AK-MADDPG-Based Antijamming Strategy Design Method for Frequency Agile Radar.

Frequency agility refers to the rapid variation of the carrier frequency of adjacent pulses, which is an effective radar active antijamming method against frequency spot jamming. Variation patterns of traditional pseudo-random frequency hopping methods are susceptible to analysis and decryption, rendering them ineffective against increasingly sophisticated jamming strategies. Although existing reinforcement learning-based methods can adaptively optimize frequency hopping strategies, they are limited in adapting to the diversity and dynamics of jamming strategies, resulting in poor performance in the face of complex unknown jamming strategies. This paper proposes an AK-MADDPG (Adaptive K-th order history-based Multi-Agent Deep Deterministic Policy Gradient) method for designing frequency hopping strategies in frequency agile radar. Signal pulses within a coherent processing interval are treated as agents, learning to optimize their hopping strategies in the case of unknown jamming strategies. Agents dynamically adjust their carrier frequencies to evade jamming and collaborate with others to enhance antijamming efficacy. This approach exploits cooperative relationships among the pulses, providing additional information for optimized frequency hopping strategies. In addition, an adaptive K-th order history method has been introduced into the algorithm to capture long-term dependencies in sequential data. Simulation results demonstrate the superior performance of the proposed method.

Analysis of factors impacting postoperative pain and quality of life in patients with mixed hemorrhoids: A retrospective study.

BACKGROUND: Hemorrhoids are among the most common and frequently encountered chronic anorectal diseases in anorectal surgery. They are venous clusters formed by congestion, expansion, and flexion of the venous plexus in the lower part of the rectum. Mixed hemorrhoids bleed easily and recurrently, and this can result in severe anemia. Hence, they may have a negative effect on the health of the patient and surgical treatment is required. Milligan-Morgan hemorrhoidectomy has been widely used since 1937 for the treatment of grade III and IV hemorrhoids. However, most patients experience different degrees of postoperative pain that may cause anxiety. AIM: To assess the factors influencing pain scores and quality of life (QoL) in patients with mixed hemorrhoids post-surgery. METHODS: The clinical data of patients with mixed hemorrhoids who underwent Milligan-Morgan hemorrhoidectomy were collected retrospectively. The basic characteristics of the enrolled patients with mixed hemorrhoids were recorded, and based on the Goligher clinical grading system, the hemorrhoids were classified as grades III or IV. The endpoint of this study was the disappearance of pain in all patients. Quantitative data were presented as mean ± SD, such as age, pain score, and QoL score. Student's t-test was used to compare the groups. RESULTS: A total of 164 patients were enrolled. The distribution of the visual analog scale pain scores of all patients at 3, 7, 14 and 28 d after surgery showed that post-surgery pain was significantly reduced with the passage of time. Fourteen days after the operation, the pain had completely disappeared in some patients. Twenty-eight days after the surgery, none of the patients experienced any pain. Comparing the World Health Organization Quality of Life - BREF self-reporting questionnaire scores of patients between 14 and 28 d after surgery, we observed that the quality-of-life scores of the patients post-surgery had significantly improved. There were six items that were compared at 14- and 28-d post-surgery. The mean QoL score 28 d after surgery (4.79 ± 0.46) was higher than that at 14 d post-surgery (3.79 ± 0.57). The mean health condition score 28 d after surgery (4.80 ± 0.41) was also higher than that at 14 d post-surgery (4.01 ± 0.62). The mean physical health score 28 d after surgery (32.10 ± 2.96) was significantly higher than that at 14 d post-surgery (23.41 ± 2.85). The mean psychological health score 28 d after surgery (27.22 ± 1.62) was significantly higher than that at 14 d post-surgery (21.37 ± 1.70). The mean social relations score 28 d after surgery (12.21 ± 1.59) was significantly higher than that at 14 d post-surgery (6.32 ± 1.66). The mean surrounding environment score 28 d after surgery (37.13 ± 2.88) was significantly higher than that at 14 d post-surgery (28.42 ± 2.86). The differences in quality-of-life scores at day 14 and day 28 post-surgery were observed to be statistically significant (P < 0.001). CONCLUSION: Milligan-Morgan hemorrhoidectomy can significantly improve the postoperative QoL of patients. Age, sex, and the number of surgical resections were important factors influencing Milligan-Morgan hemorrhoidectomy.

Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource.

Schistosoma japonicum causes schistosomiasis in humans and livestock in the Asia-Pacific region. Knowledge of the genome of this parasite should improve understanding of schistosome-host interactions, biomedical aspects of schistosomiasis and invertebrate evolution. We assigned 43,707 expressed sequence tags (ESTs) derived from adult S. japonicum and their eggs to 13,131 gene clusters. Of these, 35% shared no similarity with known genes and 75% had not been reported previously in schistosomes. Notably, S. japonicum encoded mammalian-like receptors for insulin, progesterone, cytokines and neuropeptides, suggesting that host hormones, or endogenous parasite homologs, could orchestrate schistosome development and maturation and that schistosomes modulate anti-parasite immune responses through inhibitors, molecular mimicry and other evasion strategies.

The association between Day-1 urine cadmium excretion and 30-day mortality in patients with acute myocardial infarction: A multi-institutional cohort study.

BACKGROUND: The aim of this study was to investigate the relationship between day-1 urine cadmium excretion and 30-day mortality in patients with acute myocardial infarction (AMI) at two centers. METHODS: A total of 286 patients (222 males and 64 females) with AMI from Huashan Hospital, Shanghai and Chang Gung Memorial Hospital, Taiwan were enrolled. Basic vital signs, history, laboratory results, and day-1 urine excretion of cadmium (D1UECd) were recorded. Disease severity was assessed during the first hospitalization using Killip score, APACHE II score, and SOFA score. The main endpoint was 30-day mortality. RESULTS: Among the 286 patients, 218 were from Chung Gung Memorial Hospital and 68 were from Huashan Hospital with an average age of 64.2 years. Forty (14%) patients died within 30 days after AMI. The average 24-h urine cadmium level among the Chung Gung Memorial Hospital cohort was 1.5 ± 2.4 µg compared to 1.7 ± 1.7 µg among Huashan Hospital cohort, both higher than the local populations. A higher D1UECd level was significantly associated with a greater risk of 30-day mortality (odds ratio 1.68, 95% confidence interval 1.30-2.16) after controlling for a number of covariates. The ability of D1UECd to discriminate 30-day mortality was excellent, with a very high area under the curve (87.2%, 95% CI 82.0-92.5%). CONCLUSION: D1UECd was positively correlated and an independent predictor of 30-day mortality in the enrolled AMI patients. D1UECd may be a simple, objective prognostic scoring system in AMI patients.

The exosome of platelet endothelial cell adhesion molecule-1 (PECAM1) protein: A potential risking star in high blood pressure patients (HBPP).

ABSTRACT: A number of studies have demonstrated that exosomes were involved in important physiological and pathological processes through cell-to-cell communication in cardiovascular disease, which contained nucleic acids, proteins, and lipid contents. In our study, we found that the protein platelet endothelial cell adhesion molecule-1 (PECAM1) was an extracellular vesicle in the blood of high blood pressure patients (HBPP).Isolated the vesicles from the blood of HBPP and health examiners and detected its size and morphology with nanoparticle tracking analysis, then we identified its surface protein CD63, CD81, and the protein expression of PECAM1 in the exosome with western blot. Furthermore, we analyzed the correlation between the expression of PECAM1 and the high blood degree with linear regression analysis.Our results showed that the morphology of extracellular vesicles was more evident in high blood pressure groups than healthy controls, and the protein expression of PECAM1 was also abundant in the vesicles of HBPP, however, there were no extracellular vesicles in the blood samples of healthy controls. Besides, linear regression showed the linear correlation coefficient R = 0.901, P < .01 between the expression of PECAM1 and the systolic blood pressure of the high blood patients. Therefore, the exosome of protein of PECAM1 was a potential risking star in HBPP.

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection.

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-gamma by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naïve T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4(+)CD25(high)Foxp3(+) regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

[Establishment of target genomic DNA capturing system for next generation sequencing].

The motivation of this research is to establish a system of target genomic DNA capture and enrichment, which could be used in deep sequencing of target regions with next-generation sequencing. To design the 120 bp capture probes (baits) and prepare the SureSelect reagents, 2,414,977 bp human genomic sequence of 11,824 exons in 1250 genes were submitted to the Agilent eArray platform and manufactured by Agilent. Two human genomic DNA samples were used and conducted the successive experiments for sequencing library construction: shearing fragmentation by sonication, blunt-ending and phosphorylation, adaptor ligation, 150-200 bp fragments size selection, followed by hybridization with the baits, hybrid selection with magnetic beads, and PCR amplification. Prior to SOLiD sequencing reaction, the libraries were amplified with emulsion PCR and enriched with the P2 enrichment beads. The library samples were loaded to sequencing Chip for Work Flow Analysis (WFA) or sequencing running with default parameters. The results displayed that 46 509 baits were designed and synthesized for 11,147 gene regions, and SureSelect capture probe regent was prepared. Real-time PCR showed the target enrichment efficiency up to 2(9) times with the SureSelect system. WFA revealed that the libraries were suitable for SOLiD Sequencing. The sequencing data revealed that 70% of the unique mapped sequence tags matched the target regions, and the average coverage of the target regions were above 200-fold. All these demonstrated the feasibility of the established system of target genome sequence capture for next generation DNA sequencing.

Loss of ACSM3 confers worsened prognosis and immune exclusion to cutaneous melanoma.

Aim: Malignant melanoma (MM) is a highly aggressive cutaneous cancer with undetermined underlying genetic disposition. We aim to evaluate prognostic and mechanistic role of ACSM3 in MM. Methods: In silico reproduction of TCGA MM dataset, GEO dataset, GDSC dataset and human protein atlas was performed to establish differential expression of ACSM3. In vitro and in vivo validation using A375 and SKMEL1 MM cells were performed to profile tumorigenic role and functional attribution of the gene. Results: ACSM3 expression was significantly downregulated in MM. Lower expression of ACSM3 conferred worsened prognosis of MM. Lower ACSM3 was observed in Asian ethnicity. Knock-down (KD) and overexpression (OE) of ACSM3 resulted in significant increased and decreased proliferation, invasion and colony formation in MM cells, respectively. Pathway annotation revealed significantly active immune response invoked by ACSM3. Lower ACSM3 expression was associated with decreased CD8+, macrophage and dendritic cell infiltration. Cox regression revealed loss of survival contribution of ACSM3 in the presence of immune infiltrates supporting immune regulatory role of ACSM3. Drug sensitivity analysis revealed BRAF inhibitor PLX-4720 was sensitive in both MM cells. ACSM3 expression showed no correlation with immune checkpoint molecules. Combined ACSM3-OE and PLX-4720 in MM cells showed synergistic inhibition in MM cells and xenograft murine models with no significant toxicity. Conclusion: Loss of ACSM3 was associated with poor prognosis in MM. Overexpression of ACSM3 synergistically inhibited MM with PLX-4720. ACSM3 was potentially associated with immune exclusion in MM. Further validation was warranted in future studies.

Treatment-related adverse events as surrogate to response rate to immune checkpoint blockade.

BACKGROUND: Immune checkpoint blockade (ICB) brings hope to many late-stage cancer patients yet its marker for response remains elusive. METHODS: We developed a hypothesis that treatment-related adverse events (TrAEs) could predict objective response rate (ORR) to ICB. We plotted ORR against corresponding any and grade 3 to 5 (G3-5) TrAEs across a variety of cancer types by performing a meta-analysis using linear regression. RESULTS: We identified 113 eligible studies encompassing 25 types of malignancies that were treated with ICB or ICB-based regimes. A significant linear correlation was observed for any and severe TrAEs, respectively. The correlation coefficient was 0.57 (r = 0.324) for any TrAE and 0.61 (r = 0.37) for G3-5 TrAE. For melanoma, the correlation coefficient was 0.81 (r = 0.57) for any TrAE and 0.65 (r = 0.42) for G3-5 TrAEs. For RCC, the correlation coefficient was 0.86 (r = 0.74) for any TrAE and 0.91 (r = 0.83) for G3-5 TrAE. For NSCLC, the correlation coefficient was 0.55 (r = 0.3) for any TrAE and 0.74 (r = 0.86) for G3-5 TrAE. For UC, the correlation coefficient was 0.47 (r = 0.68) for any TrAE and 0.27 (r = 0.52) for G3-5 TrAE, yet the correlation was insignificant for severe AEs. CONCLUSION: Our findings suggest that over half of ICB responses could be reflected by any adverse events and ∼60% of responses could be reflected by severe AEs. Further validation is needed in individual trials.

Comprehensive analysis of copy number variance and sensitivity to common targeted therapy in clear cell renal cell carcinoma: In silico analysis with in vitro validation.

BACKGROUND: Chromosomal rearrangements are common in clear cell renal cell carcinoma (ccRCC) and their roles in mediating sensitivity to tyrosine kinase inhibitors (TKIs) and mTOR inhibitors (mTORi) remain elusive. METHODS: We developed an in silico strategy by screening copy number variance (CNV) that was potentially related to TKI or mTORi sensitivity in ccRCC by reproducing the TCGA and GDSC datasets. Candidate genes should be both significantly prognostic and related to drug sensitivity or resistance, and were then validated in vitro. RESULTS: ADCYAP1 loss and GNAS gain were associated with sensitivity and resistance and to Cabozantinib, respectively. ACRBP gain and CTBP1 loss were associated with sensitivity and resistance and to Pazopanib, respectively. CDKN2A loss and SULT1A3 gain were associated with sensitivity and resistance and to Temsirolimus, respectively. CCNE1 gain was associated with resistance to Axitinib and LRP10 loss was associated with resistance to Sunitinib. Mutivariate analysis showed ADCYAP1, GNAS, and CCNE1 remained independently prognostic when adjusted for the rest. CONCLUSION: Here we show CNVs of several genes that are associated with sensitivity and resistance to commonly used TKIs and mTORi in ccRCC. Further validation and functional analyses are therefore needed.

Improved Transcatheter aortic valve implantation for aortic regurgitation using a new-type stent: the first preclinical experience.

BACKGROUND: In this study, we sought to evaluate the feasibility of improved transcatheter aortic valve implantation (TAVI) in noncalcified aortic valve by using the novel concept of double-layer ChenValve prosthesis. TAVI was initially considered as an alternative treatment for high-risk patients with aortic stenosis. However, non noncalcified aortic valve disease was considered as a contraindication to TAVI. METHODS: ChenValve prosthesis, which consisted of a self-expanding Nitinol ring, a balloon-expandable cobalt-chromium alloy stent and a biological valve, was implanted at the desired position under fluoroscopic guidance in a transapical approach through a 20F sheath in 10 goats. Aortic angiography was performed to measure the diameter of the aotic annulus and assess the performance of the artificial valve. The ultrasound was used to evaluate the regurgitation or paravalvular leakage and trans-prosthetic vascular flow velocity postoperatively. The aortogram and transthoracic echocardiography were applied to observe whether the valve stent was implanted at the desired position. RESULTS: ChenValve prosthesis was successfully transppical implanted in all animals. The aortogram and transthoracic echocardiography performed immediately after implantation revealed that the valve stent was implanted at the desired position. There was no significant paravalvular leakage, obstruction of coronary artery ostia, stent malpositioning or dislodgement occurred. CONCLUSIONS: This preliminary trial with the novel double-layer ChenValve prosthesis demonstrated the feasibility of improved TAVI in noncalcified aortic valve. The mechanism of Nitinol ring-guided locating the aortic sinus enables us to anatomically correct position the artifact valve. This improved strategy seems to make the TAVI process more safe and repeatable in noncalcified aortic valve.

Identification of candidate genes for human pituitary development by EST analysis.

BACKGROUND: The pituitary is a critical neuroendocrine gland that is comprised of five hormone-secreting cell types, which develops in tandem during the embryonic stage. Some essential genes have been identified in the early stage of adenohypophysial development, such as PITX1, FGF8, BMP4 and SF-1. However, it is likely that a large number of signaling molecules and transcription factors essential for determination and terminal differentiation of specific cell types remain unidentified. High-throughput methods such as microarray analysis may facilitate the measurement of gene transcriptional levels, while Expressed sequence tag (EST) sequencing, an efficient method for gene discovery and expression level analysis, may no-redundantly help to understand gene expression patterns during development. RESULTS: A total of 9,271 ESTs were generated from both fetal and adult pituitaries, and assigned into 961 gene/EST clusters in fetal and 2,747 in adult pituitary by homology analysis. The transcription maps derived from these data indicated that developmentally relevant genes, such as Sox4, ST13 and ZNF185, were dominant in the cDNA library of fetal pituitary, while hormones and hormone-associated genes, such as GH1, GH2, POMC, LHbeta, CHGA and CHGB, were dominant in adult pituitary. Furthermore, by using RT-PCR and in situ hybridization, Sox4 was found to be one of the main transcription factors expressed in fetal pituitary for the first time. It was expressed at least at E12.5, but decreased after E17.5. In addition, 40 novel ESTs were identified specifically in this tissue. CONCLUSION: The significant changes in gene expression in both tissues suggest a distinct and dynamic switch between embryonic and adult pituitaries. All these data along with Sox4 should be confirmed to further understand the community of multiple signaling pathways that act as a cooperative network that regulates maturation of the pituitary. It was also suggested that EST sequencing is an efficient means of gene discovery.

WITHDRAWN: LncRNA AK139128 promotes cardiomyocyte autophagy and apoptosis in myocardial hypoxia-reoxygenation injury.

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MiR-499a suppresses LPS-induced human vascular endothelial cell inflammatory response and apoptosis by regulating STAT1.

MicroRNAs (miRNAs) have been revealed to be involved in dysfunction and inflammatory conditions of vascular endothelial cells (ECs). However, the role of miR-499a in inflammatory responses and apoptosis of human umbilical vein endothelial cells (HUVECs) remains unclear. The expression of miR-499a and signal transducer and activator of transcription 1 (STAT1) was analyzed using quantitative real-time polymerase chain reaction or western blot assay, respectively. Cells apoptosis was determined by Flow cytometry. Western blot was used to evaluate the protein expression of STAT1, interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), B cell lymphoma (Bcl-2), Bcl-2 associated X (Bax) and Cleaved Caspase-3. The interaction between miR-499a and STAT1 was confirmed by bioinformatics analysis and luciferase reporter assay. The expression of miR-499a was significantly down-regulated, while the STAT1 level was obviously up-regulated in LPS-induced HUVECs. Overexpressed miR-499a inhibited LPS-activated expression of IL-6, VCAM-1 and ICAM-1, and protected HUVECs against LPS-induced apoptosis by suppressing the expression of Bax and cleaved caspase 3 expressions. However, STAT1 promoted LPS-induced inflammatory injury and apoptosis in HUVECs. In addition, STAT1 was predicted and confirmed to be a target of miR-499a, and rescue experiment indicated that STAT1 was involved in the miR-499a mediated protection on LPS-induced HUVECs inflammatory injury and apoptosis. MiR-499a protects HUVECs from LPS-induced inflammatory injury and apoptosis by regulating STAT1 expression, which providing a novel insight to assist researchers and clinicians in developing potential therapeutic strategies for sepsis.

Novel strategy of sirolimus plus thymalfasin and huaier granule on tumor recurrence of hepatocellular carcinoma beyond the UCSF criteria following liver transplantation: A single center experience.

Although liver transplantation (LT) lengthens the survival time of patients with hepatocellular carcinoma (HCC), LT patients exhibit a high recurrence rate; particularly those that had advanced HCC associated with the tumor biological characteristics and long-term application of immunosuppressants. A consensus on optimal prophylaxis and treatment for recurrent HCC following LT does not currently exist. The present study retrospectively analyzed data from 36 non-University of California at San Francisco criteria-eligible patients with advanced HCC who underwent LT, and then treated them with sirolimus (SRL)-based therapy with thymalfasin and huaier granules (SRL+, n=18), or with tacrolimus-based therapy (controls; n=18). The SRL+ group had significantly longer recurrence times (P=0.008) and survival times (P<0.0001) (OS, 1-year: 100%, 3-year: 94.4%, 5-year: 77.8%; DFS, 1-year: 88.9%, 3-year: 55.6%, 5-year: 50.0%). Furthermore, compared with pre-LT values and the control group, the SRL+ group had significantly lower serum α-fetoprotein (AFP) levels (both P<0.0001) and percentage of Forkhead box P3 (FoxP3)+ Treg lymphocytes (P<0.001) during the first year. In the SRL+ group, FoxP3+/cluster of differentiation (CD)8+ Treg lymphocyte percentages decreased significantly following LT (P<0.001); however, CD8+/CD3+ T-cells significantly increased (P<0.001). Levels of serum AFP and FoxP3+ Treg cells increased when tumors relapsed, and decreased to near-normal when relapse foci were cured or stabilized. SRL+ therapy may decrease AFP and Treg levels, while increasing CD8+ T cells, indicating an associated mechanism among them. In conclusion, SRL+ therapy appears to be safe and effective in preventing HCC recurrence following LT with no significant adverse events, and warrants further investigation.

[Immature dendritic cells phagocytosing human spleen cells treated by PUVA present the characteristics of regulatory dendritic cells].

Objective To investigate the effect of psoralen combined with A-band ultraviolet (PUVA)-treated human spleen lymphocytes on the phenotype and function of immature dendritic cells (imDCs). Methods Human peripheral blood mononuclear cells (PBMCs) were isolated and induced to produce DCs by interleukin-4 (IL-4) and recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF). On the sixth day, the imDCs were obtained and stimulated by lipopolysaccharide (LPS). One day later, mature DCs were harvested. Human spleen cells (SPs) were isolated and treated with PUVA to prepare apoptotic PUVA-SPs. Co-culture of imDCs with PUVA-SPs resulted in extracorporeal photochemotheraputic DCs (ecpDCs). Co-culture of imDCs with SPs resulted in SP-DCs. The expressions of CD11c, CD83 and CD86 were detected by flow cytometry. The levels of IL-10 and IL-12 in the supernatants of the above cells were determined by ELISA. Results The early apoptosis rate of PUVA-SPs was (94.21±3.75)%. There was no significant difference in the expressions of CD83 and CD86 between imDCs and ecpDCs. But the positive rates of CD83 and CD86 in ecpDCs were lower than those in DCs. However, the positive rates of CD83 and CD86 in SP-DCs were significantly higher than those of the imDCs. Conclusion The imDCs phagocytosing apoptotic human SPs present phenotype and function of regulatory DCs.

[Immature dendritic cells phagocytosing apoptotic human spleen cells treated with PUVA inhibits the maturation induced by LPS].

Objective To investigate whether lipopolysaccharide (LPS) can induce the maturation of immature dendritic cells (imDCs) which phagocytose apoptotic spleen lymphocytes. Methods Human peripheral blood mononuclear cells (PBMCs) were induced to produce DCs by interleukin 4 (IL-4) and recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF). Human spleen cells (hSPs) were isolated and treated with psoralen combined with ultraviolet A(PUVA) to obtain apoptotic PUVA-hSPs. Co-culture of imDCs with PUVA-hSPs resulted in extracorporeal photochemotherapeutic dendritic cells (ecpDCs). The imDCs and ecpDCs were collected and stimulated by 10 ng/mL LPS for 1 day. The expressions of CD11c, CD83 and CD86 were detected by flow cytometry. The level of IL-10 in the supernatants of the above cells was detected by ELISA. Results There was no significant difference in the expressions of CD83 and CD86 between ImDCs and ecpDCs. However, the positive rates of CD83 and CD86 in the imDCs stimulated by LPS were significantly higher than those in the ecpDCs treated by LPS. The level of IL-10 in imDCs culture supernatant was lower than that in ecpDCs. The level of IL-10 in LPS-stimulated imDCs was lower than that in LPS-stimulated ecpDCs. Conclusion Both imDCs and ecpDCs showed immature phenotype, but ecpDCs can inhibit the maturation of DC induced by LPS.

Sirolimus treatment for cirrhosis or hepatocellular carcinoma patients accompanied by psoriasis after liver transplantation: A single center experience.

There is currently no consensus on the most suitable therapeutic approach for psoriasis (PS) co-existing with posthepatic cirrhosis (PCs) and hepatocellular carcinoma (HCC) following liver transplantation (LT). The present study provides an analysis of the therapeutic experience of such patients. Five LT recipients (two with PC and three with HCC) with accompanying PS were included. The induction program consisted of methylprednisolone plus basiliximab treatment. The initial postoperative treatment scheme consisted of tacrolimus (FK506) plus mycophenolate mofetil (MMF) and hormone; the latter was withdrawn 1 week after LT. The patients with PC had been using FK506 with or without a postoperative MMF program; the patients with HCC and recurrence of PS had been switched to a sirolimus (SRL)-based replacement therapy. Furthermore, all patients received anti-hepatitis B virus (HBV) therapy. The patients were followed up after 8.3±1.5 years. There was a positive correlation between HBV-DNA copy numbers, and psoriatic area and severity index (PASI) scores (r=0.97; P=0.006). The PASI scores were decreased significantly at 6 months following surgery compared with pre-transplantation (P<0.05). The patients who had received the FK506-based treatment experienced PS recurrence two years post-transplantation. The PASI scores increased significantly (P<0.05) and then declined gradually, maintaining a stable level (P<0.05) by 1 year after switching to the SRL-based treatment. The patients who had received the SRL-based treatment exhibited no recurrence of PS. The results of the present study suggest that SRL therapy provides a promising novel treatment method for patients with PS following LT that may be superior to tacrolimus treatment. When co-existing HBV is present pre-transplantation, regular injection of human hepatitis B immunoglobulin should be used to prevent the HBV from relapsing or aggravating the PS.

[Triplet anti-tumor therapy based on thymosin α-1 attenuates incidence of hepatoma and serum alpha-fetoprotein level in rat hepatoma model].

OBJECTIVE: To explore the impact of triple anti-tumor therapy based on thymosin α1 (Tα1) combined with Huaier granule(HG) and sirolimus on the level of serum alpha-fetoprotein (AFP) in rat models of liver cancer. METHODS: Ninety Sprague-Dawley rats were randomly divided into triple anti-tumor therapy group, Tα1 group, HG group, sirolimus group, positive control and blank control groups, with 15 rats in each group. Except the blank control group, the rats in the other groups were induced using diethylnitrosamine (DEN) to establish liver cancer models. After DEN treatment, the triple therapy group underwent 0.8 mg/kg Tα1 subcutaneous injection (from once a day for two weeks to twice a week since the third week), 0.35 g/kg HG gavage (three times a day) and 1 mg/kg sirolimus gavage (once a day). The dose of the rest single drug groups were the same with that of the triple therapy group. The positive control and blank control groups were not treated with the drugs. The treatment lasted 20 weeks. Then, the behavior of the rats were observed at the different time points, and the level of serum AFP in the rats were detected at 6, 16, 18, 20 weeks, respectively. RESULTS: The typical symptoms of liver cancer were seen in the DEN-induced rats at 16 weeks. Since the tenth week, 6 rats died one after another. Pathological section of rat liver tissue suggested that the rat models were established successfully. According to the incidence rate of liver cancer and the survival rate at 20 weeks, the triple anti-tumor therapy was significantly superior to the single drug treatments. In addition, the triple anti-tumor therapy significantly reduced the level of serum AFP in the rats. CONCLUSION: The triple anti-tumor therapy can significantly prolong the survival time of rats with liver cancer, decrease the cancer incidence rate and the level of serum AFP.