Secure optical communication system based on polarization regulation of the data fragmentation multipath transmission technology.

We propose and demonstrate a data fragment multipath transmission scheme to achieve a secure optical communication based on polarization regulation. A dual-polarization Mach-Zehnder modulator (DPMZM) is driven by digital signals which are scattered by field-programmable gate array (FPGA) and transmitted in multiple paths. By utilizing two orthogonal polarization states, we have achieved a signal transmission under different optical parameters, and the transmission rate of the two paths can reach over 10 Gbps through a 20 km fiber with 2.5 Gbps hopping rate. In addition, we establish a theoretical model to analyze the security of the system and simulate brute force cracking; the probability of cracking the minimum information unit is 1.53 × 10-53. This proves that it is difficult to obtain a user data even using the fastest computers. Our scheme has provided, to our knowledge, a new approach for physical layer security.

Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis.

BACKGROUND: Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood. METHODS: Senescence-associated beta-galactosidase staining, immunohistochemistry, and TUNEL staining were used to assess senescence and apoptosis, respectively. Flow cytometry was employed to evaluate mitochondrial membrane potential (MMP) and apoptosis in granulosa cells lines (KGN), and macrophages phagocytosis. After a 2-month treatment with low molecular weight Chitosan (LMWC), ovarian tissues from mice were collected for comprehensive analysis. RESULTS: Compared with the liver and uterus, the ovary displayed accelerated aging in an age-dependent manner, which was accompanied by elevated levels of inflammatory factors and apoptotic cells, and impaired macrophage phagocytic activity. The aged KGN cells exhibited elevated reactive oxygen species (ROS) and apoptotic levels alongside decreased MMP. H2O2-induced aging macrophages showed reduced phagocytosis function. Moreover, there were excessive aging macrophages with impaired phagocytosis in the follicular fluid of patients with diminished ovarian reserve (DOR). Notably, LMWC administration alleviated ovarian aging by enhancing macrophage phagocytosis and promoting tissue homeostasis. CONCLUSIONS: Aging ovarian is characterized by an accumulation of aging and apoptotic granulosa cells, an inflammatory response and macrophage phagocytosis dysfunction. In turn, impaired phagocytosis of macrophage contributes to insufficient clearance of aging and apoptotic granulosa cells and the increased risk of DOR. Additionally, LMWC emerges as a potential therapeutic strategy for age-related ovarian dysfunction.

Functionalized graphene oxide as a nanocarrier for delivering oridonin to improve anti-breast cancer cell activity.

In this study, a targeted nanocarrier was developed by functionalizing graphene oxide with polyethyleneimine and folic acid, intended for loading oridonin. The nanocarrier was successfully synthesized and characterized using an ultraviolet spectrum, Fourier transform infrared spectroscopy and scanning electron microscopy. The nanocarrier demonstrated a remarkable oridonin loading capacity, reaching 424.8 µg/mg, as determined by ultra-high performance liquid chromatography. In vitro drug release experiments exhibited a pH-dependent release profile, with a higher cumulative release in an acidic environment. The release mechanism followed the Ritger-Peppas equation model. Cytotoxicity assays indicated minimal toxicity of the nanocarrier. Enhanced cellular uptake by MCF7 cells was observed for carriers functionalized with folate and polyethyleneimine. These findings highlight the potential of functionalized graphene oxide as a promising carrier for oridonin delivery in biomedical applications.

Hypoxia-mediated chemotaxis and residence of macrophage in decidua by secreting VEGFA and CCL2 during normal pregnancy.

In brief: Hypoxia is vital for the establishment of the maternal-fetal interface during early pregnancy. This study shows that decidual macrophages (dMφ) could be recruited and reside in decidua under the regulation of hypoxia/VEGFA-CCL2 axis. Abstract: Infiltration and residence of decidual macrophages (dMφ) are of great significance to pregnancy maintenance for their role in angiogenesis, placental development, and inducing immune tolerance. Besides, hypoxia has now been acknowledged as an important biological event at maternal-fetal interface in the first trimester. However, whether and how hypoxia regulates biofunctions of dMφ remain elusive. Herein, we observed increased expression of C-C motif chemokine ligand 2 (CCL2) and residence of macrophages in decidua compared to secretory-phase endometrium. Moreover, hypoxia treatment on stromal cells improved the migration and adhesion of dMφ. Mechanistically, these effects might be mediated by upregulated CCL2 and adhesion molecules (especially ICAM2 and ICAM5) on stromal cells in the presence of endogenous vascular endothelial growth factor-A (VEGFA) in hypoxia. These findings were also verified by recombinant VEGFA and indirect coculture, indicating that the interaction between stromal cells and dMφ in hypoxia condition may facilitate dMφ recruitment and residence. In conclusion, VEGFA derived from a hypoxic environment may manipulate CCL2/CCR2 and adhesion molecules to enhance the interactions between dMφ and stromal cells and thus contribute to the enrichment of macrophages in decidua early during normal pregnancy.

IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/ß-catenin pathway in fetal growth restriction.

Background: Fetal growth restriction (FGR) is characterized by restricted fetal growth and dysregulated placental development. The etiology and pathogenesis still remain elusive. IL-27 shows multiple roles in regulating various biological processes, however, how IL-27 involves in placentation in FGR pregnancy hasn't been demonstrated. Methods: The levels of IL-27 and IL-27RA in FGR and normal placentae were determined by immunohistochemistry, western blot and RT-PCR. HTR-8/SVneo cells and Il27ra-/- murine models have been adopted to evaluate the effects of IL-27 on the bio-functions of trophoblast cells. GO enrichment and GSEA analysis were performed to explore the underlying mechanism. Findings: IL-27 and IL-27RA was lowly expressed in FGR placentae and administration of IL-27 on HTR-8/SVneo could promote its proliferation, migration and invasion. Comparing with wildtypes, Il27ra-/- embryos were smaller and lighter, and the placentae from which were poorly developed. In mechanism, the molecules of canonical Wnt/ß-catenin pathway (CCND1, CMYC, SOX9) were downregulated in Il27ra-/- placentae. In contrast, the expression of SFRP2 (negative regulator of Wnt) was increased. Overexpression of SFRP2 in vitro could impair trophoblast migration and invasion capacity. Interpretation: IL-27/IL-27RA negatively regulates SFRP2 to activate Wnt/ß-catenin, and thus promotes migration and invasion of trophoblasts during pregnancy. However, IL-27 deficiency may contribute to the development of FGR by restricting the Wnt activity.

Preparation, characterization, and pharmacokinetics of oridonin-loaded liposomes.

The aim of this study was to prepare oridonin liposomes and evaluate the physicochemical characteristics and pharmacokinetics in rats. A three-level, three-factor Box-Behnken design was used to optimize the preparation of oridonin liposomes. A highly sensitive high-performance liquid chromatographic quantification method using ultraviolet detection was established and validated for the determination of oridonin in rat plasma. Twelve Sprague-Dawley rats were randomly assigned and injected with 15 mg/kg of oridonin or oridonin liposomes via the tail vein. Pharmacokinetic parameters were estimated using a compartmental modeling approach using PKsolver software. The optimum conditions were as follows: soybean phospholipids/cholesterol ratio, 3.9:1; soybean phospholipids/drug ratio, 8.5:1; and soybean phospholipid concentration, 1.1%. Under these conditions, the mean particle size, polydispersity index, zeta potential, and encapsulation efficiency of oridonin liposomes were 170.5 nm, 0.246, -30.3 mV, and 76.15%, respectively. The pharmacokinetic results showed that liposomes could significantly prolong the elimination half-life (from 2.88 ± 0.55 to 13.67 ± 3.52 h), increase the area under the concentration-time curve (from 1.65 ± 0.17 to 6.22 ± 0.83 µg h/ml), and decrease the clearance (from 6.62 ± 1.38 to 1.96 ± 0.24 L/kg h). The oridonin liposomes increased the elimination half-life and area under the concentration-time curve and provided a reference for the development of drugs with a short half-life.

Synaptic control of spinal GRPR+ neurons by local and long-range inhibitory inputs.

Spinal gastrin-releasing peptide receptor-expressing (GRPR+) neurons play an essential role in itch signal processing. However, the circuit mechanisms underlying the modulation of spinal GRPR+ neurons by direct local and long-range inhibitory inputs remain elusive. Using viral tracing and electrophysiological approaches, we dissected the neural circuits underlying the inhibitory control of spinal GRPR+ neurons. We found that spinal galanin+ GABAergic neurons form inhibitory synapses with GRPR+ neurons in the spinal cord and play an important role in gating the GRPR+ neuron-dependent itch signaling pathway. Spinal GRPR+ neurons also receive inhibitory inputs from local neurons expressing neuronal nitric oxide synthase (nNOS). Moreover, spinal GRPR+ neurons are gated by strong inhibitory inputs from the rostral ventromedial medulla. Thus, both local and long-range inhibitory inputs could play important roles in gating itch processing in the spinal cord by directly modulating the activity of spinal GRPR+ neurons.

Factors influencing career success of clinical nurses in northwestern China based on Kaleidoscope Career Model: Structural equation model.

AIM: To explore the relationships among self-efficacy, information literacy, social support and career success of clinical nurses and identify factors influencing clinical nurses' career success in northwestern China. BACKGROUND: Understanding the influencing factors of career success is important for the professional development of nurses and the improvement of clinical nursing quality. Many influencing factors of career success have been identified, but there is no large-scale research on the relationships among self-efficacy, information literacy, social support and career success of clinical nurses based on Kaleidoscope Career Model. Studies examining the association of the four factors remain limited. METHODS: A total of 3011 clinical nurses from 30 hospitals in northwestern China were selected in the cross-sectional survey, and the response rate was 94.71%. The clinical nurses completed the online self-report questionnaires including self-efficacy, information literacy, social support rating scale and career success scale. The data were analysed by SPSS23.0 statistical software using t test, analysis of variance, Pearson's correlation and multiple linear regression. Structural equation model (SEM) was used to analyse the influencing factors of career success using Mplus 8.3. RESULTS: The career success of clinical nurses in northwestern China was at a medium level. The linear multivariate regression analysis showed that self-efficacy (ß = .513), social support (ß = .230), information support (ß = .106), information consciousness (ß = -.097), information knowledge (ß = .067), information ethics (ß = -.053), hospital grade (ß = .118), marital status (ß = -.071) and age (ß = -.037) entered regression equation of clinical nurses' career success (all P < .05). SEM results showed that the career success was negatively correlated with demographic characteristics and positively correlated with social support and self-efficacy. CONCLUSION: Demographic characteristics, self-efficacy, social support and information literacy are the influencing factors of nurses' career success, which should be considered in the process of promoting nurses' career success. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers need to acknowledge the significance of nurses' career success both for the realization of their own value and for the improvement of clinical nursing quality. They should encourage nurses to enhance self-efficacy and render more social support through incentive policies and foster nurses' information literacy through information technology training so as to improve their career success.

Career identity and career success among Chinese male nurses: The mediating role of work engagement.

AIM: This study aimed to investigate the effect of career identity on career success among Chinese male nurses and to examine the mediating role of work engagement in this relationship. BACKGROUND: Recently, with the development of the nursing career, male nurses take up a higher share and play a more important role in the nursing team. With its own particularity and advantages, this group's stability closely relates to the future of the nursing team. Therefore, promoting the career success of the male nurses is essential to the nursing team development. METHODS: The data were collected in China. A sample of 557 male nurses completed measures of career identity, work engagement and career success scale. Structural equation model was adopted to verify the research hypotheses. RESULTS: Career identity was significantly and positively related to male nurses' work engagement and career success (p < .01). And work engagement partially mediated the association between career identity and career success. CONCLUSION: Career identity is critical to predicting and enhancing male nurses' career success. Work engagement plays an intervening mechanism explaining how career identity promotes career success among male nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing management should minimize the impact of the traditional concept, implement the gender equality and provide moderate care for male nurses to facilitate balanced development of gender by upgrading the management system. The administrators should carry out skill training based on male nurses' features and the need of the department. Given full play to their respective advantages, male nurses will make great progress in professional development and achieve greater career identity and work engagement. Meanwhile, the further exploration of better incentive mechanism also makes sense in improving career identity and work engagement by the reform of performance appraisal mechanism and salary adjustment according to their ability.

HIF1A-induced heme oxygenase 1 promotes the survival of decidual stromal cells against excess heme-mediated oxidative stress.

Heme oxygenase 1 (HO-1, encoded by the HMOX1 gene) is the rate-limiting enzyme that catalyzes heme degradation, and it has been reported to exert antioxidative effects. Recently, decidualization has been reported to confer resistance to environmental stress signals, protecting against oxidative stress. However, the effects and regulatory mechanism of HO-1 in decidual stromal cells (DSCs) during early pregnancy remain unknown. Here, we verified that the levels of HO-1 and heme in DSCs are increased compared with those in endometrial stromal cells. Additionally, the upregulation of HIF1A expression led to increased HMOX1 expression in DSCs possibly via nuclear factor erythroid 2-related factor (encoded by the NFE2L2 gene). However, addition of the competitive HO-1 inhibitor zinc protoporphyrin IX resulted in an increase in HIF1A expression. Hydrogen peroxide (H2O2) induced the production of reactive oxygen species (ROS), decreased the cell viability of DSCs in vitro, and upregulated the level of heme. As an HO-1 inducer, cobalt protoporphyrin IX decreased ROS production and significantly reversed the inhibitory effect of H2O2 on cell viability. More importantly, patients with unexplained spontaneous abortion had low levels of HO-1 that were insufficient to protect against oxidative stress. This study suggests that the upregulation of HO-1 expression via HIF1A protects DSCs against excessive heme-mediated oxidative stress. Furthermore, the excessive oxidative stress injury and impaired viability of DSCs associated with decreased HO-1 expression should be associated with the occurrence and/or development of spontaneous abortion.

A positive COX-2/IL-1ß loop promotes decidualization by upregulating CD82.

A successful pregnancy requires sufficient decidualization of endometrial stromal cells (ESCs). CD82, a metastasis suppressor, is a critical regulator for trophoblast invasion but the effect in decidualization was largely unknown. Here we reported that there was a high level of CD82 in DSC by the immunohistochemistry staining and flow cytometer analysis. Stimulation with prostaglandin E2 (PGE2) elevated the expression of CD82 in ESCs. In contrast, celecoxib, a selective COX-2 inhibitor, significantly downregulated the expression of CD82 in decidual stromal cells (DSCs). Bioinformatics analysis and further research showed that recombinant human interleukin (IL)-1ß protein (rhIL-1ß) upregulated CD82 in ESCs. Of note, blocking IL-1ß signaling with anti-human IL-1ß neutralizing antibody could reverse the stimulatory effect of PGE2 on CD82 in ESCs. Silencing CD82 resulted in the decease of the decidualization markers PRL and IGFBP1 mRNA levels in DSCs. More importantly, we observed rhIL-1ß also upregulated the expression of COX-2, and the upregulation of PRL and IGFBP1 induced by rhIL-1ß could be abolished by celecoxib in ESCs or CD82 deficiency in DSCs. This study suggests that CD82 should be a novel promotor for decidualization under a positive regulation of the COX-2/PGE2/IL-1ß positive feedback loop.

The influence of hypoglycemia on the specific quality of life in type 2 diabetes mellitus: a comparative cross-sectional study of diabetics with and without hypoglycemia in Xi'an, China.

PURPOSE: This study aims to explore the incidence of hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and the influence of hypoglycemia on the specific quality of life in T2DM patients. METHODS: It was a comparative cross-sectional study consisting of 519 T2DM patients in Xi'an, China and patients were investigated by self-reported hypoglycemia and specific quality of life questionnaires from September 2019 to January 2020. Descriptive analysis, t-test, Chi-square test, hierarchical regression analysis and stepwise multiple regression analysis were applied to assess the influence of hypoglycemia on the specific quality of life. RESULTS: The incidence of hypoglycemia in T2DM patients was 32.18%. The mean score of specific quality of life in diabetes without hypoglycemia was 57.33 ± 15.36 and was 61.56 ± 17.50 in those with hypoglycemia, which indicated that hypoglycemia had a serious impact on the quality of life of diabetics (t = - 5.172, p = 0.000). In the Univariate analysis of specific quality of life, age, education background, marital status, living status, duration of diabetes, monthly income per capita were independent and significant factors associated with specific quality of life of two groups of T2DM patients (p < 0.05). In the hierarchical regression analysis, the duration of the diabetes more than 11 years and the frequency of hypoglycemia more than 6 times in half a year entered the equation of specific quality of life of 519 diabetics respectively (p < 0.001). In multiple linear regression analysis, age, marital status and income all entered the regression equation of quality of life of the two groups (p < 0.05). CONCLUSION: Hypoglycemia will have a serious impact on the quality of life of T2DM patients. In order to improve the living quality in diabetics, effective measurements should be taken to strengthen the management of blood glucose and to avoid hypoglycemia.

[Role of 8-allyl Garcinol in the Chemoprevention of Oral Squamous Cell Carcinoma].

Objective To evaluate the chemopreventive effects of 8-allyl garcinol on oral squamous cell carcinoma(OSCC).Methods OSCC cell line CAL27 were cultured and treated with different concentrations of garcinol or 8-allyl garcinol. Their effects on the biological behaviors of OSCC cell line CAL27 were measured by MTT assay,clony formation assay,scratch migration assay,and flow cytometry with Annexin V-FITC/PI staining assay. We established DMBA-induced hamster cheek pouch models of dysplasia. While the negative control group was not treated,the positive group was treated with 0.5% DMBA solution tropically to the left cheek pouch three times per week for three consecutive weeks. The other four groups received 0.5 mmol/L or 1.0 mmol/L garcinol or 8-allyl garcinol respectively three times within the following two weeks after DMBA treatment. Hamsters were sacrificed at the fifth week to obtain tissue samples of the left cheek pouch. The samples were examined by histopathology and BrdU immunohistochemisty.Results MTT assay showed that both garcinol and 8-allyl garcinol inhibited the proliferation of CAL27 cells in a concentration-and time-dependent manner. The half maximal inhibitory concentration(IC50)of 8-allyl garcinol[(13.13±2.55)µmol/L] was significantly lower than garcinol[(32.20±3.24)µmol/L;t=8.008,P=0.001]. Comparing the two grougs of medicine in the same concentration,the inhibiting proliferation effects 8-allyl garcinol had significantly stronger effect in inhibiting proliferation than garcinol when the same dose was applied,and the difference was largest at the concentrations of 10(24 h:t=8.012,P=0.001;48 h:t=5.939,P=0.001;72 h:t=12.551,P=0.001)and 20 µmol/L(24 h:t=8.887,P=0.001;48 h:t=9.324,P=0.002;72 h:t=5.361,P=0.002). The clone formation assay showed the clone formation rates after the treatment with 20 µmol/L garcinol and 20 µmol/L 8-allyl garcinol were(44.1±0.4)% and(23.6±0.6)%,respectively,which were significantly lower than those after treatment with 10 µmol/L garcinol[(55.6±2.8)%;t=6.894,P=0.019] and 10 µmol/L 8-allyl garcinol[(31.0±0.6)%;t=15.556,P=0.001]. The inhibiting effects of 8-allyl garcinol at the concentrations of 10 µmol/L(t=14.682,P=0.003)and 20 µmol/L(t=51.514,P=0.001)were significantly stronger than garcinol.Scratch test showed the relative cell migration rates after treatment with 10 and 20 µmol/L garcinol for 12 hours were(16.00±4.55)%(t=3.139,P=0.026)and(3.00±3.16)%(t=6.608,P=0.001),respectively,which were lower than negative control [(30.33±7.64)%]. The relative cell migration rates after treatment with 10 and 20 µmol/L 8-allyl garcinol for 12 hours were(16.25±3.86)%(t=3.245,P=0.023)and(6.00±2.65)%(t=5.214,P=0.006),respectively,which were also lower than negative control[(30.33±7.64)%]. In addition,the relative cell migration rates after treatment with 10 and 20 µmol/L garcinol for 24 hours were(23.75±4.57)%(t=4.718,P=0.005)and(5.75±1.50)%(t=10.432,P=0.001),respectively,which were lower than negative control[(45.33±7.64)%]. The relative cell migration rates after treatment with 10 and 20 µmol/L 8-allyl garcinol for 24 hours were(23.50±2.38)%(t=5.529,P=0.003)and(11.67±2.31)%(t=7.308,P=0.002),respectively,which were also lower than negative control[(45.33±7.64)%]. Furthermore,the relative cell migration rate after treatment with 20 µmol/L garcinol for 24 hours was significantly lower than after treatment with 8-allyl garcinol(t=4.151,P=0.009). The apoptosis experiments showed that the early apoptosis rate of CAL27 cells was(5.00±0.10)% after treatment with 10 µmol/L garcinol,which was significantly higher than negative control[(1.57±0.21)%;F=70.950,P=0.001]. The early and late apoptosis rates of CAL27 cells were(5.90±0.78)%(t=39.384,P=0.001)and(9.73±1.67)%(t=10.101,P=0.001),respectively,after treatment with 20 µmol/L garcinol,which were also significantly higher than negative control. The early apoptosis rate of CAL27 cells was(4.63±1.16)% after treatment with 8-allyl garcinol,which was significantly higher than negative control(t=4.511,P=0.041). The effects of 8-allyl garcinol in promoting cell apoptosis were weaker than garcinol(10 µmol/L:t=5.982,P=0.004;20 µmol/L:t=8.578,P=0.001). The histopathological test also showed that the hyperplastic areas of oral mucosal epithelium in hamsters after treatment with 0.5 mmol/L garcinol(t=2.546,P=0.031),0.5 mmol/L 8-allyl garcinol(t=3.485,P=0.008),1.0 mmol/L garcinol(t=4.556,P=0.001),and 1.0 mmol/L 8-allyl garcinol(t=5.393,P=0.001)were significantly smaller than positive control. The dysplasia areas of oral mucosal epithelium in hamsters after treatment with 0.5 mmol/L 8-allyl garcinol(t=2.130,P=0.046),1.0 mmol/L garcinol(t=3.434,P=0.010),and 1.0 mmol/L 8-allyl garcinol(t=4.518,P=0.004)were also smaller than positive control;1.0 mmol/L garcinol group(t=2.793,P=0.023)and 1.0 mmol/L 8-allyl garcinol group(t=4.997,P=0.001)were smaller than 0.5 mmol/L garcinol treatment group. Immunohistochemical staining of BrdU showed that the BrdU-labeled indicators were significantly lower in negative control group(t=7.563,P=0.001),0.5 mmol/L garcinol(t=2.862,P=0.029),0.5 mmol/L 8-allyl garcinol(t=4.693,P=0.002),1.0 mmol/L garcinol(t=5.071,P=0.002),and 1.0 mmol/L 8-allyl garcinol(t=5.133,P=0.001)when compared with the positive control. The BrdU-labeled indicators in 0.5 mmol/L 8-allyl garcinol(t=3.724,P=0.007),1.0 mmol/L garcinol(t=7.000,P=0.001),and 1.0 mmol/L 8-allyl garcinol(t=4.413,P=0.003)were also significantly lower than in 0.5 mmol/L garcinol group.Conclusions 8-allyl garcinol could inhibit the proliferation and migration of OSCC cell line CAL27 and promotes apoptosis. It also has prominent inhibitory effects on DMBA-induced hamster cheek pouch dysplasia. However,the specific effects are slightly different from garcinol.

Conversion to resectability using transcatheter arterial chemoembolization alternating with mFOLFOX6 in patients with colorectal liver metastases.

BACKGROUND: Colorectal cancer is one of the most common malignancies in the world, and about 25% of colorectal cancer patients present with colorectal cancer liver metastases (CRCLM) even at new diagnosis. The study was to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) alternating with mFOLFOX6 in Chinese patients with unresectable CRCLM. MATERIALS AND METHODS: In this study, by combining the systemic and regional treatment, the resectability rate, overall survival, and progression-free survival were measured with addition of TACE. Included patients had Eastern Cooperative Oncology Group performance status 0-2. Sixty-two patients received mFOLFOX6 plus one TACE after 2 weeks of chemotherapy; after 2 weeks, the next periodical treatment repeated. Patients received operation when the liver metastases were converted to resectability or severe tumor-associated complications occurred. RESULTS: We found that 28 patients (45.2%) patients received operation after the treatment of TACE combined with systemic chemotherapy. The median time from initial treatment to the operation was 6 months. The median follow-up period was 41 months in all the patients. The 3-year survival rate of resected patients and unresected patients was 54% and 17%, respectively. Post-TACE syndrome was the major adverse reaction (81%). Other adverse reactions were neutropenia, nausea, and neurotoxicity. No patient died of the adverse reactions. The resection rate was related to hepatic segments and vasculature involvement. CONCLUSION: Taken together, TACE alternating with mFOLFOX6 has been proved to be safe and effective for CRCLM treatment to improve resection rate and prolong the survival time.

[Serum levels of interleukin-38 and interleukin-1ß in the acute phase of Kawasaki disease in children].

OBJECTIVE: To study the expression of serum cytokines, interleukin-38 (IL-38) and interleukin-1ß (IL-1ß) in the acute phase of Kawasaki disease (KD) in children and the association of IL-38 and IL-1ß with inflammatory response in the acute phase and the development of coronary artery lesion (CAL). METHODS: A total of 40 children with KD who were hospitalized in the hospital between July 2015 and June 2016 were enrolled, with 21 children in the CAL group and 19 in the non-CAL (NCAL) group. Thirty healthy children and 19 children with infection and pyrexia, who were matched for sex and age, were enrolled as healthy control group and pyrexia control group respectively. ELISA was used to measure the serum levels of IL-38 and IL-1ß in the 40 children in the acute phase of KD. Spearman's rank correlation analysis was used to investigate the correlations of IL-1ß and IL-38 with interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), triglyceride (TG), and total cholesterol (TC). RESULTS: The serum level of IL-38 in the children in the acute phase of KD was significantly lower than that in the healthy control group (P<0.05), but significantly higher than that in the pyrexia control group (P<0.05). There was no significant difference in the level of IL-38 between the CAL and NCAL groups (P>0.05). The children in the acute phase of KD had a significantly higher level of IL-1ß than the healthy control group (P<0.05), while there was no significant difference between this group and the pyrexia control group (P>0.05). There was also no significant difference in the level of IL-1ß between the CAL and NCAL groups (P>0.05). Serum IL-1ß and IL-38 levels were not correlated with serum levels of CRP, ESR, PCT, IL-6, and NT-ProBNP or blood lipids (TG and TC) (P>0.05). CONCLUSIONS: IL-38 is involved in an inflammatory response in the acute phase of KD and may exert an anti-inflammatory effect, which is opposite to the effect of IL-1ß to promote inflammatory response. However, there is no significant correlation between these two cytokines and the development of CAL in KD.

The C8 side chain is one of the key functional group of Garcinol for its anti-cancer effects.

Garcinol from the fruit rind of Garcinia indica shows anti-carcinogenic and anti-inflammatory properties, but its mechanism and key functional groups were still need to be identified. Our previous computer modeling suggested that the C8 side chain of Garcinol is so large that it may influence the bioactivity of the compound. 8-Me Garcinol, a derivative of Garcinol in which the bulky side chain at the C8 position of Garcinol is replaced with a much smaller methyl group, was synthesized through a 12-step procedure starting from 1,3-cyclohexanedione. The antitumor activity of Garcinol and 8-Me Garcinol was evaluated in vitro by MTT, cell cycle and cell apoptosis assays. The results showed that 8-Me Garcinol had weaker inhibitory activity on cells proliferation, and little effects on cell cycle and apoptosis in oral cancer cell line SCC15 cells when compared with Garcinol. All of the results indicated 8-Me Garcinol exerts weaker antitumor activity than Garcinol, and the C8 side chain might be an important active site in Garcinol. Changing the C8 side chain will affect the inhibitory effect of Garcinol.

What is the impact of n-3 PUFAs on inflammation markers in Type 2 diabetic mellitus populations?: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To explore the possible role of n-3 polyunsaturated fatty acids (PUFAs) in lowering inflammation markers in individuals with type 2 diabetes mellitus. METHODS: PubMed, CNKI and Cochrane databases were searched until December 30, 2015; references from papers or reviews were also retrieved and screened. Screening was performed by two independent researchers, and randomized controlled trials reporting the specific n-3 PUFA type, dose, frequency, and duration of treatment, as well as the baseline and follow-up concentrations of inflammation markers, including interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP), were selected for final analysis. Data analysis was performed using RevMan 5.2 software. RESULTS: Eight studies involving 955 participants were included; all reported CRP. Only one included study reported IL-2 or IL-6 while two studies reported TNF-α. N-3 PUFAs significantly reduced CRP concentration compared with control [SMD 95 % CI, 1.90 (0.64, 3.16), Z = 2.96, P = 0.003, random effect model]. CONCLUSIONS: N-3 PUFAs decrease CRP concentration in type-2 diabetes mellitus. However, larger and rigorously designed RCTs are required to confirm this finding and extend it into other inflammatory biomarkers.

13,14-Dihydroxy groups are critical for the anti-cancer effects of garcinol.

In the presence of K2CO3/Cs2CO3 (molar ratio 10:1), garcinol was subjected to methylation by reaction with iodomethane at room temperature to afford 13,14-dimethoxy garcinol. The methylated garcinol derivative was screened against oral cancer cell line SCC15 for cell proliferation and apoptosis. 13,14-Dimethoxy garcinol showed weaker inhibitory activity on SCC15 cell growth than garcinol, and had little effect on cell cycle and apoptosis of SCC15, whereas garcinol effectively induced cell cycle arrest and cell apoptosis. Meanwhile, the ELISA data showed that the inhibitory effect of garcinol on 5-Lox pathway was more potent than 13,14-dimethoxy garcinol (P<0.05). All these results have confirmed the important role of 13,14-dihydroxy groups for anti-cancer effects of garcinol.

Layer-by-Layer Assembly of Renal-Targeted Polymeric Nanoparticles for Robust Arginase-2 Knockdown and Contrast-Induced Acute Kidney Injury Prevention.

The mitochondrial enzyme arginase-2 (Arg-2) is implicated in the pathophysiology of contrast-induced acute kidney injury (CI-AKI). Therefore, Arg-2 represents a candid target for CI-AKI prevention. Here, layer-by-layer (LbL) assembled renal-targeting polymeric nanoparticles are developed to efficiently deliver small interfering RNA (siRNA), knockdown Arg-2 expression in renal tubules, and prevention of CI-AKI is evaluated. First, near-infrared dye-loaded poly(lactic-co-glycolic acid) (PLGA) anionic cores are electrostatically coated with cationic chitosan (CS) to facilitate the adsorption and stabilization of Arg-2 siRNA. Next, nanoparticles are coated with anionic hyaluronan (HA) to provide protection against siRNA leakage and shielding against early clearance. Sequential electrostatic layering of CS and HA improves loading capacity of Arg-2 siRNA and yields LbL-assembled nanoparticles. Renal targeting and accumulation is enhanced by modifying the outermost layer of HA with a kidney targeting peptide (HA-KTP). The resultant kidney-targeting and siRNA loaded nanoparticles (PLGA/CS/HA-KTP siRNA) exhibit proprietary accumulation in kidneys and proximal tubular cells at 24 h post-tail vein injection. In iohexol-induced in vitro and in vivo CI-AKI models, PLGA/CS/HA-KTP siRNA delivery alleviates oxidative and nitrification stress, and rescues mitochondrial dysfunction while reducing apoptosis, thereby demonstrating a robust and satisfactory therapeutic effect. Thus, PLGA/CS/HA-KTP siRNA nanoparticles offer a promising candidate therapy to protect against CI-AKI.

Orexin Neurons to Sublaterodorsal Tegmental Nucleus Pathway Prevents Sleep Onset REM Sleep-Like Behavior by Relieving the REM Sleep Pressure.

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.