ALKBH5-mediated m6A modification of IL-11 drives macrophage-to-myofibroblast transition and pathological cardiac fibrosis in mice.

Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients.

Polyurethane foam dressing with non-adherent membrane improves negative pressure wound therapy in pigs.

OBJECTIVE: Negative pressure wound therapy (NPWT) is considered to be an effective technique to promote the healing of various wounds. The aim of this study was to evaluate different wound dressings combined with NPWT in treating wounds in Wuzhishan pigs. METHOD: Excisions were made in the backs of the pigs and were covered with polyvinyl alcohol (PVA) dressing, polyurethane (PU) dressing or PU dressing with non-adherent membrane (PU-non-ad). NPWT was applied to the wound site. In the control group, basic occlusive dressing (gauze) without NPWT was applied. On days 0, 3, 7, 14, 21 and 28 post-surgery, the wound size was measured during dressing change, and wound healing rate (WHR) was calculated. In addition, blood perfusion within 2cm of the surrounding wound was measured by laser doppler flowmetry. Dressing specimen was collected and microbiology was analysed. Granulation tissues from the central part of the wounds were analysed for histology, vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) mRNA expression. RESULTS: The PU-non-ad-NPWT significantly (p<0.01) accelerated wound healing in the pigs. Further pathological analysis revealed that the non-adherent membrane effectively protected granulation tissue formation in PU-NPWT treated wounds. The blood perfusion analysis suggested that the non-adherent membrane improved the blood supply to the wound area. Microbiological analysis showed that non-adherent membrane decreased the bacterial load in the PU-NPWT dressing. VEGF and CD31 mRNA expression was upregulated in the wound tissue from the PU-non-ad-NPWT treated groups. CONCLUSION: In this study, the PU dressing with non-adherent membrane was an ideal dressing in NPWT-assisted wound healing.

The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3.

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.

Comparative transcriptome analysis of sensory genes from the antenna and abdomen of Quadrastichus mendeli Kim.

Quadrastichus mendeli Kim is one of the most important parasitoids of Leptocybe invasa Fisher et La Salle, which is an invasive gall-making pest in eucalyptus plantations in the world. Gall-inducing insects live within plant tissues and induce tumor-like growths that provide the insects with food, shelter, and protection from natural enemies. Empirical evidences showed that sensory genes play a key role in the host location of parasitoids. So far, what kind of sensory genes regulate parasitoids to locate gall-inducing insects has not been uncovered. In this study, sensory genes in the antenna and abdomen of Q. mendeli were studied using high-throughput sequencing. In total, 181,543 contigs was obtained from the antenna and abdomen transcriptome of Q. mendeli. The major sensory genes (chemosensory proteins, CSPs; gustatory receptors, GRs; ionotropic receptors, IRs; odorant binding proteins, OBPs; odorant receptors, ORs; and sensory neuron membrane proteins, SNMPs) were identified, and phylogenetic analyses were performed with these genes from Q. mendeli and other model insect species. The gene co-expression network constructed by WGCNA method is robust and reliable. There were 10,314 differentially expressed genes (DEGs), and among them, 99 genes were DEGs. A comprehensive sequence resource with desirable quality was built by comparative transcriptome of the antenna and abdomen of Q. mendeli, enriching the genomic platform of Q. mendeli.

Development of a 3-MicroRNA Signature and Nomogram for Predicting the Survival of Patients with Uveal Melanoma Based on TCGA and GEO Databases.

Background: The aim of this study was to apply bioinformatic analysis to develop a robust miRNA signature and construct a nomogram model in uveal melanoma (UM) to improve prognosis prediction. Methods: miRNA and mRNA sequencing data for 80 UM patients were obtained from The Cancer Genome Atlas (TCGA) database. The patients were further randomly assigned to a training set (n = 40, used to identify key miRNAs) and a testing set (n = 40, used to internally verify the signature). Then, miRNAs data of GSE84976 and GSE68828 were downloaded from Gene Expression Omnibus (GEO) database for outside verification. Combining univariate analysis and LASSO methods for identifying a robust miRNA biomarker in training set and the signature was validated in testing set and outside dataset. A prognostic nomogram was constructed and combined with decision curve as well as reduction curve analyses to assess the application of clinical usefulness. Finally, we constructed a miRNA-mRNA regulator network in UM and conducted pathway enrichment analysis according to the mRNAs in the network. Results: In total, a 3-miRNA was identified and validated that can robustly predict UM patients' survival. According to univariate and multivariate cox analyses, age at diagnosis, tumor node metastasis (TNM) classification, stage, and the 3-miRNA signature significantly correlated with the survival outcomes. These characteristics were used to establish nomogram. The nomogram worked well for predicting 1 and 3 years of overall survival time. The decision curve of nomogram revealed a good clinical usefulness of our nomogram. What's more, a miRNA-mRNA network was constructed. Pathway enrichment showed that this network was largely involved in mRNA processing, the mRNA surveillance pathway, the spliceosome, and so on. Conclusions: We developed a 3-miRNA biomarker and constructed a prognostic nomogram, which may afford a quantitative tool for predicting the survival of UM. Our finding also provided some new potential targets for the treatment of UM.

Prophylactic Effect of Simultaneous Placement of Mesh on Incidence of Parastomal Hernia After Miles' Surgical Resection of Colorectal Cancer: A Prospective Study.

INTRODUCTION: To assess the prophylactic effect of simultaneous placement of mesh and the incidence of parastomal hernia (PSH) after abdominoperineal resection of rectal cancer. METHODS: This study included real-world data of 56 surgically resected patients with colorectal cancer who were consecutively assigned to two groups: control (no mesh, n = 32) and experimental (received mesh, n = 24). An artificial patch was placed under the tunica vaginalis of rectus abdominis for patients in the experimental group, whereas those in the control group received routine sigmoidostomy. The median follow-up time was >20 mo. The difference in hazards function was analyzed by cox regression analysis. The Kaplan-Meir analysis was used to determine the survival curves. A P value of <0.05 was considered as significant. RESULTS: The postoperative incidence rate of PSH was lower in the experimental (41.7%) group than in the control group (71.9%; P = 0.045). The PSH postoperative time in the experimental group was significantly delayed compared to the control group (48 mo versus 10 mo; P < 0.001). The risk of progression from H1 to H2 was less in the experimental group compared to the control group (49.28% versus 60.86%; P = 0.14). CONCLUSIONS: Prophylactic mesh placement significantly prolonged postoperative time for the recurrence of PSH. The incidence of recurrence of H2 (severe PSH) requiring secondary surgical repair was also reduced.

Nanoscale Modification of Titanium Implants Improves Behaviors of Bone Mesenchymal Stem Cells and Osteogenesis In Vivo.

The surficial micro/nanotopography and physiochemical properties of titanium implants are essential for osteogenesis. However, these surface characters' influence on stem cell behaviors and osteogenesis is still not fully understood. In this study, titanium implants with different surface roughness, nanostructure, and wettability were fabricated by further nanoscale modification of sandblasted and acid-etched titanium (SLA: sandblasted and acid-etched) by H2O2 treatment (hSLAs: H2O2 treated SLA). The rat bone mesenchymal stem cells (rBMSCs: rat bone mesenchymal stem cells) are cultured on SLA and hSLA surfaces, and the cell behaviors of attachment, spreading, proliferation, and osteogenic differentiation are further analyzed. Measurements of surface characteristics show hSLA surface is equipped with nanoscale pores on microcavities and appeared to be hydrophilic. In vitro cell studies demonstrated that the hSLA titanium significantly enhances cell response to attachment, spreading, and proliferation. The hSLAs with proper degree of H2O2 etching (h1SLA: treating SLA with H2O2 for 1 hour) harvest the best improvement of differentiation of rBMSCs. Finally, the osteogenesis in beagle dogs was tested, and the h1SLA implants perform much better bone formation than SLA implants. These results indicate that the nanoscale modification of SLA titanium surface endowing nanostructures, roughness, and wettability could significantly improve the behaviors of bone mesenchymal stem cells and osteogenesis on the scaffold surface. These nanoscale modified SLA titanium scaffolds, fabricated in our study with enhanced cell affinity and osteogenesis, had great potential for implant dentistry.

A Retrospective Study of SVF-gel Compared With Nanofat Combined With High-density Fat in the Treatment of Early Periorbital Aging.

PURPOSE: To compare the effectiveness of transplantation with stromal vascular fraction (SVF)-gel or nanofat combined with high-density fat prepared with the Coleman technique (nanofat+high-density fat) to restore volume in the periorbital region or for periorbital rejuvenation in early periorbital aging. METHODS: This retrospective study included 103 patients who received a transplant of SVF-gel (n = 58) or nanofat+high-density fat (n = 45) to restore volume in the periorbital region (n = 85) or for periorbital rejuvenation (n = 18) in our hospital between January 2016 and January 2020. Patient satisfaction and the reoperation rate were evaluated. RESULTS: All patients had improved periorbital contouring and augmentation. Among the patients that received treatment to restore volume in the periorbital region, 17% and 65.9% of patients administered SVF-gel were very satisfied or satisfied, and 5.3% and 44.7% of patients administered nanofat+high-density fat were very satisfied or satisfied. PATIENTS: administered SVF-gel were significantly more satisfied than patients administered nanofat+high-density fat with improvements in periorbital contouring ( p < 0.05). Among the patients that received treatment for periorbital rejuvenation, 54.5% and 27.3% of patients administered SVF-gel were very satisfied or satisfied, and 28.6% and 42.8% of patients administered nanofat+high-density fat were very satisfied or satisfied. There was no significant difference between groups ( p > 0.05). Some patients underwent a second operation after 3 to 8 months. Patients administered SVF-gel to restore volume in the periorbital region had a significantly lower reoperation rate than patients administered nanofat+high-density fat (12.7% [6/47] vs. 34.2% [13/38]; p < 0.05). There was no significant difference in the reoperation rate in patients treated for periorbital rejuvenation (9.1% [1/11] vs. 14.3% [1/7]; p > 0.05). CONCLUSION: SVF-gel and nanofat+high-density fat are effective for restoring volume in the periorbital region and for periorbital rejuvenation in early periorbital aging. The reoperation rate was significantly lower and patient satisfaction scores were significantly higher in patients administered SVF-gel to restore volume in the periorbital region compared with patients administered nanofat+high-density fat.

Association of Preoperative Coagulability With Incidence and Extent of Portal Vein Tumor Thrombus and Survival Outcomes in Hepatocellular Carcinoma After Hepatectomy: A Large-Scale, Multicenter Study.

BACKGROUND: Occurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR). METHODS: Patients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method. RESULTS: This study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (P<0.005). Of the 592 HCC subjects who had types I/II PVTT following R0 LR, there were 106 (17.9%), 342 (57.8%) and 144 (24.3%) patients in the High, Normal and Low INR groups, respectively. RFS and OS rates were markedly worse in patients in the Low INR group relative to those in the Normal and High INR groups (median RFS, 4.87 versus 10.77 versus 11.40 months, P<0.001; median OS, 6.30 versus 11.83 versus 12.67 months, P<0.001). CONCLUSION: Preoperative INR influenced the incidence and extent of PVTT in HCC. Particularly, patients with HCC and PVTT in the Low INR group had worse postoperative prognosis relative to the High and Normal INR groups.

ω-3 Polyunsaturated Fatty Acids Facilitate the Repair of Peripheral Nerve Defects with Chemically Extracted Acellular Allograft in Rats.

Acellular allograft (ACA) improves the repair and reconstruction of long peripheral nerve defects. ω-3 Polyunsaturated fatty acids (PUFAs) carry a neuroprotective potential, and their effects on ACA bridging were elucidated. Thirty rats with long gap sciatic nerve defects (15 mm long) were randomly divided into three groups (n = 10): ACA, ACA + PUFAs, and autograft (AU). Limb condition, wet weight of tibialis anterior muscle (TAM), nerve electrophysiology, S-100, horseradish peroxidase (HRP), and percentage of splenic CD4+ and CD8 + T-lymphocytes were evaluated for 12 weeks after the operation. Rats in the AU and ACA + PUFA groups showed superior condition in affected limbs compared to the ACA group. At 12 wk after surgery, the wet weight of TAM in the ACA + PUFA group was higher than that in the ACA group (0.4519 ± 0.1185 vs. 0.3049 ± 0.1272; P < 0.01) but lower than that in the AU group (0.4519 ± 0.1185, 0.5628 ± 0.0092; P < 0.05). In all the three groups, sole irritation elicited withdrawal reflex, and S-100 staining was detected in plantar skin. Moreover, horseradish peroxidase staining was overt in both the ventral horn and dorsal root ganglion of the spinal cord. Nerve conduction velocity (m/s), amplitude of action potential (mV), or somatosensory evoked potentials in ACA + PUFAs (28.81 ± 1.04, 2.20 ± 0.27, 6.98 ± 0.29) were significantly different from that in the AU (35.71 ± 1.28, 1.81 ± 0.19, 8.15 ± 0.52; P < 0.05) and ACA (20.03 ± 1.94, 2.95 ± 0.36, 5.22 ± 0.53; P < 0.01) groups. The percentages of splenic CD4+ and CD8+ cells were similar among the three groups. Omega-3 PUFAs improve the bridging effect of ACA on long gap peripheral nerve defects by promoting neuroprotection without arousing an immune response.

MiR-325-3p mediate the CXCL17/CXCR8 axis to regulate angiogenesis in hepatocellular carcinoma.

INTRODUCTION: MicroRNA-325-3p (miR-325-3p) is involved in the progression of a great number of tumors. However, the regulatory mechanism of miR-325-3p on hepatocellular carcinoma (HCC) remains unclear. AIM: In this paper, we aim to investigate the underlying mechanism by which miR-325-3p regulate the progression of HCC. METHODS: RT-qPCR was performed to detect the levels of miR-325-3p, CXCL17, and CXCR8. Western bolt was conducted to determine the levels of pro-angiogenic factors VEGF, FGF2, Ang-1 and PDGF-B. Immunohistochemistry was carried to detect the distribution and expression of Ki-67 and CD34 in HCC tissues. MTT and colony formation were carried to evaluate cell proliferation, endothelial tube-formation assay was used detect tubule formation, and transwell assay was performed to evaluate cell migration and invasion ability. Dual-luciferase activity assay was used to verify the relationship between miR-325-3p and CXCL17. RESULTS: MiR-325-3p was down-regulated in HCC cells and tissues, miR-325-3p overexpression inhibited the proliferation, migration and invasion of HCC cells. Besides, miR-325-3p overexpression inhibited angiogenesis of HCC. CXCL17 is a direct target of miR-325-3p and partially mediates the effect of miR-325-3p on proliferation, migration, invasion and angiogenesis of HCC. CONCLUSION: MiR-325-3p regulated angiogenesis of HCC via mediating CXCL17/CXCR8 axis, indicating miR-325-3p may serve as a promising therapy biomarker for HCC.

Actual long-term survival in HCC patients with portal vein tumor thrombus after liver resection: a nationwide study.

BACKGROUND: Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. METHODS: A nationwide database of HCC patients with PVTT who underwent liver resection with 'curative' intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS: The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 µmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (< 1 year), and recurrence treatments were independent prognostic factors associated with actual long-term survival. CONCLUSION: One in nine HCC patients with PVTT reached the long-term survival milestone of 3 years after resection. Major hepatectomy, controlling intraoperative blood loss, R0 resection, adjuvant TACE, and 'curative' treatment for initial recurrence should be considered for patients to achieve better long-term survival outcomes.

Threat appeals in public service announcements: Effects of message framing and relationship norms.

Threat appeals have been widely utilized in numerous types of public service announcements (PSAs), and previous research has focused on the impact of the inherent messages in these announcements. By examining the research on the effects of framing PSAs in terms of the threat of the message to oneself or others, we proposed a clear conceptualization of "threat-target framing." The first two studies addressed the direct effects of threat-target framing and found that other-oriented threat appeals can evoke more guilt than can self-oriented threat appeals. Moreover, self-oriented threat appeals can evoke more fear and immediately direct recipients' attention to the smoker than can other-oriented threat appeals. Study 3 reported that a contextual factor-relationship norms-was introduced as a potential moderating factor. Results showed that relationship norms had the potential to moderate the effect of threat-target framing on recipients' fear response, but not the effect on recipients' guilt and coping response. In sum, the results highlighted the importance of message framing of advertising copies and the placement context. Our findings may be useful in understanding the antecedents of the persuasiveness of PSAs.

Association between clinicopathologic characteristics and BRAFV600E expression in Chinese patients with Langerhans cell histiocytosis.

BACKGROUND: The identification of V-raf murine sarcoma viral oncogene homolog B1 (BRAF)V600E mutations has been recommended in patients with Langerhans cell histiocytosis (LCH) with difficult diagnosis and failure of first-line treatment. The reported frequencies of BRAFV600E mutations vary in Chinese patients with LCH. METHODS: We conducted a retrospective analysis of LCH patients with a definitive pathological diagnosis who were hospitalized between 2013 and 2017. The BRAFV600E mutations were detected with the human BRAFV600E amplification refractory mutation system-PCR (ARMS-PCR) kit from the collected tissue samples. RESULTS: This study consisted of 46 male (68.7%) and 21 female (31.3%) patients, with a mean age of 29.1 years (range, 2-76 years). Most were adults (45/67.2%) with the multisysytem-LCH (MS-LCH) disease subtype (49/61.3%). The overall frequency of BRAFV600E mutations was 22.4% (15 of 67 patients), confirmed by PCR analysis. These mutations were not closely correlated with age (nonadults vs. adults = 5/22.7% vs. 10/22.2%, P = 0.54), gender (female vs. male = 9/19.6% vs. 6/28.6%, P = 0.61), LCH classification type (single system: MS-risk organ+ : MS-risk organ- = 3/16.7%: 12:28.6%: 0, P = 0.19) or prognosis (cured: improved/stable: exacerbated: died = 4/44.4%: 19.2%: 20%: 0, P = 0.37). There were 33 patients (49.2%) with lung involvement, and 12 patients (36.3%) underwent lung biopsies; after screening, four patients were diagnosed with solitary pulmonary LCH, all of whom were negative for BRAFV600E mutations. CONCLUSION: The BRAFV600E mutation rate in patients with LCH was lower than those reported in other studies. In addition, BRAFV600E mutations might not be correlated with age, gender, LCH classification type or prognosis for Chinese cases.

Design, synthesis, and biological evaluation of novel 3-(thiophen-2-ylthio)pyridine derivatives as potential multitarget anticancer agents.

A series of novel 3-(thiophen-2-ylthio)pyridine derivatives as insulin-like growth factor 1 receptor (IGF-1R) inhibitors was designed and synthesized. IGF-1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU-DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR-1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50 ] values, HepG2: 2.98 ± 1.11 µM and WSU-DLCL2: 4.34 ± 0.84 µM) exhibited good inhibitory activities against fibroblast growth factor receptor-2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 µM. Additionally, the cell-cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing.

A case of mammary sparganosis due to infection with Spirometra mansoni.

The authors report the case of a 56-year-old woman with mammary sparganosis due to infection with a plerocercoid tapeworm larva of Spirometra mansoni. Magnetic resonance imaging revealed an area of heterogeneous density in outer upper quadrant of the right breast, with a high likelihood of malignancy. During surgery for the removal of a granuloma, the parasite was discovered and excised. The authors review the pathological and imaging features of mammary sparganosis.

Effects of Smoking Cessation with Nicotine Replacement Therapy on Vascular Endothelial Function, Arterial Stiffness, and Inflammation Response in Healthy Smokers.

The effects of nicotine replacement therapy (NRT)-aided smoking cessation on vascular function are not fully clarified. We investigated 100 healthy smokers who were motivated to quit and received NRT for a 3-month period. Vascular endothelial function (measured by reactive hyperemia-peripheral arterial tonometry [RH-PAT]), arterial stiffness (measured by augmentation index [AI] and brachial-ankle pulse wave velocity [baPWV]), and systemic inflammation markers (including serum soluble intercellular adhesion molecule-1 [sICAM-1] and interleukin-1ß [IL-1ß]) were assessed at baseline and 3 and 12 months of follow-up. After 3 months of intervention, endothelial function, arterial stiffness, and inflammatory markers significantly improved (RH-PAT increased, AI and baPWV decreased, sICAM-1 and IL-1ß decreased, all P < .05) for the participants who abstained from smoking completely, but for those who did not abstained completely, RH-PAT, AI, baPWV, and IL-1ß remained unchanged. At 12 months follow-up, endothelial function (RH-PAT), arterial stiffness (AI and baPWV), and inflammatory markers (sICAM-1 and IL-1ß) were further improved in participants who abstained from smoking (P < .001), while the above parameters deteriorated in continued smokers (P < .05). In conclusion, vascular dysfunction can be reversible after NRT-aided smoking cessation in healthy smokers and vascular function could be further damaged if they continue smoking.

Cushing's disease with pulmonary Cryptococcus neoformans infection in a single center in Beijing, China: A retrospective study and literature review.

BACKGROUND: Patients with Cushing's disease (CD) with hypercortisolism have an increased risk of opportunistic infection. However, most CD patients exposed to infections are diagnostic latency, leading to a poor prognosis. METHODS: Six patients in our hospital and an additional six patients in the literature were included in this study. Clinical information of CD patients with pulmonary Cryptococcus neoformans are reviewed. RESULTS: The average baseline total cortisol and ACTH in serum at 8 am of all the patients was 44.85 µg/dL (normal range 4.0-22.3 µg/dL) and 200.3 pg/mL (normal range 0-46 pg/mL), respectively. Lymphopenia was found in 2 out of 6 patients in our hospital. The pulmonary radiologic findings included nodules (4/12), masses with or without a cavity (5/12), infiltration (5/12), and consolidation (4/12). The diagnosis of C.neoformans was established by lung pathology results (7/12), microorganism culture (3/12), and serum cryptococcal polysaccharide antigen (4/12). Lung lobectomy was performed in two patients who had a nodule in one lung lobe. Antifungal drugs were administered, including amphotericin-B (7/12), fluconazole (4/12), flucytosine (2/12) and liposomal amphotericin (1/12). Additional therapies for CD included trans-sphenoidal pituitary adenoma surgery (9/12), adrenalectomy (1/12) and ketoconazole (2/12). Seven patients survived, and five patients died. CONCLUSION: Pulmonary C.neoformans is an uncommon but fatal opportunistic infection in CD patients. Pulmonary nodules or masses should be aggressively investigated to exclude the C.neoformans among CD patients. The infiltration lesions in chest CT scan and lymphopenia are associated with poor prognosis.

Effect of Huaier granule on recurrence after curative resection of HCC: a multicentre, randomised clinical trial.

OBJECTIVE: There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need. DESIGN AND RESULTS: A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively. CONCLUSIONS: This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group. TRIAL REGISTRATION: NCT01770431; Post-results.