In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1β, which was achieved through the suppression of the NLRP3 pathway.
Humans ; Hypoglycemic Agents/pharmacology* ; Circular Dichroism ; Cytokines ; Glucose ; Hep G2 Cells ; Insulin Resistance

Objective:To establish a calculation model for the operational efficiency and resource allocation of clinical departments in hospitals, for references for hospitals to optimize resource allocation.Methods:The informations including hospitalization time, nursing grade, etc. of inpatients admitted by 32 clinical departments in a tertiary public hospital from January to December in 2021 were extracted. A data envelopment analysis method was conducted on the operation efficiency and input edundancy of the departments. The K-means algorithm was used to divide inpatients into 3 categories according to the level of medical workload. Taking the numbers of doctors, nurses and beds as the input indicators, and the numbers of patients in the 3 categories as the output indicators, a BCC model 1 was established to evaluate the efficiency of resources invested by clinical departments into professional human value. At the same time, a BCC model 2 was established with the total number of patients admitted and medical income as the output indicators to evaluate the efficiency of resources invested by clinical departments into economic benefits.Results:A total of 38 147 inpatients were enrolled. There were 14 departments with overall technical efficiency (OTE) =1.000 in the BCC model 1, 10 departments with OTE=1.000 in the BCC model 2, and 8 departments with OTE=1.000 in the 2 models. As for the input redundancy, 6 departments had high input redundancy in the BCC model 1, 11 departments had high input redundancy in the BCC model 2, and 4 departments had high input redundancy in both models.Conclusions:The model established by this study could effectively evaluate the operational efficiency and input redundancy of clinical departments, identify departments with high workload and low economic benefits, and provide reference for the rational allocation of medical resources in hospitals.

Objective:To explore the clinical efficacy of treating external iliac artery dissection in renal transplantation by artificial vascular replacement.Methods:Four sudden intraoperative cases of external iliac artery dissection were selected.After removing vascular sutures, intimal arterial peeling blocked external iliac artery( n=3)and transplanted renal artery( n=1). Artificial vascular replacement of external iliac artery was performed using artificial vessels made from puffed polytetrafluoride ethylene(ePTFE). Secondary perfusion was performed in four transplanted kidneys for anastomosing with internal iliac artery. Results:One patient regained normal renal function within 1 week post-operation.Two cases had delayed graft function.Another case had delayed graft function plus acute rejection.After hemodialysis, renal function normalized at 2-3 weeks post-operation.During a follow-up period of(0.5-5.0)years, transplanted kidney function remained stable, blood supply, skin temperature and movement of operated lower extremities normalized.Conclusions:The incidence of vascular dissection of external iliac artery is not high during renal transplantation.However, the disease has a rapid and dangerous progression.The consequences of delayed intervention are quite serious.Treating external iliac artery dissection with renal transplantation may achieve satisfactory clinical outcomes.

Objective:To explore the feasibility and optimization effect of modifying the Henry Ford Hospital (HFHS) RapidPlan model for stereotactic body radiation therapy planning based on local requirements.Methods:The following changes were made based on Henry Ford Health System(HFHS) Rapid Plan Lung SBRT model, taking the latest clinical guideline evidence and local clinical practice into account: Internal gross target volume(IGTV) and organ at risk(OAR) structure, lung, were added and set corresponding parameters.The upper value of planning target volume (PTV) was adjusted from 109% to 125%. The original training library was replaced with 73 local historical simultaneous integrated boosting plans, and statistical verification and outlier cleaning of the initial trained model were performed using Model Analytics software. Totally 10 cases not included in the model library were selected for independent verification, and automatic optimization result of the models before and after modifying were compared under the same beam condition. The following dosimetric parameters were compared after target dose normalization: conformal index (CI) of target volume, the mean doses, maximum doses and dose-volume parameters of OARs.Results:The " tail" of the PTV′s DVH and the " shoulder" and " tail" of the IGTV′s DVH of model M (local) validation plan (M (local)_P) performs higher than the original model HFHS (HFHS_P). The PTV_CI (1.07±0.13) of M local_P were significantly smaller than HFHS_P (1.25±0.24) ( Z=-2.497, P<0.05). Except for Heart_ D15 cm 3 and Heart_ Dmax, most of the M local_P dosimetric parameters of OARs were lower than HFHS_P, and the standard deviation was smaller. However, the difference of between two plans was no more than 3.06%. 10 HFHS_P plans don′t satisfy dose parameters requirement, two of which PTV_CI values are 1.52 and 1.74, far beyond the clinically acceptable range. Conclusions:Commercial model HFHS could be localized by replacing training library and adjusting parameters. Moreover, plans optimized by the modified model are local clinical acceptable in the aspects of target volume conformity and hotspots, and have a better performance in terms of OAR sparing and plan consistency.

Objective:To analyze and compare the radiation dose and image quality of kilo-voltage cone beam CT systems on different Varian accelerator platforms, providing data to support clinical decisions on selecting optimal protocols for image-guided radiotherapy based on cost-effective ratio (image quality / radiation dose).Methods:The radiation dose and image quality of various CBCT systems and scanning protocols on Varian Edge, Truebeam and ix (new and old) LINACs were obtained using a CT dose index (CTDI) phantom combined with a CT ionization chamber and a Catphan604 phantom, respectively. Figure of merit (FOM) was used to evaluate the cost-effective ratio of the image guidance schemes.Results:Considerable inter-system varieties of FOMs were observed, varying from 0.65 (Image Gently-full trajectory) to 48.46 (Image Gently-half trajectory). The inter-protocol varieties were also large, where the mean±SD was 22.14±13.47.Conclusions:Considering the explicit inter-system and inter-protocol varieties, it is clinically favorable to evaluate the image guidance schemes based on machine-specific measurement. For instance, parameters and equipment with low CTDI w can be beneficial for dose-sensitive patients. High CNR regimen favors patients with high image quality requirements. For ordinary patients, cost-effective ratio in terms of FOM can be very helpful to guide the decision-making of clinical image-guided radiotherapy.

Objective:To verify the accuracy of the International Warfarin Pharmacogenetics Consortium(IWPC)model, identify the effects of genetic and clinical factors on steady-state doses of Warfarin, and establish a Warfarin dose prediction model for the Han-Chinese population aged 75 years and over under the guidance of pharmacogenetics.Methods:A total of 544 Han-Chinese patients receiving Warfarin therapy for atrial fibrillation were divided into two groups: those aged 75 years and over(n=164)and those aged below 75 years(n=380). Data for the whole population and the two age groups were each substituted into the IWPC prediction model for accuracy verification.Demographic and clinical characteristics of 164 patients aged 75 years and over were recorded, and the genotypes of CYP2 C9 and VKORC1- G1639 A were detected by polymerase chain reaction.A new pharmacogenetic-guided dosing algorithm for the elderly was obtained by stepwise multiple linear regression.The accuracy of the new model was compared with that of the IWPC model. Results:The predictive accuracy of IWPC for steady-state dosing of warfarin was 35.47% in all subjects, 33.75% in 164 subjects aged below 75 years, and only 28.70% in subjects aged 75 years and over, respectively.In 164 subjects aged 75 years and over, three genotypes of *1/*1, *1/*3 and *1/*2 were detected in CYP2 C9 polymorphism, and the CYP2 C9*1/*1 genotype was the most common one, with a frequency of 87.80%(144/164), followed by the CYP2 C9*1/*3 genotype, at 11.59%(19/164). GG, GA and AA genotypes were detected in VKORC1 polymorphism, among which the AA genotype accounted for 82.32%(135/164)and the GG genotype accounted for only 1.83%(3/164). The steady state dose for Warfarin in patients with the wild-type CYP2 C9*1/*1 was higher than in those with the heterozygote CYP2 C9*1/*3 and *1/*2(3.18±0.86 mg/d vs.2.27±0.51 mg/d, t=5.637, P<0.05). Patients with a mutant homozygotic AA genotype of VKORC1 required lower maintenance doses than those with the heterozygotic GA and GG genotypes(2.96±0.66 mg/d vs. 3.59±1.43 mg/d, t=-2.092, P<0.05). The steady-state dose for Warfarin in subjects carrying CYP2 C9 (*1/*2 or *3)and VKORC1 (GA and GG)was(2.00±0.63)mg/d, lower than in those carrying other genotype combinations( P<0.05). We established a new Warfarin dosing algorithm for elderly subjects aged 75 years and over containing height, creatinine, amiodarone usage, CYP2 C9 and VKORC1 mutants, and the accuracy of the new model was 56.0%, which could explain 56.0% of individual variability, and the accuracy was higher than that of the IWPC algorithm(56.0% vs. 45.8%, P<0.05). Conclusions:Polymorphisms of CYP2 C9 and VKORC1 clearly affect the steady-state dose for Warfarin in the elderly Han-Chinese population aged 75 years and over.A combination of pharmacogenomics with clinical factors can better guide warfarin medication in Han-Chinese people aged 75 years and over.

Objectives:To investigate the relationships between CYP2C9 and VKORC1 polymorphism and the steady-state dose of warfarin in Chinese Han patients with nonvalvular atrial fibrillation.Methods:A total 544 Chinese Han patients with atrial fibrillation who received warfarin anticoagulant therapy in Department of Cardiology of Beijing Hospital, Tongren Hospital, Xuanwu Hospital, Anzhen Hospital and Tiantan Hospital were enrolled from January 2016 to may 2019. The genotype and allele frequency in exon 1, 2, 3, 7 of CYP2C9 gene and 1639 site of VKORC1 gene were analyzed; and the general information, warfarin steady-state dose and concomitant medication of patients were recorded.Results:There were four genotypes CYP2C9:CYP2C9*1*1 (93.57%, 509/544), CYP2C9*1 *2 (0.18%, 1/544), CYP2C9*1 *3 (5.88%, 32/544) and CYP2C9*1 *60 (0.37%, 2/544); while VKORC1 had three genotypes: AA (82.72%, 450/544), GA (15.99%, 87/544) and GG (1.29%, 7/544). After reaching the anticoagulation index (INR 2.0-3.0), the steady-state dose of warfarin was the highest in patients with CYP2C9 *1/*1 and VKORC1 GA/GG genotypes, reaching (3.70±1.34) mg/d. The lowest steady-state dose of warfarin was (2.17±0.29)mg/d in patients with both new mutations ( F=22.09, P<0.001). Multiple linear regression analysis showed that body surface area, use of amiodarone, CYP2C9 and VKORC1 genotypes were the independent influencing factors of warfarin steady-state dose ( t=4.44, -2.90, -6.96, 2.14; P<0.05) and the steady-state dose prediction model of warfarin was established. Conclusion:Body weight, height, body surface area, gender, smoking, and combination of amiodarone may significantly affect the steady-state dose of warfarin in patients. CYP2C9 and VKORC1 mutant genotypes were significantly related to the steady-state dose of warfarin. The prediction model based on genetic factors and other influencing factors may effectively predict the steady-state dose of warfarin in Han patients with atrial fibrillation.

Objective To investigate the expressions of regulatory B cells and related cytokines in patients with Guillain-Barre syndrome (GBS).MethodsForty-four patients with GBS admitted to our hospital from October 2018 to June 2019 were enrolled as GBS group; 44 healthy subjects accepted physical examination in our hospital at the same period were selected as control group. Flow cytometry was used to determine the proportions of CD19+CD24hiCD38hi regulatory B cells and CD19+CD24hiCD27+ regulatory B cells in CD19+ lymphocytes in peripheral blood mononuclear cells of the two groups. ELISA was employed to detect the serum contents of interleukin (IL)-10, IL-35 and transforming growth factor (TGF)-β1 of the two groups.ResultsAs compared with those in the control group, the proportions of CD19+CD24hiCD38hi regulatory B cells and CD19+CD24hiCD27+ regulatory B cells in CD19+B lymphocytes of the GBS group were significantly decreased (P<0.05). As compared with the control group, the GBS group had significantly decreased IL-10 and IL-35 levels (P<0.05), and obviously increased TGF-β1 content without statistical difference (P>0.05).ConclusionRegulatory B cells play a role in the pathogenesis of GBS through IL-10 and IL-35 cytokine pathways.

Objective: To investigate the safety and efficacy of rotational atherectomy in the interventional treatment of coronary chronic total occlusion lesions. Methods: In this retrospective study,a total of 31 consecutive patients with coronary chronic total occlusion(CTO) lesions underwent rotational atherectomy in our hospital from February 2004 to December 2016 were enrolled,and the clinical features were analyzed. Coronary atherectomy was performed if balloon failed to cross the CTO lesions or balloon could not be fully dilated in the CTO lesions after wire crossing. The definition of procedure success was defined as residual stenosis less than 20% after implantation of drug eluting stent and rotational atherectomy. After the procedure, the patients were followed up to observe major adverse cardiac and cerebral vascular events which including cardiogenic death, myocardial infarction, cerebrovascular accident, and target lesion revascularization. Results: The 1.25 mm diameter burr was firstly selected in 80.6% (25/31) patients,and 96.8%(30/31) patients used only 1 burr to complete the rotational atherectomy procedure. The complication rate was 9.8% (3/31) including 1 patient with coronary dissection and 3 patients with slow flow or no flow. There was 1 patent with both coronary dissection and slow flow. The procedure success rate was 96.8%(30/31). Interventional treatment related myocardial infarction occurred in 3 patients during hospitalization.The 30 patients with procedure success were followed up 36(11, 96) months. The incidence rate of major adverse cardiac and cerebral vascular events was 13.3% (4/30), of which the cardiogenic death rate was 3.3% (1/30), the myocardial infarction rate was 6.7% (2/30), cerebrovascular accident rate was 3.3%(1/30),and the target lesion revascularization rate was 6.7% (2/30). Conclusion Rotational atherectomy is safe and effective in the interventional treatment of coronary CTO lesions.

The aim of this study was to investigate the pattern of distribution of mating type (MAT) genes of Tuber indicum in ectomycorhizosphere soils from natural T. indicum-producing areas and cultivated truffle orchards and ascocarp samples from different regions. Quantitative real-time PCR and multiplex PCR were used to weight the copy numbers of MAT1-1-1 and MAT1-2-1 in natural truffle soils and cultivated orchard soils. The effect of limestone on the pattern of truffle MAT genes and the correlation between soil properties and the proportion of MAT genes were also assessed. These results indicated that an uneven and nonrandom distribution of MAT genes was common in truffle-producing areas, cultivated truffle orchards, and ascocarps gleba. The competition between the two mating type genes and the expansion of unbalanced distribution was found to be closely related to truffle fructification. Limestone treatments failed to alter the proportion of the two mating type genes in the soil. The content of available phosphorus in soil was significantly correlated with the value of MAT1-1-1/MAT1-2-1 in cultivated and natural ectomycorhizosphere soils. The application of real-time quantitative PCR can provide reference for monitoring the dynamic changes of mating type genes in soil. This study investigates the distributional pattern of T. indicum MAT genes in the ectomycorhizosphere soil and ascocarp gleba from different regions, which may provide a foundation for the cultivation of T. indicum.
Calcium Carbonate ; Multiplex Polymerase Chain Reaction ; Phosphorus ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Soil