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Pulsed dye laser (PDL) is the main treatment for port wine stain (PWS), but a considerable number of patients show low clearances. The reason for the poor efficacy is related to PDL-induced angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in PDL-induced angiogenesis and can activate the tyrosine kinase activity of VEGF receptor (VEGFR) in endothelial cells. It triggers a full range of responses, and then participates in the regulation of angiogenesis. Tivozanib is an inhibitor of VEGFR tyrosine kinase activity, which can block the pro-angiogenic effect of VEGF and reduce vascular permeability.Different energy densities of PDL were used to irradiate the abdominal skin of rats. According to the general and pathological changes of the irradiated area, the energy density of 8 J/cmThe number of blood vessels in the 0.5% Tivozanib group and 1% Tivozanib group was significantly reduced on the 7, 10, and 14 days compared with the control group. The number of blood vessels in the 1% Tivozanib group was significantly reduced compared with the 0.5% Tivozanib group, indicating that Tivozanib successfully inhibited PDL-induced angiogenesis, and the inhibitory effect of 1% Tivozanib was more significant than that of 0.5% Tivozanib. Transcriptome sequencing results showed a total of 588 significantly differentially expressed genes, including 90 upregulated genes and 498 downregulated genes. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the significantly differentially expressed genes were mainly enriched in the metabolic pathways which were closely related to angiogenesis. Finally, real-time PCR was used to verify the genes with higher expression differences, the top ranking and closely related to angiogenesis, namely, Cxcl1, Cxcl2, Cxcl3, Cxcl6, Ccl3, Csf3, IL1β, iNOS, Mmp9, Mmp13, Plau, Ets1, Spp1, Nr4a1. The results were consistent with the trend of transcriptome sequencing results, which proved the reliability of this study.This study explored the inhibitory effect of Tivozanib on PDL-induced angiogenesis, and provided a new idea for the treatment of clinical PWS. Transcriptome sequencing explored the mechanism and provided reliable clues for later in-depth research.

Tailored management of cancer-related fatigue (CRF) is important for effective coping; however, it has been hindered by the lack of a comprehensive tool that assesses both symptoms and treatable influencing factors.The aim was to develop a cancer-related fatigue comprehensive assessment scale (CRF-CAS) and assess its psychometric properties.This was a mixed-method study.The study included two phases which were conducted in Zhejiang Province, China. In phase one, a literature search, brainstorming sessions, Delphi studies, cognitive interviews and a pilot study were conducted to construct and revise CRF-CAS indicators. In phase two, a questionnaire-based survey was conducted among cancer survivors. Item analysis was used to select and optimize indicators. Cronbach's α was calculated for reliability analysis. Validity analysis included concurrent validity and structural validity.A 93-item tool was initially constructed. Phase one ended with revision and optimization. The preliminary scale included five dimensions (CRF symptoms, physical activity, cognitive-emotional status, sleep status, nutritional status) and 30 items. The mean item-content validity index (I-CVI) and scale-level CVI universal agreement (S-CVI/UA) were .98, and the adjusted mean values of Kappa for indicators ranged from .91-1, as evaluated by the expert group. The Pearson correlation coefficient between the CRF-CAS and criterion scales ranged from .337-.862. Cronbach's α coefficient ranged from .624-.728. Respondents agreed that the scale was acceptable for administration and that it contributed to decision-making in fatigue management. Confirmatory factor analysis (CFA) indicated that the CRF-CAS fit well.The construction process of the CRF-CAS, involving panel discussion and expert and participant evaluations, was shown to be scientific and feasible. The CRF-CAS had relatively good validity and reliability in version 5 of its preliminary scale, which requires further improvement in future studies.

Hemodialysis (HD) is the most important treatment for patients with end-stage renal disease (ESRD). Thrombocytopenia is a potential treatment complication related to dialysis. Under normal circumstances, the platelet count would slightly decrease within the first hour of HD, but get restored towards the end of procedure. In most patients, the platelet count can be maintained within the normal range, and the occurrence of thrombocytopenia is relatively rare in clinical practice. Therefore, the possibility of thrombocytopenia in HD patients is often ignored. Moreover, thrombocytopenia might be misdiagnosed and mistreated. At present, almost all articles on the subject, apart from some case reports, focus on pseudothrombocytopenia and heparin-induced thrombocytopenia. In this review, we summarized various underlying causes, mechanisms, and diagnostic approaches to thrombocytopenia in HD patients. The review aims to provide a guide for clinicians interested in the causes and adequate treatment of thrombocytopenia.

Breast cancer is prone to form bone metastases and subsequent skeletal‐related events (SREs) dramatically decrease patients’ quality of life and survival. Prediction and early management of bone lesions are valuable; however, proper prognostic models are inadequate. In the current study, we reviewed a total of 572 breast cancer patients in three microarray data sets including 191 bone metastases and 381 metastases‐free. Gene set enrichment analysis (GSEA) indicated less aggressive and low‐grade features of patients with bone metastases compared with metastases‐free ones, while luminal subtypes are more prone to form bone metastases. Five bone metastases‐related genes (KRT23, REEP1, SPIB, ALDH3B2, and GLDC) were identified and subjected to construct a gene expression signature‐based nomogram (GESBN) model. The model performed well in both training and testing sets for evaluation of breast cancer bone metastases (BCBM). Clinically, the model may help in prediction of early bone metastases, prevention and management of SREs, and even help to prolong survivals for patients with BCBM. The five‐gene GESBN model showed some implications as molecular diagnostic markers and therapeutic targets. Furthermore, our study also provided a way for analysis of tumor organ‐specific metastases. To the best of our knowledge, this is the first published model focused on tumor organ‐specific metastases.

Aim Diabetic cardiomyopathy is an independent cardiac injury that can develop in diabetic individuals. Our previous study showed that C66, a curcumin analogue, protects against diabetes‐induced cardiac damage. The present study sought to reveal the underlying mechanisms of C66‐mediated cardioprotection. Methods An experimental diabetic model was established using JNK2−/− and wild‐type (WT) mice. C66 (5 mg/kg) was administered orally every other day for 3 months. Body weight, plasma glucose levels, cardiac function, and structure were measured. Masson trichrome and TUNEL staining were used to assess myocardial fibrosis and apoptosis, respectively. mRNA and protein levels of inflammation, fibrosis, oxidative stress, and apoptosis molecules were measured by quantitative PCR and Western blot, respectively. Results Neither C66 treatment nor JNK2 knockout affected body weight or plasma glucose levels. Cardiac inflammation, fibrosis, oxidative stress, and apoptosis were increased in WT diabetic compared to WT control mice, all of which were attenuated by C66 treatment. However, these pathological and molecular changes induced by diabetes were eliminated in JNK2−/− diabetic mice compared to JNK2−/− control mice, and C66 treatment did not further affect these parameters in JNK2−/− diabetic mice. Conclusions Our results indicate that C66 ameliorates diabetic cardiomyopathy by inhibiting JNK2 relative pathways.

Physalins are the major steroidal constituent of Physalis plants and display a range of biological activities. For this study, a rapid and sensitive high-performance liquid chromatography with triple quadrupole mass spectrometry method was developed for the simultaneous quantification of six physalins. Specifically, it was for the quantification of physalin A, physalin B, physalin D, physalin G, 4,7-didehydroneophysalin B, and isophysalin B in rat plasma and rat intestinal bacteria. After a solid-phase extraction, analytes and internal standards (prednisolone) were separated on a Shield reverse-phase C18 column (measuring 3 mm × 150 mm with an internal diameter of 3.5 μm) and determined using multiple reactions in a monitoring mode with a positive-ion electrospray ionization source. The mobile phase was a mixture of 0.1% formic acid in water (A) and acetonitrile (B) and was used at a flow rate of 0.6 mL/min. The intra- and interday precisions were within 15% with accuracies ranging from 86.2 to 114%. The method was validated and successfully applied to pharmacokinetics and stability studies of six physalins in rat plasma and rat intestinal bacteria, respectively. The results showed that physalin B and isophysalin B could not be absorbed by rats, and rat intestinal bacteria could quickly transform physalins.

Background The emergence of COVID‐19 pandemic resulted in an urgent need for the development of therapeutic interventions. Of which, neutralizing antibodies play a crucial role in the prevention and resolution of viral infection. Methods We generated antibody libraries from 18 different COVID‐19 recovered patients and screened neutralizing antibodies to SARS‐CoV‐2 and its mutants. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Clones were then reconstituted into whole human IgG for epitope binning assay and all 19 IgG were classified into 6 different epitope groups or Bins. Results Although all antibodies were found to bind RBD, the antibodies in Bin2 had superior inhibitory ability of the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 showed stronger binding affinity or ability to mutant RBDs (N501Y, W463R, R408I, N354D, V367F, and N354D/D364Y) derived from different SARS‐CoV‐2 strains as well, suggesting the great potential of these antibodies in preventing infection of SARS‐CoV‐2 and its mutations. Furthermore, such neutralizing antibodies strongly restricted the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized wildtype and more transmissible mutant pseudovirus entry into hACE2 overexpressed 293T cells. In Vero‐E6 cells, one of these antibodies can even block the entry of live SARS‐CoV‐2 into cells at 12.5 nM. Conclusions These results indicate that the neutralizing human antibodies from the patient‐derived antibody libraries have the potential to fight SARS‐CoV‐2 and its mutants in this global pandemic., The antibody libraries were generated from different COVID‐19 recovered patients for panning neutralizing antibodies to SARS‐CoV‐2 and its mutants. Then the positive clones were sequenced and reconstituted into whole human IgG for epitope binning assay. Finally, the antibodies were demonstrated to have great potential in blocking the infection of SARS‐CoV‐2 and its mutants.

The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron-oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI-SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI-SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g(-1) . They feature specific pH-sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose-dependent. In vitro transdermal studies demonstrate that the EPI-SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic-field-assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION-based vector for feasible transdermal therapy of skin cancer.

Aims and objectives: To examine Chinese cancer patients' fatigue self-management, including the types of self-management behaviours used, their confidence in using these behaviours, the degree of relief obtained and the factors associated with patients' use of fatigue self-management behaviours. Background: Fatigue places significant burden on patients with cancer undergoing chemotherapy. While some studies have explored fatigue self-management in Western settings, very few studies have explored self-management behaviours in China. Design: Cross-sectional self- and/or interviewer-administered survey. Methods: A total of 271 participants with self-reported fatigue in the past week were recruited from a specialist cancer hospital in south-east China. Participants completed measures assessing the use of fatigue self-management behaviours, corresponding self-efficacy, perceived relief levels plus items assessing demographic characteristics, fatigue experiences, distress and social support. Results: A mean of 4·94 (±2·07; range 1-10) fatigue self-management behaviours was reported. Most behaviours were rated as providing moderate relief and were implemented with moderate self-efficacy. Regression analyses identified that having more support from one's neighbourhood and better functional status predicted the use of a greater number of self-management behaviours. Separate regression analyses identified that greater neighbourhood support predicted greater relief from 'activity enhancement behaviours' and that better functional status predicted greater relief from 'rest and sleep behaviours'. Higher self-efficacy scores predicted greater relief from corresponding behaviours. Conclusions: A range of fatigue self-management behaviours were initiated by Chinese patients with cancer. Individual, condition and environmental factors were found to influence engagement in and relief from fatigue self-management behaviours. Relevance to clinical practice: Findings highlight the need for nurses to explore patients' use of fatigue self-management behaviours and the effectiveness of these behaviours in reducing fatigue. Interventions that improve patients' self-efficacy and neighbourhood supports have the potential to improve outcomes from fatigue self-management behaviours.

Malignant granular cell tumor is relatively uncommon, constituting only 1-2% of all granular cell tumors. It is a rare and unusual tumor, especially in non-typical sites, such as the uterine cervix, and grows more rapidly than benign granular cell tumor. It can be treated with surgical excision, but recurrence is possible and prognosis can be poor. A malignant granular cell tumor in the uterine cervix of a 37-year-old woman was incidentally diagnosed. The patient has a history of irregular vaginal bleeding. Uterine cervical biopsy under colposcope revealed a malignant granular cell tumor. After isophosphamide, etoposide, and cisplatin neoadjuvant chemotherapy, surgery was performed on the lesion, which approximately involved half the depth of cervical stroma. Computed tomography examination showed no local recurrence or distant metastasis during the 26-month follow-up period.

To evaluate clinical efficacy, toxicity, and survival outcomes of neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) among patients with cervical cancer stage IB2-IIB.In a retrospective clinical study at West China Second Hospital, Chengdu, data were analyzed from 414 patients who underwent NACT followed by radical surgery (NACT-RS) or RS alone between January 2008 and November 2009.The clinical response for NACT was 90%. Lymph node metastasis (25% versus 48%, P0.05) and deep cervical stromal invasion more than 0.5, (68% versus 91%, P0.05) were significantly lower among responders than among non-responders, respectively, in the NACT-RS group. The 2-year progression-free survival and 2-year overall survival were 93.0% and 95.5% in the NACT-RS group, and 94.5% and 97.1% in the RS group (P0.05). Parametric infiltration (hazard ratio [HR], 7.668; P0.05) and lymph node metastasis (HR, 7.714; P0.05) were independent risk factors for all study patients.Compared with RS, NACT-RS did not show a significant advantage for patients with locally advanced cervical cancer. However, the data provide the rationale for assessing NACT-RS in a multicenter randomized clinical trial setting. NACT may be considered as an alternative treatment when radiotherapy is not available.

Primary vaginal carcinoma is a rare gynecologic cancer. Radiotherapy is the standard treatment for patients affected by International Federation of Gynecology and Obstetrics stage II vaginal cancer. Neoadjuvant chemotherapy followed by radical surgery has been shown to be a valid therapeutic strategy in patients with cervical cancer; however, there is little information concerning the feasibility of neoadjuvant chemotherapy followed by radical surgery in patients with invasive vaginal carcinoma. We report the first case of stage II vaginal carcinoma with neoadjuvant chemotherapy followed by radical surgery combined with vaginal reconstruction using bilateral pudendal thigh fasciocutaneous flaps. The patient was free of disease with a satisfactory sexual life after 30 months.

Cis-dioxo-metal complex (NH3CH2CH2NH2)2.5 [Mo(V)0.5W(VI)0.5 O2-(OC6H4O)2] 1 was obtained by the reaction of tetra-butyl ammonium hexamolybdotungstate with 1, 2-dihydroxybenzene in the mixed solvent of CH3OH, CH3CN and ethylenediamine, and characterized by X-ray diffraction, UV-vis and EPR analysis. Compared with its analogous complexes (NH3CH2CH2-NH2)3[Mo(V)O2(OC6H4O)2] 2 and (NH3CH2CH2NH2)2 [W(VI)-O2(OC6H4O)2] 3, the results show that tungsten(VI) is less active in redox than molybdenum (VI) and that the change of the valence induced by substitution of W(VI) for Mo(V) in [MO2-(OC6H4O2]n- does not influence the coordination geometry of the complex anion in which the metal center exhibits distorted octahedral coordination with cis-dioxo catechol. The responses to EPR of complexes 1 and 2 are active but complex 3 is silent, and the UV-vis spectra exhibited by the three complexes are obvious different because of the different electronic configuration between the central Mo(V) and W(VI) ions in the complexes. It is noteworthy that complexes 1 and 2 have the similar EPR signal to flavoenzyme, suggesting that the three complexes have the same coordination geometry feature with the co-factor of flavoenzyme.

Four new sesquiterpenes including the novel sesquiterpene lactone (6R)-dehydroxysipanolinolide (1), two new eudesmane-type sesquiterpenes, curcolide (2) and curcodione (3), and a new xanthane-type sesquiterpene, curcumadionol (4), were isolated from Curcuma wenyujin Y. H. Chen et C. Ling, together with five known ones, 5-9. The structures of the new compounds were elucidated by spectroscopic methods. The inhibitory effects of compounds 1-9 on nitric-oxide production in lipopolysaccaride-activated macrophages were evaluated.

Introduction and objectives: Cervical cancer is the only gynaecological cancer that is staged clinically. The clinical stage of cervical cancer relies largely on the pelvic examination. The aim of this study is to analyse the discrepancy between clinical stage and pathological results, and to explore the accuracy of pelvic examination. Methods: We collected retrospective data from 818 patients with cervical carcinoma staged IB–IIB, who were treated with primary surgery from January 1999 to June 2007. Clinical stages of those patients were determined by pelvic examination without anaesthesia. After surgery, all the patients were assigned to pT category according to the pathological findings. Comparisons were made between these two stages. Results: The total concordance between clinical stage and pT category for stage IB–IIB was 53.1%, with an overestimation of 37.3% and an underestimation of 9.7%. The concordance in stage IB1, stage IB2, stage IIA and stage IIB were 85.4%, 77.4%, 35.3% and 20.5%, respectively. The most significant discrepancy was caused by the failure to detect the parametrial invasion accurately in stage IIB. The accuracy of pelvic examination to determine vaginal and parametrial disease was 70.2% and 74.0%, respectively. Conclusions: There are significant discrepancies between clinical stage and pathological results. Pelvic examination has its limitations in staging determination. Thus for operable cervical cancer, clinical stage alone is not reliable for selecting postoperative therapies and surgical staging system may be considered.

A new synthesis of di- and trisubstituted pyrroles is achieved by treating vinylogous diazoesters and readily available nitriles with a catalytic amount of silver(I) antimony hexafluoride.

Among dehydroxysipanolinolide (I), curcolide (II), curcodione (III) and curcumadionol (IV) only (III) reveals a very weak activity.

Two new germacrane-type sesquiterpene lactones, curdionolides A and B (1 and 2, resp.), and a novel germacrane-type sesquiterpene lactam, curdionolide C (3), were isolated from Curcuma wenyujin. Y. H. Chen et C. Ling together with five known germacrane-type sesquiterpenes, 4–8. The structures of the new compounds were elucidated by spectroscopic methods. The inhibitory effects of compounds 1–8 on nitric oxide (NO) production in lipopolysaccharide-activated macrophages were evaluated.

A novel chiral Rh(II) catalyst (1) is introduced for the [2 + 1]-cycloaddition of ethyl diazoacetate to terminal acetylenes and olefins with high enantioselectivity. The catalyst 1 consists of one acetate bridging group and three mono-N-triflyldiphenylimidazoline-2-one bidentate ligands (DPTI) spanning the Rh(II)-Rh(II) metallic center in a structure that was determined by single-crystal X-ray diffraction analysis. A rational mechanism is advanced that provides a straightforward explanation for the enantioselectivity and absolute stereochemical course of the [2 + 1]-cycloaddition reactions. A key element in this explanation is the cleavage of one of the Rh-O bonds of the bridging acetate group in the intermediate Rh-carbene complex to form a new pentacoordinate Rh carbene complex (formally 1.5 valent Rh) that can undergo [2 + 2]-cycloaddition with the C-C pi-bond of the acetylenic or olefinic substrate. Reductive elimination of the resulting adduct affords the cyclopropene or cyclopropane product. The C2-symmetry of the two DPTI ligands orthogonal to the bridging acetate also contributes to the high observed enantioselectivity and mechanistic clarity. The catalyst 1, which functions effectively at 0.5 mol %, can be recovered efficiently for reuse. Its ready availability, robustness, and effectiveness suggest it as a useful addition to the list of practical chiral Rh(II) catalysts for synthesis.