Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective This study aims to develop and validate a dynamic web-based nomogram for predicting kinetophobia in patients following percutaneous coronary intervention(PCI).Methods A prospective design was employed to selectively enroll 330 PCI patients admitted to a hospital in Hangzhou from December 2022 to July 2023.Single-factor analysis and Lasso regression were utilized to identify independent risk factors for kinesophobia post-PCI.Logistic regression was performed using R software,and a nomogram was constructed.The model was assessed through the area under the receiver operating characteristic curve(AUC)and Hosmer-Lemeshow tests.Results There were 206 cases of kinesiophobia in 330 patients after PCI,and the incidence was 62.4％.Logistic regression analysis identified combined heart failure,emergency surgery,NYHA cardiac function grade,ADL level,sedentary behavior,Chinese version of PROMIS Physical Function Summary Table score,and Chinese version of Perceptive Social Support Scale score as independent influencing factors for kinesophobia after PCI(P＜0.05).The AUC value of the model was 0.821,with a sensitivity of 70.4％and specificity of 82.0％.The Hosmer-Lemeshow fit test yielded a non-significant result(x2=9.350,P=0.314).Calibration and decision curves demonstrated the model's favorable calibration and clinical practicability.The C-index of the nomogram prediction model was 0.778,0.774,and 0.800,respectively,by 5-fold cross-validation,10-fold cross-validation,and the Bootstrap method.Conclusion The dynamic nomogram model developed in this study effectively predicts kinesophobia in patients after PCI.It provides valuable references and support for clinical staff in early identification of high-risk patients,enabling the formulation of individualized health education strategies and exercise rehabilitation plans.

Objective To compare the impact of immobilization base plates composed of 7 types of materials on the MR-simulation imaging quality used for radiotherapy,aiming to provide reference data for clinical applications.Methods Using identical T1 and T2 sequences of Siemens MR-simulator,the MR images of ACR Large Phantom were acquired on the Orfit carbon fiber laminate,polycarbonate (PC),high precision base plate (HP),Jinan Huayuxin BR,WR,KP and SP materials,respectively.The imaging quality without any plate was used as the baseline data.The following metrics were compared:1.High-contrast spatial resolution:the sharpness of 3 pairs of hole arrays was observed,which represented resolutions of 1.1 mm,1.0 mm and 0.9 mm on the LR and AP directions;2.Image intensity uniformity in terms of percent integral uniformity (PIU):PIU =100× [1-((high-low)/(high +low)];3.Low-contrast resolution:distinguishable spokes representing resolutions of 5.1％,3.6％,2.5％ and 1.4％ were recorded.According to ACR recommendations,high-contrast resolution of 1.0 mm,PIU of T1WI and T2＞82％and low-contrast spoke difference＜3 were considered as clinically acceptable.Results High-contrast T1WI and T2WI resolutions of no plate,PC plate,HP plate and KP material were all 0.9 mm,and those of the remaining materials were =worse than 0.9 mm.The T1WI and T2WI PIU of no plate was＞87％,and the PIU of carbon fiber plate was reduced by＞ 25％.The PIU decrease of remaining materials was within ±4％.Except the carbon fiber plate,the low-contrast spokes of the remaining materials were within ±3 compared with the reference.Conclusions In clinical settings,carbon fiber plate exerts the most significant effect upon the MR-simulation imaging quality,which is unsuitable for MR simulation.Imaging quality of PC and HP plates are consistent with that of no plate.BR and KP materials exert slight effect upon MR signal.The remaining materials are of potential values for the manufacture of immobilization devices and accessories.

Objective To analyze the efficacy of entecavir (ETV) combined with Peg IFNα-2b in chronic hepatitis B ( CHB) patients with low levels HBsAg following initial ETV treatment.Methods Sixty-nine CHB outpatients achieving serum HBsAg ＜2 000 IU/mL and HBV DNA＜100 IU/mL following initial ETV treatment in Pujiang People's Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to January 2016 were enrolled.Patients were randomly assigned in two groups: 39 patients in combination group received ETV (0.5 mg/d ) and Peg IFNα-2b (1.5 μg· kg－1· week －1, hypodermic injection), and 30 patients in ETV group received ETV (0.5 mg/d) alone.Serum HBsAg quantification, negative conversion rate of HBsAg and HBeAg , and levels of aminotransferase (ALT) were measured at baseline , 12th, 24th, 48th, 72th and 96th week after treatment.Results The levels of HBsAg in the combination group decreased gradually with the prolongation of therapy , which were lower than those in ETV group 24 week after treatment (Z＝－2.566,P＜0.05),and at 48th, 72th and 96th week (Z＝－3.499,－3.825 and －3.864,P＜0.01).Clearance of HBsAg appeared in the combination group at 24th week,the clearance rates were 7.70%(3/39) and 28.20%(11/39) at 24th and 96th week, respectively;while the clearance of HBsAg occurred in ETV group at 96th week, the clearance rate was only 3.30%(1/30).The negative conversion rates of HBsAg in combination group were higher than those in ETV group at 48th,72th and 96th week (P＜0.05 or＜0.01).In the combination group, there were 11 cases of clinical cure , 11 cases of clinical efficacy and 17 cases of clinical effectiveness , while there were 1, 1 and 28 cases in ETV group,respectively.The treatment effect of the combination group was better than that of ETV group(χ2＝18.496,P＜0.01).Serological conversion rates of HBeAg were 30.00%(6/20) and 65.00%(13/20) in combination group at 12th and 96th week, while those were 11.11%(2/18) and 22.22%(4/18) in ETV group at 48th and 96th week.There were significant differences in the HBeAg serological conversion rates at 12th, 24th, 72th and 96th week between two groups (P＜0.05 or ＜0.01). The levels of ALT in combination group increased at 12th and 24th week, which had significant difference compared with ETV group (Z＝－1.236 and －2.658,P＜0.05), and the ALT levels gradually declined 48 week after treatment in combination group and there were no statistical differences between two groups at other time points.The ETV combined with Peg IFNα-2b and low baseline HBeAg levels were associated with the clearance rate of HBsAg (both P＜0.01).Conclusions CHB patients with low HBsAg levels following initial ETV monotherapy can achieve high negative conversion rate of HBeAg and HBsAg with the combination treatment of ETV and Peg IFN α-2b.

Objective To observe the clinical effect of therapy of budesonide/formoterol powder for inhalation in treatment of adult with bronchial asthma.Methods 90 cases with bronchial asthma and were divided into observation group and control group randomly from February 2014 to February 2015.45 cases in each group.Control group was treated with budesonide inhalants +formoterol inhalants, observation group was given budesonide/formoterol powder inhalation.Changes of related indicators were followed up and recorded.Results After treatment, IL-5, IL-12 and IFN-γwere (60.2 ±9.7)pg/mL,(31.4 ±3.1)pg/mL,(1.6 ±0.2) ng/mL of observation group were better than control group (72.8 ±10.7)pg/mL,(38.5 ± 5.6)pg/mL,(2.3 ±0.3) ng/mL (P<0.05).After treatment,total effective rate in observation group was 68.9%, which was better than control group (48.9%)(P<0.05).Conclusion Clinical effect of budesonide/formoterol powder for inhalation in treatment of patients with bronchial asthma is accurate, and there is no obvious adverse reaction.

Objective To evaluate the clinical efficacy of Clostridium butyricum tablets in treatment of diarrhea in patients with hepatitis B-related liver cirrhosis.Methods Eighty-seven patients with hepatitis B-related liver cirrhosis and diarrhea were collected from Pujiang People' s Hospital in Zhejiang province during January 2011 and May 2013.According to random number table,patients were divided into Clostridium butyricum treated group (n =44) and control group (n =43).Both groups were given antiviral,liver support,jaundice-relieving and fluid infusion treatments,while patients in Clostridium butyricum group were given Clostridium butyricum tablets (2 tables per time,3 tables per day for 4 weeks) additionally.Diarrhea remission time,improvements in liver function and the complications were observed.Differences in measurement data were compared with t test,and enumeration data were compared with x2 test or rank-sum test.Results The total effective rate in Clostridium butyricum group was 95.45％ (42/44),while that in control group was 74.4％ (32/43) (Z =2.82,P ＜ 0.05).After 4 weeks of treatment,the improvements of alanine aminotransferase (ALT),aspartate transaminase (AST),total bilirubin (TBil),albumin (Alb) and Child-Pugh (CTP) score in Clostridium butyricum group were more marked than those in control group (t =2.13,2.57,4.83,5.93 and 3.30,P ＜ 0.01).Hepatic encephalopathy occurred in 2 patients in control group and none in Clostridium buayricum group.Conclusion Clostridium butyricum has significant curative effect on diarrhea in patients with hepatitis B-related liver cirrhosis,and it can also improve liver function and reduce the incidence of hepatic encephalopathy.

Bispecific antibodies have been exploited as both cancer immunodiagnostics and cancer therapeutics, which have shown promises in clinical trials in cancer imaging and therapy. To improve the anti-tumor effect, an scDb (bispecific single-chain diabody) was constructed from the variable domain genes of two scFvs (single-chain variable fragment antibodies) directed against human EGFR (epidermal growth factor receptor) and VEGFR2 (vascular endothelial growth factor receptor 2) extracellular domains. The anti-EGFR/ anti-KDR scDb was constructed into pHEN2 plasmid and expressed in Escherichia coli HB2151 host. After purification by one-step affinity chromatography of IMAC, scDb protein was characterized by Western blotting. The yield of scDb protein was 570 microg per liter medium. scDb bound to EGFR as efficiently as the parental antibody scFv-E10, while a little bit weaker than the parental antibody scFv-AK404R when bound to KDR. In conclusion, the scDb protein could bind both EGFR and KDR specifically and could be applied for further anti-tumor research.

Objective To study the perfusion imaging features of renal cell cancer(RCC) and their correlation with microvessel density(MVD) and vascular endothelial growth factor(VEGF) ex-pression status. Methods Dynamic contrast-enhanced multislice spiral CT was performed preopera-tively in 73 cases with histologically proven RCC (65 cases of clear cell carcinoma, 3 of papillary ade-nocarcinoma, and 5 of chromophobic carcinoma). Blood volume (BV), blood flow (BF), mean transit time (MTT), and permeability surface area product (PS) of tumors were recorded. MVD and VEGF expression status were studied by immunohistochemial staining. Results The mean BV, BF, MTT negative in 35 (47.9 %) cases, slightly positive in 24 (32.9 %) cases, moderate positive in 10 (13.7 %) cases, and intensively positive in 4 (5.5 %) cases. MVD of RCC was positively correlated with BV, BF and PS (P<0.01),and negatively correlated with MTT (P<0.05). No relationship was found be-tween the expression of VEGF and perfusion CT parameters. Conclusion Perfusion CT scan is use-ful to evaluate the angiogenesis status of RCC.