Traditional Chinese medicine of Polygonum cuspidatum has been utilized in China for thousands of years. Its primary active compound, polydatin, exhibits a variety of pharmacological effects including the regulation of glucose and lipid metabolism, suppression of cough and asthma, as well as antibacterial and anti-inflammatory properties. However, conventional methods for polydatin production are inadequate to satisfy the market demand. This study aims to explore the green and efficient preparation of polydatin. With resveratrol as the substrate, we efficiently synthesized polydatin by using the triple mutant IGW (Y14I/I62G/M315W) of the glycosyltransferase UGT_BS based on a strategy of two-enzyme coupled with one-pot and realized the recycling of uridine diphosphate-glucose (UDPG). The conditions of the two-enzyme reaction were optimized. Under the conditions of 35 ℃, pH 8.0, IGW: AtSuSy1 activity ratio of 3:4, dimethyl sulfoxide (DMSO) volume fraction of 5%, uridine diphosphate (UDP) concentration of 0.10 mmol/L, and sucrose concentration of 0.6 mol/L, the conversion of 2 mmol/L resveratrol reached 80.6% within 1 h, and the proportion of polydatin was over 90%. This study achieved the recycling of UDPG via a two-enzyme coupling system and shortened the reaction time. At the same time, the fed-batch strategy was adopted, and the yield of polydatin reached 6.28 g/L after 24 h in the one-pot coupling reaction, which provided a new strategy for green and efficient preparation of polydatin.
Stilbenes/chemistry* ; Glucosides/biosynthesis* ; Resveratrol ; Fallopia japonica/chemistry* ; Glycosyltransferases/genetics*

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 explore the clinical features and treatment of pyoderma gangrenosum (PG). Methods: A retrospective observational study was conducted. From January 2012 to July 2021, 25 patients with PG who met the inclusion criteria were admitted to Beijing Fucheng Hospital, including 16 males and 9 females, with the age of onset of disease being 14 to 75 years. Among them, the classification of PG identified 17 cases of ulcerative type, 6 cases of pustular type, 1 case of proliferative type, and 1 case of bullous type. Six patients were accompanied with systemic diseases, while 19 patients were not accompanied with systemic diseases. At the same time of systemic treatment with glucocorticoids, dressing changes or surgical skin grafting was performed on the wounds. The results of laboratory and histopathological examinations, the overall curative effects and follow-up of patients, the wound healing time of patients with negative and positive microbial culture results of wound secretion specimens, and the curative effects of patients with and without systemic diseases were analyzed. Results: The results of blood routine examination of 19 patients were abnormal, and all the immunological indexes were normal in all the patients; the microbial culture results of wound secretion specimens were positive in 14 patients; and the histopathological examination results of ulcer boundary tissue in 15 patients with rapid wound progress were mainly local tissue inflammatory changes. The wounds were cured in 17 patients, mostly healed in 7 patients, and not healed in 1 patient. After one-year's follow-up, the PG in 3 patients relapsed due to self-discontinuation of medication after discharge, and the wounds were healed gradually after adjustment of medication, while the remaining patients had no relapse. The days of wound healing in 14 patients with positive microbial culture results of wound secretion specimens were 21-55 days, and the days of wound healing in 11 patients with negative microbial culture results in wound secretion specimens were 20-54 days. In the 6 patients with systemic diseases, the wounds of 3 patients were cured, and the wounds of the other 3 patients were mostly healed. In the 19 patients without systemic diseases, the wounds of 14 patients were cured, the wounds of 4 patients were mostly healed, and the wound of 1 patient was not healed. Conclusions: The laboratory examination and pathological manifestations of patients with PG lacks characteristics, and their clinical manifestations are rich and diverse, thus PG can be easily misdiagnosed. The glucocorticoids combined with immunosuppressive therapy have good effects on PG. Surgical intervention can be performed on the wounds. Specifically, excessive debridement is not recommended in the acute phase, but skin grafting can be performed in the contraction phase.
Administration, Cutaneous ; Adolescent ; Adult ; Aged ; Female ; Glucocorticoids ; Humans ; Male ; Middle Aged ; Pyoderma Gangrenosum/therapy* ; Skin Transplantation ; Wound Healing ; Young Adult

Objective:To evaluate the diagnostic value of coronary angiography-based fractional flow reserve(caFFR)versus a wire-based fractional flow reserve(FFR)in elderly patients with stable ischemic heart disease.Methods:A total of 168 patients(186 vessels)who underwent a pressure wire(PW)-based FFR measurement from Jan.2015 to Dec.2019 in Beijing hospital were enrolled and analyzed retrospectively.Coronary angiography images and matched steady-state aortic pressure of patients were sent to the core laboratory for caFFR measurement under the blind method.All patients were divided into the non-elderly group(<65 years, n=93)and the elderly group(≥65 years, n=75). The diagnostic value of caFFR was evaluated by using the wire-based FFR cut-off value of ≤0.80 as the reference standard.The correlation and consistency of caFFR and wire-based FFR were analyzed, and compared between the non-elderly and elderly groups.Results:The caFFR had a good correlation and consistency with wire-based FFR in the elderly group( r=0.796, P<0.01). In non-aged versus elderly groups, diagnostic accuracy of caFFR was 91.9% versus 93.1%, diagnostic sensitivity of caFFR was 91.8% vs.93.2%, diagnostic specificity of caFFR was 92.3% vs.93.0%, all P>0.05.The area under the receiver-operating characteristic curve of caFFR had no significant difference between the non-elderly and elderly patients(0.964 vs.0.972, Z=0.00823, 95% CI: -0.037-0.052, P>0.05). Conclusions:The caFFR has a good diagnostic correlation and consistency with wire-based FFR in the elderly group, and caFFR's diagnostic performance in the elderly is similar to that in the non-elderly patients.

Objective:To investigate the role and mechanism of metformin in algesia of rats with type 2 diabetic neuropathic pain (DNP).Methods:Eighty sprague-dawley rats were randomly divided into normal control group ( n=15) and high-fat and high-glucose group ( n=65); normal diet and high-fat and high-sugar diet were given, respectively; before and 8 weeks after feeding, the body mass of rats and fasting blood glucose level were recorded, fasting insulin level was detected by ELISA, and insulin sensitivity index (ISI) was calculated. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) 8 weeks after feeding (baseline values) were measured in the high-fat and high-glucose group; after 12 h of fasting, intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) was performed; 3 d after fasting, blood glucose was measured; 14 d after STZ injection, body mass was recorded and MWT and TWL were measured again: when MWT and TWL were ≤85% baseline values, it was defined that DNP model was successfully established ( n=45); and the left were into the diabetic painless group ( n=15). The rats with successful DNP were randomly divided into DNP group, DNP+vehicle group and DNP+metformin group ( n=15); 14 d after STZ injection, rats in the DNP+metformin group were given intraperitoneal injection of metformin (200 mg/kg) once daily for 14 consecutive d; DNP group did not accept any treatment, and rats in DNP+vehicle group were intraperitoneally injected with same amount of normal saline. MWT and TWL of all rats were measured 14 d after STZ injection, and 3, 7, 14 and 21 d after metformin injection. The expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were detected by ELISA 7, 14 and 21 d after metformin injection. The fluorescence intensity of ionized calcium binding adaptor molecule-1 (Iba-1) in the spinal cord was detected by immunofluorescence staining, and the expression levels of Toll-like receptor 4 (TLR4), nuclear transcription factor (NF)-κB, phosphorylated (p)-NF-κB, adenylate activated protein kinase (AMPK), p-AMPK, and peroxisome proliferator activated receptor-γ coactivator (PGC)-1α in the spinal cord were detected by Western blotting 21 d after metformin injection. Results:(1) After 8 weeks of feeding, the body mass of rats in the high-fat and high-glucose group was significantly higher than that in the normal control group ( P<0.05); and the body mass of rats in the high-fat and high-glucose group was statistically lower than that in the normal control group 14 d after STZ injection ( P<0.05). Three d after STZ injection, the blood glucose level in high-fat and high-glucose group was significantly higher than that in normal control group ( P<0.05). After 8 weeks of feeding, the insulin level of high-fat and high-glucose group was statistically higher than that of normal control group, and the ISI in the high-fat and high-glucose group was significantly decreased as compared with that in the normal control group ( P<0.05). (2) As compared with those in the normal control group and diabetic painless group, MWT and TWL of DNP group and DNP+vehicle group were significantly decreased at each time point ( P<0.05). Three, 7, 14 and 21 d after metformin injection, MWT and TWL in DNP+metformin group were significantly increased as compared with those in DNP group and DNP+vehicle group ( P<0.05). (3) Seven, 14, and 21 d after metformin injection, the levels of IL-6, IL-1β and TNF-α in the spinal cord of rats in the DNP group and DNP+vehicle group were significantly increased as compared with those in the normal control group and diabetic painless group ( P<0.05); as compared with those in the DNP group and DNP+vehicle group, the levels of IL-6, IL-1β and TNF-α in the spinal cord of DNP+metformin group were significantly decreased ( P<0.05). (4) As compared with normal control group and diabetic painless group, the fluorescence intensity of Iba-1 and number of Iba-1 positive cells in the spinal cord tissues of DNP group and DNP+vehicle group were significantly increased ( P<0.05); while the fluorescence intensity of Iba-1 and number of Iba-1 positive cells in spinal cord tissues of DNP+metformin group were significantly decreased as compared with those in the DNP group and DNP+ vehicle group ( P<0.05). (5) As compared with those in the normal control group and diabetic painless group, the TLR4 and p-NF-κB protein expressions and p-NF-κB/NF-κB values in the spinal cord tissues of DNP group and DNP+vehicle group were significantly increased ( P<0.05); while those in the spinal cord tissues of DNP+metformin group were significantly decreased as compared with those in the DNP group and DNP+vehicle group ( P<0.05). As compared with those in the normal control group and diabetic painless group, the PGC-1α protein expression and p-AMPK/AMPK values in the spinal cord tissues of DNP group and DNP+vehicle group were significantly decreased ( P<0.05); while those in the spinal cord tissues of DNP+metformin group were significantly increased as compared with those in the DNP group and DNP+vehicle group ( P<0.05). Conclusion:Metformin, by activating AMPK/PGC-1α signaling pathway, may inhibit the TLR4/NF-κB expression, reduce the activation of microglia and the expressions of pro-inflammatory factors, and thus alleviate DNP.

Objective: To understand the homosexual behavior and related factors among married MSM in Mianyang city. Methods: Between January and October in 2017, a snowball sampling method was adopted to carry out cross-sectional survey through questionnaires plus HIV testing among those MSM in Mianyang city. Logistic regression model was used to analyze homosexual behaviors and related factors among married MSM under study. Statistical analysis was used by EpiData 3.1 and SPSS 19.0 software. Results: A total of 234 MSM participated in this survey. The overall rate of homosexual behavior in these married MSM appeared as 94.9% (222/234). Rate of having anal sex behavior was 94.4% (221/234) in the past 6 months, with rate of condom use as 57.9% (128/221). HIV positive rate was 8.1% (18/222). As for the motives for homosexual behavior after marriage, 87.8% (195/222) were driven by feelings of love, 12.2% (27/222) due to 'releasing pressure’. Proportion of male sex partners would include occasional sex partners (62.2%, 138/222), stable male sex partners (26.1%, 58/222) and stable boyfriends (11.7%, 26/222). Factors from logistic regression analysis showed that homosexual behaviors were related to the factors including education level of senior high school or above vs. education level of junior middle school or below (OR=3.65, 95%CI: 1.33-9.98); local residency over one year vs. the ones having local residency less than one year (OR=23.28, 95%CI:1.67-324.89); having 10 or more friends in the MSM community vs. having below 10 friends in MSM community (OR=4.15, 95%CI: 1.28-13.43); without sex pleasure with spouse vs. having sex pleasure with spouse (OR=3.25, 95%CI: 1.22-8.62); having 2 or more anal sex partners in the past 6 months vs. having less than 2 anal sex partners in the past 6 months (OR=0.28,95%CI: 0.09-0.81). Conclusions The rate of homosexual behavior and HIV positive rate were high among MSM in Mianyang city. Homosexual behaviors after marriage were influenced by multiple factors among MSM. The motives of homosexual behavior after marriage were driven by feelings of love, the related factors were education level of senior high school or above, local residency over one year, having 10 or more friends in the MSM community and without sex pleasure with spouse. As for the motives of these behaviors was caused by releasing pressure, the related factors was having more than 2 anal sex partners.

Objective To evaluate the clinical impact of percutaneous coronary intervention (PCI)on prognosis in elderly patients(≥70 years old)with coronary artery chronic total occlusion (CTO). Methods A total of 445 consecutive patients with a angiography-confirmed CTO lesions registered from January 2011 to December 2013 were divided into the elderly group(≥70 years)and the non-elderly group(< 70 years).The primary endpoints measured were defined as the composite outcomes of hospitalization due to angina,re-infarction,heart failure,repeat re-vascularization,and cardiac death at 36 months follow-up. Results The elderly group included 200 patients(44.9%) and the non-elderly group included 245 patients(55.1%).During the follow-up,the proportions of coronary lesion were significantly higher in the elderly group with left main(LM)disease(45, 22.5%),three-vessel disease(166,83.0%)and J-CTO score≥2(64,32.0%)than in the non-elderly group with diseases of LM,three-vessel,and J-CTO score ≥ 2〔(34,13.9%);(180,73.5%);(57, 23.3%),respectively〕(χ2 =5.607,5.782,4.243;P=0.018,0.016,0.039).T he ratio of the patients undergoing PCI-reperfusion therapy of CTO was higher in non-elderly group(109/275,39.6%)than in elderly group(53/222,23.9%)(χ2 =13.891,P<0.001),while CTO PCI success rate was similar between the two groups(38 patients,71.7% vs.90 patients,82.6%,χ2 = 2.541,P= 0.111).The elderly group versus non-elderly group showed that the 3-year cardiac mortality rate was 12.5%(25 patients)versus 3.3%(8 patients)(χ2 =13.677,P<0.011),and the incidence rate of 3-year primary endpoint was 31.5%(63 patients)versus 22.9%(56 patients)(χ2 =4.199,P=0.040).Among the elderly group,patients without CTOs re-vascularized by PCI had a greater tendency toward higher risk of hospitalization due to angina,re-infarction,heart failure,or repeat re-vascularization than patients with CTOs re-vascularized by PCI(34/149,22.8% vs.3/33,9.1%,χ2 =3.143,P=0.076),while they had comparable incidence of 3-year cardiac death(19/149,12.8% vs.5/33,15.2%,χ2 = 0.007,P=0.933).Multivariate analysis revealed that after adjusting for baseline and procedure differences,LM combined with three vessel disease(OR= 3.804,95% CI:1.274 to 11.356,P= 0.017)remained an independent predictor for 3-year cardiac mortality in elderly patients with CTOs. Conclusions Elderly patients with CTO have mostly a serious coronary artery disease and a poor prognosis.Although CTO is re-vascularized by PCI,long-term clinical outcome seems not more to be improved in elderly patients with CTOs.LM combined with three-vessel disease might be an independent predictor for 3-year cardiac mortality in elderly CTO patients.

Objective To investigate the prevalence and risk factors for atherosclerotic renal artery stenosis (ARAS) in elderly patients with refractory hypertension.Methods Two hundred and eight elderly patients with a mean age of (68.3±4.9)years (53.8％ in men) diagnosed with refractory hypertension were recruited in this retrospective study from January 2010 to January 2017 in Beijing hospital.Fifty of the 208 patients with ultrasonography-suspected renal artery stenosis received renal arteriography and 39 were confirmed as renal artery stenosis.Renal artery stenosis was defined when stenosis located in at least one of renal arteries and only if the stenosis equal or over 50％.The prevalence of ARAS was calculated.Besides,univariate and final multivariate Logistic regression analyses were conducted to detect independent risk factors for development of ARAS.Results Thirty-nine of 208 patients (18.8％) were confirmatively diagnosed as ARAS.Although univariate Logistic regression showed that diabetes,coronary heart disease,renal insufficiency,and peripheral artery disease (P=0.034,0.040,0.022,and 0.030) might be risk factors for ARAS,a multivariate regression analysis demonstrated that only the peripheral artery disease (OR=3.218,P＜0.01) and renal insufficiency (OR=3.827,P＜0.01) were independent risk factors for ARAS.Conclusions Renal angiography should routinely be performed in refractory hypertension patients with renal insufficiency or peripheral artery disease to identify ARAS in time.

Objective To analyze the safety and efficacy of coronary rotational atherectomy in elderly patients with coronary heart disease.Methods A total of 107 consecutive patients with coronary artery disease receiving rotational atherectomy from January 2012 to December 2016 were retrospectively analyzed.Patients were divided into an ≥75 years group(n=44)and a ＜75 years group (n=63).We compared the characteristics of rotational atherectomy,peri-procedural complications,instant procedure success rates and 1-year cardiovascular events,including angina,re-infarction,hospitalization due to heart failure,repeat revascularization and cardiac death.Results There was no significant difference in the target coronary vessel,reference vessel diameter,maximal diameter of the burr and ratio of maximal diameter of the burr to reference vessel diameter between the two groups(all P＞0.05).Compared with ＜75 years patients,more ≥75 years patients used 2 burrs(10 cases or 22.7％ vs.4 cases or 6.3％,P =0.013),while there was no significant difference in terms of burr size,rotational time,maximal rotational speed,pre-and post-dilation pressure between the two groups (all P＞0.05).The incidence of peri-procedural complications had no significant difference between the ≥75 years group and the ＜75 years group(8 cases or 18.2％ vs.13 cases or 20.6％,P =0.753).One case of burr entrapment occurred in each group with successful retrieval.The procedure success rate was 96.8％(61 cases)in the ＜75 years group and 100％ in the ≥75 years group(P=0.640).No acute or sub-acute stent thrombosis or urgent coronary artery bypass graft occurred in the two groups during hospitalization.No cardiac death occurred in either group.Conclusions Coronary rotational atherectomy is effective and safe in elderly patients with coronary disease with a high instant procedure success rate.

Objective: To study the prognostic impact of chronic total occlusion (CTO) on non-infarct-related artery (non-IRA) in patients of acute ST-elevation myocardial infarction (STEMI) with emergent primary percutaneous coronary intervention (PCI).
Methods: In this prospective study, a total of 185 consecutive acute STEMI patients received early stage primary PCI in our hospital from 2010-01to 2011-06 were enrolled. The patients were divided into 2 groups:non-CTO group, n=160 and CTO group, n=25. The patients were followed-up for 1 year and the primary endpoint events included the hospitalization for angina, re-MI, heart failure or revascularization and cardiac death.
Results: ①There were more patients with diabetes and three vessel disease in CTO group than those in non-CTO group (40.0%vs 20.0%, P=0.049) and (68.0%vs 36.3%, P=0.003);LVEF in CTO group was lower than non-CTO group (40.0 ± 20.1%vs 51.3 ± 15.3%, P<0.05).②The cardiac mortalities at 6-month and 1-year followed-up period were higher in CTO group than those in non-CTO group (26.3%vs 6.1%, P=0.013) and (31.6%vs 8.4%, P=0.010);1-year primary endpoint events were higher in CTO group (52.6%vs 16.8%, P=0.001). ③Multivariate regression analysis revealed that non-IRA combining CTO (HR=3.889, 95%CI 1.239-4.206, P=0.020), cardiac shock (HR=3.229, 95%CI 2.760-3.725, P=0.012) and three vessel disease (HR=2.008, 95%CI 1.549-3.372, P=0.040) were the independent predictors for 1-year mortality in patients of acute STEMI with primary PCI.
Conclusion: Non-IRA combining CTO in STEMI patients with primary PCI are usually having poor prognosis.