of 1% dimethyl sulfoxide， once a day， for 6 consecutive weeks. After administration， the body weight， fasting blood glucose （FPG）， serum levels of estradiol （E2）， testosterone （T）， follicle stimulating hormone （FSH） and luteinizing hormone （LH） were detected in each group； morphological changes in ovarian tissue were observed， and the apoptosis of ovarian tissue cells was analyzed. Apoptosis-associated proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase-3] and Hippo-YAP signaling pathway associated proteins [large tumor suppressor kinase 1 （LATS1）， phosphorylated LATS1 （p-LATS1） and Yes associated protein （YAP）， phosphorylated YAP （p-YAP）， transcriptional co-activator with PDZ binding motif （TAZ）] were detected in ovarian tissue. RESULTS Compared with PCOS group， the ovarian polycystic characteristics of the ERI low-dose， medium-dose，and high-dose groups were reduced， the number of atretic follicles was reduced， and the granulosa cell layer was thickened； the body mass， FPG， T， LH， LH/FSH， the number of cystic follicles， cell apoptosis index， protein expressions of Bax， Caspase-3， p-LATS1 and p-YAP were greatly decreased （P＜0.05）； the number of corpus luteum， protein expressions of E2， Bcl-2， LATS1， YAP and TAZ were greatly increased （P＜0.05）. Compared with ERI high-dose group， the above indexes in ERI high-dose + vitiporfin group were inhibited （P＜0.05）. CONCLUSIONS ERI can promote the proliferation of ovarian granulosa cells and improve the level of sex hormones in PCOS rats， and its mechanism of action may be related to the inhibition of the Hippo-YAP signaling pathway.

OBJECTIVE To investigate the effects of erianin （ERI） on the apoptosis of ovarian granulosa cells in rats with polycystic ovary syndrome （PCOS） and its mechanism. METHODS PCOS rat model was constructed by subcutaneous injection of dehydroepiandrosterone， and the successfully constructed rats were randomly divided into PCOS group， ERI low-dose， medium- dose and high-dose groups （10， 20， 40 mg/kg） and ERI high dose + verteporfin group （40 mg/kg ERI + 10 mg/kg verteporfin）， with 10 rats in each group. Another 10 normal rats were selected as the normal group. Rats in each administration group were given corresponding dose of ERI and/or intraperitoneal injection of vitiporfin， and rats in the PCOS group and normal group were orally administered an equal volume of 1% dimethyl sulfoxide， once a day， for 6 consecutive weeks. After administration， the body weight， fasting blood glucose （FPG）， serum levels of estradiol （E2）， testosterone （T）， follicle stimulating hormone （FSH） and luteinizing hormone （LH） were detected in each group； morphological changes in ovarian tissue were observed， and the apoptosis of ovarian tissue cells was analyzed. Apoptosis-associated proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase-3] and Hippo-YAP signaling pathway associated proteins [large tumor suppressor kinase 1 （LATS1）， phosphorylated LATS1 （p-LATS1） and Yes associated protein （YAP）， phosphorylated YAP （p-YAP）， transcriptional co-activator with PDZ binding motif （TAZ）] were detected in ovarian tissue. RESULTS Compared with PCOS group， the ovarian polycystic characteristics of the ERI low-dose， medium-dose，and high-dose groups were reduced， the number of atretic follicles was reduced， and the granulosa cell layer was thickened； the body mass， FPG， T， LH， LH/FSH， the number of cystic follicles， cell apoptosis index， protein expressions of Bax， Caspase-3， p-LATS1 and p-YAP were greatly decreased （P＜0.05）； the number of corpus luteum， protein expressions of E2， Bcl-2， LATS1， YAP and TAZ were greatly increased （P＜0.05）. Compared with ERI high-dose group， the above indexes in ERI high-dose + vitiporfin group were inhibited （P＜0.05）. CONCLUSIONS ERI can promote the proliferation of ovarian granulosa cells and improve the level of sex hormones in PCOS rats， and its mechanism of action may be related to the inhibition of the Hippo-YAP signaling pathway.

Objective:To study the risk factors for sepsis with acute pancreatitis (AP) in the intensive care unit, Nomogram models were constructed and evaluatedand.Methods:Clinical data of 306 AP patients were admitted to the First Department of Critical Care Medicine. The Second Affiliated Hospital of Anhui Medical University from October 2013 to October 2023 were included, they were divided into sepsis group and non-sepsis group according to whether sepsis occurred. Baseline data and laboratory test results of the two groups were compared. The study subjects were randomly(random number) divided into training set and verification set, and the optimal variables were selected by LASSO regression. Then multivariate Logistic regression analysis was performed to construct a Nomogram risk prediction model. Then the prediction efficiency of the model was evaluated.Results:A total of 306 AP patients were included, including 127 patients with sepsis and 179 patients without sepsis. According to the ratio of 7:3, 215 cases were randomly (random number) divided into the training set and 91 cases were verified. Multivariate Logistic regression analysis showed that BMI, APACHEⅡ score, platelet, IL-6, total bilirubin and complications were independent risk factors for sepsis in patients with AP. According to the above risk factors, a Nomogram prediction model was established. The area under ROC curve of the model in training set and verified set were 0.913 (95% CI 0.875-0.951) and 0.901 (95% CI 0.837-0.965) respectively. The calibration curve shows that the predicted probability is basically consistent with the actual probability. Decision curve analysis shows that it has good clinical net benefit in a large threshold range. Conclusions:The independent risk factors of AP associated with sepsis in ICU are BMI, APACHEⅡscore, platelet, IL-6, total bilirubin and complications. The Nomogram risk predictive model based on these factors has good predictive power.

Human epidermal growth factor (hEGF) can be applied in the treatment of surgical trauma (burns, scalds), tissue repair, skin moisturizing, beauty, skincare, etc. However, the low expression and high cost limit the application of hEGF. In order to improve the expression level of hEGF and reduce the production cost, considering the high expression of polyhedrin, this study fused a partial sequence of polyhedrin with hEGF and expressed the fused sequence by using a silkworm baculovirus expression vector system. In view of the small molecular weight of hEGF, we connected hEGF genes in series and optimized the codons to construct multiple fusion expression vectors by fusing different partial sequences of polyhedrin at the N-terminus. The results showed that through the above strategy, the protein expression level of hEGF was significantly increased. The expression vector containing three concatenated hEGF genes with optimized codons and fused with the sequence encoding 25 or 35 residues at the N-terminus of polyhedrin showed the highest expression level.
Humans ; Epidermal Growth Factor/biosynthesis* ; Genetic Vectors/genetics* ; Recombinant Fusion Proteins/biosynthesis* ; Animals ; Bombyx/metabolism* ; Occlusion Body Matrix Proteins/genetics* ; Nucleopolyhedroviruses/genetics* ; Amino Acid Sequence

Objective:To systematically evaluate the correlation of high sensitivity C-reactive protein (hs-CRP) with contrast-induced nephropathy (CIN) in patients following coronary angiography (CAG) or percutaneous coronary intervention (PCI).Methods:PubMed, web of science, CBM, CNKI and Wanfang Data were searched for studies on hs-CRP levels in patients undergoing CAG or PCI patients from the incipience of the database to March 7, 2021. Meta-analysis was performed by RevMan 5.3 and Stata 12.0 software.Results:Fourteen related studies were included involving 11 885 patients undergoing CAG or PCI (1 034 cases with CIN and 10 851 cases without CIN). The results of meta-analysis showed that the level of hs-CRP in CIN group was significantly higher than that in non-CIN group (WMD=3.77,95 %CI:2.80—4.74, P<0.001, I2=93%), patients with higher levels of hs-CRP before CAG or PCI were more likely to develop CIN. Sensitivity analysis shows that the results of this study had good stability. The results of subgroup analysis show that the differences in sample size, study population, geographical location and the definition of CIN were statistically significant. Conclusion:Available evidence shows that high hs-CRP level is a risk factor for CIN in patients undergoing CAG or PCI, large sample trials are still needed to support this conclusion.

Objective:To analyze the distribution and composition characteristics of jellyfish stings in various coastal baths in Qinhuangdao City from 2017 to 2019, and to provide scientific basis for the prevention, control and early warning of jellyfish stings.Methods:Statistics and analysis of the age, gender, time of stings, location of injury, first symptoms, and playing time in the sea at the time of the sting, etc. of people with jellyfish stings in various bathing beaches along the coast of Qinhuangdao from 2017 to 2019 (July to August) were conducted.Results:The number of jellyfish stings in the coastal bathing beaches of Qinhuangdao City in 2017, 2018, and 2019 was decreasing year by year, with 1 890, 492, and 171 cases respectively. Among them, Qianshuiwan Bathing Beach and Dongshan Bathing Beach had more stings (60.90% and 35.08% respectively in 2017, 24.39% and 64.23% respectively in 2018, 16.96% and 16.42% respectively in 2019). There was no significant change in the gender and age distribution of jellyfish stings each year [57.99% males in 2017, with a median age of 13 (8, 31) years old; 63.21% males in 2018, with a median age of 25 (8, 29) years old; and 59.65% males in 2019, with a median age of 12 (7, 31) years old]. Stings were mainly located at the lower limbs (the proportion of lower limb injuries: 46.54% in 2018, 45.61% in 2019), followed by upper limbs (upper arm, elbow, forearm), trunk, etc. The first symptom was mainly pain (89.43% in 2018, 38.29% in 2019), followed by rash (64.43% in 2018, 59.43% in 2019), numbness, blisters, etc. Sting incidents mainly occurred from 13:00 to 17:59 (the proportion of sting incidents in this time period in 2018 and 2019 were 68.09% and 52.63%, respectively).Conclusions:Jellyfish stings in coastal baths in Qinhuangdao City are mainly distributed in Qianshuiwan Baths and Dongshan Baths. The management of these sea areas should be strengthened, and scientific publicity and medical rescue should be strengthened to prevent jellyfish stings in peak hours and related baths.

Objective:The clinical efficacy, safety and quality of life in female patients with stress urinary incontinence (SUI)treated by midurethral sling were studied by multicenter retrospective study.Methods:From January 2018 to December 2018, 531 female patients with severe stress urinary incontinence from seven domestic urinary center were included in this study, including 78 cases from General Hospital of Central Theater Command, 122 cases from Shanghai Jiao tong University School of Medicine Affiliated Ren Ji Hospital, 67 cases from Shanghai Jiaotong University Affiliated First People’s Hospital, 68 cases from People’s Hospital of Jiangsu Province, 71 cases from The First Affiliated Hospital of Xi’an Jiaotong University, 65 cases from Zhejiang Provincial People’s hospital, 60 cases from Xiamen University First Affiliated Hospital. Among the 531 patients, 214 cases received TVT sling with an average age of (58.14±10.16) years. 181 cases were in postmenopausal(84.6%). The number of births ≥2 times was 89 (41.6%) cases. The score of ICI-Q-SF was 16.00±1.73. There were 166 cases of moderate incontinence (77.6%) and 48 cases of severe incontinence (22.4%). There were 317 patients in the TOT/TVT-O group with an average age of (58.33±10.25) years. 247 cases were in postmenopausal(77.9%). The number of births ≥2 times was 120 (37.8%) cases. The score of ICI-Q-SF was 15.79±1.75. There were 256 cases of moderate incontinence (80.8%) and 61 cases of severe incontinence (19.2%). There was no statistically significant difference in general data parameters between the two groups ( P>0.05). 1, 6, 12 months after the operation, the two groups of patients incontinence questionnaire Summary(ICI-Q-SF), common complications and Patient Global Impression of Improvement(PGI-I), satisfaction evaluation follow-up. ICI-Q-SF score improved > by 50% (cure + significant improvement) and 1-hour pad test <10 g (qualitative index) were used as the evaluation index of surgical success. Result:Both of the two surgical methods have high successive rate. There was no significant difference between 94.9% (203/214) of the TVT group and 93.7% (297/317) of the TOT/ TVT-O group ( P>0.05). Postoperative improvement of urinary incontinence (cure rate) [88.3% (189/214)]in the TVT group was slightly higher than that in the TOT/ TVT-O group [77.0% (244/317)] ( P<0.05). There was no change in the recurrence rate of urinary incontinence in the follow-up 6 and 12 months after the operation. There was no statistically significant difference between 4.4% (9/203) in the TVT group and 5.4% (16/297) in the TOT/TVT-O group ( P>0.05). The subjective cure rate 12 months after the operation was 96.3% (206/214) in the TVT group and 95.9% (304/317) in the TOT/TVT-O group ( P>0.05). 10 patients occurred bladder perforation occurred in the TVT group, and no bladder perforation occurred in the TOT/TVT-O group ( P<0.001). The incidence of pain and discomfort in the TVT group was significantly lower at 1.9% than that in the TOT/TVT-O group at 6.9% ( P<0.01). There was no statistically significant difference between the two groups in the incidence of complications such as dysuria/urinary retention, frequent urination/urgency incontinence. Both of them exposed sling ( P>0.05). Conclusion:Both TVT and TOT/TVT-O sling can effectively treat female stress urinary incontinence, and both can improve the sexual satisfaction of patients after the surgery, with fewer complications and other advantages. The selection of specific surgical methods in clinical practice can be individualized according to the patient's physical conditions, clinical needs and the operation methods familiar to doctors.

Enhancers activate transcription in a distance-, orientation-, and position-independent manner, which makes them difficult to be identified. Self-transcribing active regulatory region sequencing (STARR-seq) measures the enhancer activity of millions of DNA fragments in parallel. Here we used STARR-seq to generate a quantitative global map of rice enhancers. Most enhancers were mapped within genes, especially at the 5' untranslated regions (5'UTR) and in coding sequences. Enhancers were also frequently mapped proximal to silent and lowly-expressed genes in transposable element (TE)-rich regions. Analysis of the epigenetic features of enhancers at their endogenous loci revealed that most enhancers do not co-localize with DNase I hypersensitive sites (DHSs) and lack the enhancer mark of histone modification H3K4me1. Clustering analysis of enhancers according to their epigenetic marks revealed that about 40% of identified enhancers carried one or more epigenetic marks. Repressive H3K27me3 was frequently enriched with positive marks, H3K4me3 and/or H3K27ac, which together label enhancers. Intergenic enhancers were also predicted based on the location of DHS regions relative to genes, which overlap poorly with STARR-seq enhancers. In summary, we quantitatively identified enhancers by functional analysis in the genome of rice, an important model plant. This work provides a valuable resource for further mechanistic studies in different biological contexts.
Acetylation ; Base Sequence ; Deoxyribonuclease I ; metabolism ; Enhancer Elements, Genetic ; Epigenesis, Genetic ; Genes, Plant ; Genomics ; methods ; Histone Code ; genetics ; Histones ; metabolism ; Models, Genetic ; Oryza ; genetics ; Promoter Regions, Genetic ; genetics ; Repetitive Sequences, Nucleic Acid ; genetics ; Sequence Analysis, DNA ; Transcription, Genetic

Objective: To investigate the distribution of polymorphisms of glucagon-like peptide-1 receptor gene (GLP-1R) rs10305420 and rs3765467 in Chinese Han type 2 diabetic patients, and the effects on body weight, blood glucose and serum lipid levels. Methods: Two SNPs of GLP-1R rs3765467 and rs10305420 were genotyped by Sanger dideoxy termination sequencing method. The racial difference and the association between the gene polymorphisms and the metabolic markers including BMI, serum lipids and blood glucose were analyzed. Results: The distribution of gene polymorphisms was consistent with the Hardy-Weinberg equilibrium. High-density lipoprotein (HDL-C) levels were significantly lower in the rs10305420 T allele carriers than in the CC genotype (1.00±0.18 vs 1.09±0.22, P=0.02). The triglyceride (TG) level of the rs3765467 A allele carrier was higher than that of the GG type (2.75±2.19 vs 2.07±1.36, P=0.03). The allele frequency of rs10305420 C/T was highly statistically significant compared with European population (P=0.000 3). The allele frequency of rs3765467 G/A was statistically different from that of European and African populations (P<0.01). Conclusions The two genetic polymorphisms were significantly associated with lipid levels in patients with type 2 diabetes, and there was a significant racial difference in the frequency distribution of the two variants.