Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Objective To investigate the value of interleukin(IL)-6 and kidney injury molecule(Kim)-1 in the early prediction of contrast-induced pnephropathy(CIN)after percutaneous coronary intervention(PCI)in patients with coronary heart disease.Methods A total of 730 patients with coronary heart disease who underwent PCI were retrospectively collected,divided into CIN group(n=46)and non-CIN group(n=684),and the medical records of the two groups were compared,and the relationship between Kim-1 and IL-6 of renal injury and CIN was analyzed by binary regression,and the receiver operating characteristic(ROC)curve was used to explore the predictive value of these two markers on CIN after PCI for coronary heart disease.Results There was no significant difference between two groups in terms of preoperative IL-6(P=0.467)and Kim-1(P=0.643),and 48h and 72h after PCI,IL-6 and Kim-1 in CIN group was higher than that in non-CIN group(P＜0.001),and IL-6 and Kim-1 in CIN group was higher than that in before surgery(P＜0.001).48h postoperative IL-6(OR=1.884,P=0.002),48h postoperative Kim-1(OR=1.409,P＜0.001)and 72h postoperative IL-6(OR=1.377,P＜0.001)and 72 hours postoperative Kim-1(OR=1.092,P=0.004)were independent risk factors for CIN.The ROC curve showed that when used as a diagnostic marker for CIN,the area under the curve(AUC)of IL-6(48h),IL-6(72h)were 0.837,0.782,AUC of 48h Kim-1 and 72h Kim-1 were 0.820 and 0.827,respectively.Conclusion IL-6 and Kim-1 are independent risk factors for CIN after PCI for coronary heart disease.IL-6 and Kim-1 were positively correlated with the occurrence of CIN after PCI for coronary heart disease.IL-6 and Kim-1 have good diagnostic sensitivity and specificity for CIN after PCI for coronary heart disease.

ObjectiveTo evaluate the effect of Shengmaisan granules on myocardial fibrosis in chronic heart failure patients with Qi-Yin deficiency syndrome by cardiac magnetic resonance （CMR） imaging and serological indicators. MethodSixty-six chronic heart failure patients with Qi-Yin deficiency syndrome who visited the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine， Nanjing University of Chinese Medicine from October 2021 to January 2023 were selected. The patients were assigned into a control group （33 cases） and an observation group （33 cases） by the minimization random method. Both groups received standardized Western medicine treatment for heart failure. In addition， the control group was treated with placebo granules， and the observation group with Shengmaisan granules for a course of 6 months. The baseline data， clinical efficacy， TCM symptom scores， serological indicators ［high-sensitivity C-reactive protein （hs-CRP）， soluble growth stimulation expressed gene 2 protein （sST2）， pro-collagen Ⅲ N-terminal peptide （PⅢNP）， interleukin （IL）-6， IL-11， transforming growth factor-β₁ （TGF-β₁）］， echocardiography ［Left atrial diameter （LAD）， left ventricular end systolic diameter （LVEDs）， left ventricular end diastolic diameter （LVEDd）］ and CMR indicators ［left ventricular ejection fraction （LVEF）， myocardial extracellular volume fraction （ECV）， and longitudinal relaxation time （T1）］ were compared between the two groups. ResultFinally， 31 patients in the control group and 30 patients in the observation group were included. There was no significant difference in baseline data or indicators between the two groups before treatment. Compared with those before treatment， the scores of TCM symptoms （shortness of breath， fatigue， palpitations， spontaneous or night sweats， thirst/dry throat， feverish feeling in palms and soles， and edema in lower limbs）， total score of TCM symptoms， ECV， T1， inflammation/fibrosis indicators （hs-CRP， sST2， PⅢNP， IL-6， IL-11， and TGF-β₁） in observation group decreased （P<0.05， P<0.01）， and the scores of TCM symptoms （except feverish feeling in palms and soles）， T1， and inflammation/fibrosis indicators in the control group decreased （P<0.05， P<0.01）. After treatment， the observation group had lower scores of TCM symptoms （except feverish feeling in palms and soles and edema in lower limbs）， ECV， T1， and inflammation/fibrosis indicators than the control group （P<0.05， P<0.01）. After treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （80.65%， 25/31） in the control group （Z=2.976， P<0.01）. There was no significant difference in adverse reactions between the two groups during treatment. ConclusionFor patients with chronic heart failure with Qi-Yin deficiency syndrome， Shengmaisan Granules can alleviate the TCM symptoms， reduce inflammation， and inhibit myocardial fibrosis by regulating the TGF-β₁/IL-11 signaling axis.

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.

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 indentify the cognitive status of Chinese patients to acne and the influencing factors to theirs' cognitive status,so as to provide solid evidences for the prevention and treatment of acne.Methods A self-designed questionnaire was made to conduct this survey of 16,156 acne patients,who seeked to the treatment in the dermatological departments from 112 hospitals in China.The survey consisted of several parts,including the general status of patients,the patients' cognition of occurrence,development and risk factors of acne,whether the first choice was seeking treatment at the hospital when the patients had acne and the condition of selection of skin care products.The factors were analyzed,which could impact the cognition of the patients' behavior of treatment,how did the patients' cognition to influence their medical behavior and skin care as well as the consistency of assessment of the severity of acne by doctors and patients themselves.Results The acne patients studied had the best knowledge of "acne is a skin disease","it not only occurs in the period of adolescence" and "the disease can be prevented and cured",which accordingly accounted for 80.65％,69.16％ and 65.49％ of the total patients respectively.However,the awareness of acne patients to heredity,high sugar and dairy products as risk factors for acne was insufficient,which accounted for 48.72％,42.40％ and 18.25％ of the total patients,respectively.Gender,age,educational level,occupation and health knowledge were the main factors affecting the cognitive level of patients;the survey also found that men,patient with educational level of junior high or even lower educational condition,occupation of labor workers or farmers and patients were lack of health education with poor knowledge of the genetics and dietary were risk factors for acne;patients with age over 36 years or with mild illness had poor knowledge of dietary risk factors for acne;the difference was statistically significant (P＜0.05).The analysis of the influence of cognitive status on medical treatment behavior and skin care showed that the better the cognition,the higher the probability of patients would choose medical treatment as the first choice as well as choosing functional skin care products;the difference was statistically significant (P＜0.05).The consistency of assessment of the severity of acne by doctors and patients was poor (Kappa value ＜0.4),and the assessment of severity of acne by patients was more serious than doctors' assessment.Conclusions Patient's cognitive status will affect their medical behavior and skin care,and there is also a phenomenon that patients have a more serious assessment of their acne condition.It is suggested that health education for acne patients should be strengthened in clinical medicine so as to improve their knowledge of acne as well as preventing from acne effectively.

Objective The vertical mammoplasty which improves the breast morphology and reduces the operative scar has become the first selection of breast reduction.However,the nipple-and-areola complex (NAC) had the risk of necrosis in those severe patients.In this report,we performed the vertical reduction mammoplasty based on Wu'ringer's horizontal septum to reduce the NAC necrosis possibility.Methods Typical Lejourmosque-dome design was performed.The inferior part of glandular tissue and the skin were excised.The NAC was elevated to normal position based on Wu'ringer's horizontal septum.The breast morphology was modified with vertical scar left.Results 79 patients were operated.4 patients had unilateral breast reduction.4 breasts had partial wound dehiscence.They were treated conservatively with topical dressing.No complete NAC necrosis occurred.Conclusions The vertical reduction mammoplasty based on Wu'ringer's horizontal septum is a safe and effective procedure.The NAC necrosis risk is reduced.This method deserves to be recommended.

OBJECTIVE:To investigate the effects of polydatin on protein expression of MMP-9 and TIMP-1 in renal tissue of renal fibrosis model rats,and to investigate the mechanism of delaying renal fibrosis in rats. METHODS:A total of 40 rats were randomly divided into sham operation group(normal saline),model group(normal saline),polydatin group(100 mg/kg)and benazepril group(positive control,5 mg/kg). Except for sham operation group,renal fibrosis rat model was induced by unilateral ureteral obstruction in other groups. 1 h after surgery,each group was given relevant medicine intragastrically,once a day.After 4 weeks of consecutive treatment,the contents of β 2-microglobulin(β 2-MG)and N-acetyl-β-D-glucosaminidase(NAG)in urine, serum contents of BUN and Cr were detected in each group. HE staining was used to observe and score pathological changes of renal tissue in rats. Protein expressions of MMP-9 and TIMP-1 in renal tissue of rats were determined by immunohistochemistry. RESULTS:Compared with sham operation group,the contents of β2-MG and NAG in urine,serum contents of BUN and Cr were increased significantly in model group(P<0.05),and pathological score and protein expressions of MMP-9 and TIMP-1 were also increased significantly(P<0.01). Compared with model group,protein expression of MMP-9 in renal tissue were increased continuously in polydatin group and benazepril group(P<0.01);other indexes were decreased significantly(P<0.05 or P<0.01),and there was no statistical significance in each index between polydatin group and benazepril group(P>0.05). CONCLUSIONS:Polydatin can delay renal fibrosis,the mechanism of which may be associated with up-regulating protein expression of MMP-9,down-regulating protein expression of TIMP-1 and increasing the ratio of MMP-9/TIMP-1.

OBJECTIVE:To study the effects of maggot oil on the healing of rat with acute skin trauma and infection and its mechanism,in order and to provide reference for further development of maggot oil. METHODS:SD rats were randomly divided into normal group,model group,maggot oil group and Jingwanhong treatment group (positive control),with 70 mice in each group. Except for normal group,acute skin trauma and infection model was induced in other groups by smearing Staphylococus aureus suspension at the wound. After modeling,normal group and model group were given normal saline,and maggot oil group and Jingwanhong treatment group were given relevant medicine 0.3 mL/100 g,at 9:00 and 17:00,for consecutive 15 d. Wound and wound healing time of rats were observed in each group. The content of hydroxyproline in wound was determined in 10 rats of each group after 1,2,4,6,8 d of administration. The content of water in wound was determined after 2,4,6,8 d after administration. 2 h after last administration,the content of lysozyme,the levels of inflammatory factors (TNF-α,IL-6),the expression of NF-κB p65(in cytoplasm and nucleus)and p-IκB-α(in cytoplasm)protein were determined in 10 rats of each group. RESULTS:Compared with normal group,wound edema of model group was obvious,and wound healing time was(14.3±2.1)d. After 4,6,8 d of medication,the content of hydroxyproline in wound of rats was decreased significantly in model group (P<0.05 or P<0.01). After 2,4,6,8 d of medication,the content of water in wound was increased significantly in model group(P<0.01). After 15 d of medication,the serum contents of lysozyme,TNF-α and IL-6 in rats were increased significantly in model group (P<0.01). The expression of NF-κB p65 (in cytoplasm) in wound was decreased significantly (P<0.01),while the expressions of NF-κB p65 (in nucleus) and p-IκB-α(in nucleus) protein were increased significantly (P<0.01). Compared with model group,above indicators of administration groups were improved significantly (P<0.05 or P<0.01). CONCLUSIONS:Maggot oil could protect tissue injury induced by acute skin wound infection,promote wound healing. The possible mechanism might play anti-inflammatory effect through promoting collagen production,increasing lysozyme content,regulating NF-κB signal pathway.