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 discuss the clinical safety,feasibility and efficacy of transcatheter arterial infusion chemotherapy(TAI)combined with lipiodol chemoembolization in the treatment of advanced colorectal cancer(CRC).Methods The clinical data of 37 patients with advanced CRC,who received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University of China between June 2016 and December 2022,were retrospectively analyzed.The clinical efficacy was evaluated,the progression-free survival(PFS)and the serious complications were recorded.Results A total of 55 times of TAI combined with lipiodol chemoembolization procedures were successfully accomplished in the 37 patients.The mean used amount of lipiodol emulsion was 2.9 mL(0.8-10 mL).No serious complications such as bleeding and intestinal perforation occurred.The median follow-up time was 24 months(range of 3-48 months).The postoperative one-month,3-month,6-month and 12-month objective remission rates(ORR)were 67.6%(25/37),67.6%(25/37),64.9%(24/37)and 56.8%(21/37)respectively,and the postoperative one-month,3-month,6-month and 12-month disease control rates(DCR)were 91.9%(34/37),91.9%(34/37),89.2%(33/37)and 81.1%(30/37)respectively.The median PFS was 16 months(range of 2-47 months).As of the last follow-up,22 patients survived and 15 patients died of terminal stage of tumor.Conclusion Preliminary results of this study indicate that TAI combined with lipiodol chemoembolization is clinically safe and effective for advanced CRC,and it provide a new therapeutic method for patients with advanced CRC.

Objective To investigate the efficacy and safety of interventional therapy for bronchopleural fistula(BPF).Methods A total of 172 patients with confirmed BPF were treated with continuous negative pressure drainage(CNPD)and/or airway stent occlusion therapy.The clinical data were collected,and its effectiveness and safety were analyzed.Results In 5-7 days after interventional treatment,the pneumonia severity index(PSI)decreased significantly,and successful drainage was achieved in 166 patients(96.5％).One month after interventional therapy,the lung volume was remarkably increased.The median clinical healing time of interventional therapy was 9.0 months(95％CI=6.18-1 1.83).Multivariate analysis of the Cox proportional hazards model showed that the diagnosis time(HR=0.53,95％CI=0.38-0.74,P＜0.01)and fistula size(HR=0.74,95％CI=0.55-0.99,P=0.04)were significantly correlated with the clinical healing time.Conclusion For the treatment of BPF,CNPD and/or airway stent occlusion has several advantages such as accurate operation,minimally invasive,safe and effective.It can quickly improve the symptoms and quality of life,and prolong survival,therefore,it is worthy of clinical promotion and application.(J Intervent Radiol,2024,33:641-645)

Objective:To evaluate left ventricular structural and functional abnormalities and vascular calcification in kidney transplant (KT) recipients, explore their influencing factors and examine the effects of mineral and bone disorders.Methods:From January 2017 to December 2019, retrospective analysis was performed for 292 KT recipients. Biochemical markers of bone metabolism, bone mineral density (BMD), left ventricular hypertrophy (LVH), left ventricular ejection fraction (LVEF), left ventricular diastolic function, coronary artery calcification (CAC) score and thoracic aortic calcification (TAC) score were assessed. Linear regression and binary Logistic regression analyses were employed for evaluating the influencing factors of cardiovascular parameters and the influence of abnormal mineral and bone metabolism.Results:Postoperative abnormalities in mineral and bone disorders were manifested mostly as hypercalcemia (8.9%, 26/292), hypophosphatemia (27.1%, 79/292), low 25-hydroxyvitamin D (25(OH)vitD) (67.0%, 196/292), hyperparathyroidismhigh parathyroid hormone (PTH) (50.6%, 148/292), elevated bone turnover markers and bone loss rate of 25%-30%. The prevalence of LVH, LVEF<50%, left ventricular diastolic dysfunction, high CAC score and high TAC score were 39.9%(116/292), 0%, 13.1%(38/292), 17.3%(50/292) and 39.9%(116/292) respectively. The results of multivariate analysis indicated that LVH was correlated positively with hypertension and serum calcium (Ca) (95% CI: 1.242-28.080, P=0.026; 95% CI: 1.714-277.584, P=0.018); LVEF was correlated positively with lumbar vertebrae BMD (95% CI: 0.000 1-0.005 5, P=0.041); Left ventricular diastolic dysfunction was correlated positively with age, diabetes and parathyroid hyperplasia/nodules (95% CI: 1.050-1.176, P<0.001; 95% CI: 2.118-43.813, P=0.003 and 95% CI: 1.419-9.103, P=0.007); High CAC score was correlated positively with recipient age and dialysis time (95% CI: 1.036-1.160, P=0.001; 95% CI: 1.009-1.041, P=0.002); High TAC score was correlated positively with age (95% CI: 1.095-1.215, P<0.001). Correlation analysis indicated that TAC was correlated positively with serum Ca ( r=0.233, P=0.003), bone-specific alkaline phosphatase (BALP)( r=0.325, P<0.001) and type Ⅰ collagen cross-linked N-terminal peptide (NTX)( r=0.204, P=0.011) and negatively with femoral neck BMD ( r=0.194, P=0.017). Conclusions:There is a high prevalence of left ventricular structural and functional abnormalities and vascular calcification. It is closely correlated with mineral and bone disorders.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Objective:To investigate the influencing factors, periprocedural complications, and long-term outcomes of successful recanalization after endovascular treatment in patients with non-acute symptomatic internal carotid artery occlusion.Methods:Patients with non-acute internal carotid artery occlusion received endovascular treatment in the Nanjing Stroke Registration System between January 2010 and December 2021 were retrospectively enrolled. Clinical endpoint events were defined as successful vascular recanalization, periprocedural complications (symptomatic embolism and symptomatic intracranial hemorrhage), neurological function improvement, and recurrence of ipsilateral ischemic events. Multivariate logistic regression analysis was used to investigate the independent influencing factors of successful vascular recanalization. Cox proportional hazards regression analysis was used to investigate the correlation between endovascular treatment outcomes and neurological function improvement, as well as ipsilateral ischemic cerebrovascular events. Results:A total of 296 patients were included, of which 190 (64.2%) were successfully recanalized. Multivariate logistic regression analysis showed that symptoms manifest as ischemic stroke (odds ratio [ OR] 3.353, 95% confidence interval [ CI] 1.399-8.038; P=0.007), the time from the most recent symptom onset to endovascular therapy within 1 to 30 d ( OR 2.327, 95% CI 1.271-4.261; P=0.006), proximal conical residual cavity ( OR 2.853, 95% CI 1.242-6.552; P=0.013) and focal occlusion (C1-C2: OR 3.255, 95% CI 1.296-8.027, P=0.012; C6/C7: OR 5.079, 95% CI 1.334-19.334; P=0.017) were the independent influencing factors for successful vascular recanalization. Successful recanalization did not increase the risk of symptomatic intracranial hemorrhage within 7 d after procedure (3.2% vs. 0.9%; P=0.428). The median follow-up time after procedure was 38 months. Cox proportional hazards regression analysis showed that after adjusting for confounding factors, successful recanalization was significantly associated with postprocedural neurological improvement (hazard ratio 1.608, 95% CI 1.091-2.371; P=0.017), and significantly reduced the risk of recurrence of long-term ischemic events (hazard ratio 0.351, 95% CI 0.162-0.773; P=0.010). Conclusion:In patients with non-acute internal carotid artery occlusion, successful endovascular recanalization can effectively reduce the risk of long-term ischemic events without increasing the risk of symptomatic intracranial hemorrhage.

Squamous cell carcinoma, which originates from squamous epithelium or tissue that undergoes squamous epithelial metaplasia, is one of the most common pathological types of solid human carcinoma. Although squamous cell carcinoma can occur in different anatomical locations, its pathogenesis has commonalities and distinctive features. Genetic mutations and abnormal expression of squamous differentiation markers, epigenetic modifications regulating target gene expression, and tumor microenvironment inducing immune escape of cancer cells are all involved in the development of squamous cell carcinoma. At present, great progress has been made in the research on the pathogenesis of squamous cell carcinoma. This article, combined with relevant research in recent years, reviews the pathogenesis of squamous cell carcinoma in terms of genome changes, epigenetic changes, non coding RNA regulation, tumor microenvironment changes and risk factor induction, so as to provide reference for the prevention and treatment of squamous cell carcinoma.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To investigate predictive factors for successful endovascular recanalization in patients with non-acute symptomatic internal carotid artery occlusion (SICAO), to develop a decision tree model using the Classification and Regression Tree (CART) algorithm, and to evaluate the predictive performance of the model.Methods:Patients with non-acute SICAO received endovascular therapy at 8 comprehensive stroke centers in China were included retrospectively. They were randomly assigned to a training set and a validation set. In the training set, the least absolute shrinkage and selection operator (LASSO) algorithm was used to screen important variables, and a decision tree prediction model was constructed based on CART algorithm. The model was evaluated using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and confusion matrix in the validation set.Results:A total of 511 patients with non-acute SICAO were included. They were randomly divided into a training set ( n=357) and a validation set ( n=154) in a 7:3 ratio. The successful recanalization rates after endovascular therapy were 58.8% and 58.4%, respectively. There was no statistically significant difference ( χ2=0.007, P=0.936). A CART decision tree model consisting of 5 variables, 5 layers and 9 classification rules was constructed using the six non-zero-coefficient variables selected by LASSO regression. The predictive factors for successful recanalization included fewer occluded segments, proximal tapered stump, ASITN/SIR collateral grading of 1-2, ischemic stroke, and a recent event to endovascular therapy time of 1-30 d. ROC analysis showed that the area under curve of the decision tree model in the training set was 0.810 (95% confidence interval 0.764-0.857), and the optimal cut-off value for predicting successful recanalization was 0.71. The area under curve in the validation set was 0.763 (95% confidence interval 0.687-0.839). The accuracy was 70.1%, precision was 81.4%, sensitivity was 63.3%, and specificity was 79.7%. The Hosmer-Lemeshow test in both groups showed P>0.05. Conclusion:Based on the type of ischemic event, the time from the latest event to endovascular therapy, proximal stump morphology, the number of occluded segments, and the ASITN/SIR collateral grading constructed the decision tree model can effectively predict successful recanalization after non-acute SICAO endovascular therapy.

AIM: To investigate the protective effect of ferulic acid on palmitic acid-induced lipotoxicity in HepG2 cells and to explore its potential molecular mechanisms. METHODS: HepG2 cells were induced by palmitic acid to establish a lipotoxicity model, while ferulic acid was added prior to palmitic acid treatment. Lactate dehydrogenase (LDH) was used to detect cell damage. Methyl azozole trace enzyme reaction is used for 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) was employed to detect cell viability. The molecular mechanisms of the protective effect of ferulic acid was analyzed by Western Blotting. RESULTS: There was no cytotoxic effect of different concentrations of ferulic acid (25, 50, 100, 200 μmol/L) treatment on HepG2 cells (P>0.05). Ferulic acid intervention significantly inhibited palmitic acid-induced cell death and improved palmitic acid-induced reduction of cell mitochondrial membrane potential (P<0.05). The activation of p38 significantly enhanced palmitic acid-induced hepatocellular lipotoxicity (P<0.05), while inhibition of p38 significantly improved palmitic acid-induced cell damage (P<0.05). In addition, ferulic acid significantly inhibited the upregulation of p38 phosphorylation by palmitic acid treatment (P<0.05). p38 activator exposure blocked the protective effect of ferulic acid on lipotoxicity (P<0.05). CONCLUSION: Ferulic acid effectively improves hepatocellular injury induced by lipotoxicity.The inhibition of p38 signaling pathway is potentially involved in its protective effect. Ferulic acid may be an effective factor in the prevention and treatment of liver disease with lipotoxicity as a major pathological characteristic.