Moringa isothiocyanate-1 mitigates the damage of oxidative stress and apoptosis in diabetic nephropathy mice.

OBJECTIVE: Diabetic nephropathy (DN) is a prevalent cause of end-stage kidney disease worldwide. Moringa isothiocyanate-1 (MIC-1) has shown potential for DN management, however, the exact mechanisms remain unclear. This research intended to evaluate the impact and mechanism of MIC-1 on DN. METHODS: Six C57BLKS/J-db/m mice served as controls. Eighteen C57BLKS/J-db/db mice were randomly separated into three groups: db/db, db/db + irbesartan (IBS), and db/db + MIC-1. Three weeks post-drug administration, the body weight and kidney weight of mice in each group were measured. Concurrently, serum creatinine (Scr), urine albumin, insulin, glycosylated hemoglobin (GHb), oxidative stress-, and inflammatory-related factors were determined. Additionally, the pathological injury, apoptosis, apoptosis-related markers, NLRP3, and ASC levels in the kidney tissues were examined utilizing H&E, Masson, PAS, TUNEL staining, and Western blot. RESULTS: MIC-1 decreased the body weight, kidney weight, the levels of Glu, Scr, and urine albumin in db/db mice. Moreover, MIC-1 significantly suppressed the levels of MDA, insulin, GHb, TNF-α, IL-1ß, and IL-6, while increased the activities of SOD, CAT, and GPX in the serum of db/db mice. MIC-1 also mitigated the kidney tissue injury in db/db mice. Western blot assay showed that MIC-1 enhanced the Bcl-2 level and suppressed the Bax, cleaved caspase-3, cleaved caspase-9, NLRP3, ASC, and caspase-1 levels of the kidney tissues in db/db mice. CONCLUSIONS: MIC-1 ameliorated the kidney injury in DN mice, and its mechanism may be associated with the suppression of renal cell apoptosis, oxidative stress, and inflammatory responses.

Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Although primary UM can be effectively controlled, a significant proportion of cases (40% or more) eventually develop distant metastases, commonly in the liver. Metastatic UM remains a lethal disease with limited treatment options. The initiation of UM is typically attributed to activating mutations in GNAQ or GNA11. The elucidation of the downstream pathways such as PKC/MAPK, PI3K/AKT/mTOR, and Hippo-YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (BAP1) or splicing factor 3b subunit 1 (SF3B1) are considered crucial for the acquisition of malignant potential. Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.

Crocin protects against endoplasmic reticulum stress-related tubular injury in diabetic nephropathy via the activation of the PI3K/AKT/Nrf2 pathway.

Objectives: Diabetic nephropathy (DN) is the main cause of end-stage renal disease, but the current treatment is not satisfactory. Crocin is a major bioactive compound of saffron with antioxidant and anti-endoplasmic reticulum stress (ERS) abilities used to treat diabetes. This study specifically investigated whether crocin has a regulatory role in renal injury in DN. Materials and Methods: The experiment was divided into control, (db/m mice), model (db/db mice), and experimental groups (db/db mice were intraperitoneally injected with 40 mg/kg crocin). Renal function-related indicators (Scr, BUN, FBG, UP, TG, TC, ALT, and AST) and oxidative stress-related indicators (ROS, MDA, GSH, SOD, and CAT) were assessed. The pathological changes of renal tissues were confirmed by HE, Masson, PAS, and TUNEL staining. The levels of ERS-related proteins (GRP78 and CHOP), apoptosis-related proteins, and PI3K/AKT and Nrf2 pathways-related proteins in renal tissue were detected. Results: In db/db mice, renal function-related indicators, apoptotic cells of renal tissues, the contents of ROS and MDA as well as the expressions of CHOP, GRP78, and Bax were increased, the degree of renal tissue damage was aggravated, while the contents of GSH, SOD, and CAT, as well as the protein levels of Nrf2, PARP, anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xl) were decreased compared to the db/m mice. However, crocin treatment reversed the above-mentioned situation. The expressions of the PI3K/AKT and Nrf2 pathways-related proteins were also activated by crocin. Conclusion: Crocin inhibited oxidative stress and ERS-induced kidney injury in db/db mice by activating the PI3K/AKT and Nrf2 pathways.

Inflammatory suppression and immunity regulation benefits of honokiol in a rat model of acute peritonitis via the regulation of NLRP3 inflammasome and Sirt1/autophagy axis.

BACKGROUND: NLRP3 inflammasome and Sirt1/autophagy axis are potential targets for advancing acute peritonitis (AP). Honokiol (HNK), a bioactive substance, has the potential to improve AP. MATERIALS AND METHODS: The AP model rats were established by cecal ligation and puncture (CLP). Rats were randomized into the Sham, Sham+HNK, CLP, and CLP+HNK groups. The therapeutic effects of HNK on organ infection, inflammation and immunity were observed in AP rats. The inflammation of RAW 264.7 cells was induced by lipopolysaccharide (LPS) and divided into the Control, HNK, LPS, and LPS+HNK groups. The effects of HNK on immunity and inflammation were observed. Moreover, the inflammatory cell model was further transfected with NLRP3 overexpressing plasmid, and the regulatory effect of HNK on NLRP3 in AP cells was detected. RESULTS: HNK treatment improved survival, biochemical indexes, and lung and kidney injury and inhibited inflammatory cytokine release and bacterial infection in CLP rats. In CLP rats and RAW 264.7 cells, HNK treatment improved the release of the CD4+ and CD8+ T cells, decreased the associated proteins' levels of the NLRP3 inflammasome, and activated the expression of proteins in the Sirt1/autophagy axis. It improved viability and reduced apoptosis and the degrees of TNF-α, IL-1ß, and IL-6 mRNA in RAW 264.7 cells. In addition, HNK treatment antagonized the effect of NLRP3-overexpressed on inflammation and immunity. CONCLUSIONS: HNK improved AP by inhibiting NLRP3 inflammasome and activating the Sirt1 autophagy axis in vivo and in vitro.

Potential protective effects of the water-soluble Chinese propolis on experimental ulcerative colitis.

OBJECTIVE: To investigate the outcome of Chinese water-soluble propolis (WSP) on the inflammatory response and oxidative stress (OS) of colonic mucosa in rats with ulcerative colitis. METHODS: Dextran sulfate sodium (DSS) was employed to establish the ucerative colitis (UC) rat model. Forty-eight male rats were arbitrarily separated into six groups, namely control, UC, low-dose water-soluble propolis (L-WSP), medium-dose water-soluble propolis (M-WSP), high-dose water-soluble propolis (H-WSP), and sulfasalazine (Sulfa). In this study, we adopted a method of pre-administration and reconstruction of the model that assessed the water-soluble propolis mediated protection against DSS-induced UC rats. Moreover, we examined the body weight (BW), disease activity index (DAI), bloody stool, colon length, and intestinal mucosal injury index of rats. In addition, using enzyme linked immunosorbent assays, we assessed indicators, such as, colonic myeloperoxidase (MPO), interleukin-6 (IL-6), interleukin-9 (IL-9), tumor necrosis factor-ɑ (TNF-ɑ), superoxide dismutase (SOD), malondialdehyde, and glutathione peroxidase (GSH-Px) levels. RESULTS: The pro-inflammatory cytokine expression, as well as OS, was increased in the model rats. However, upon WSP intervention, both pro-inflammatory cytokine levels and OS reduced dramatically, and the therapeutic effect was dose-dependent. CONCLUSION: WSP downregulates OS by enhancing the function of endogenous antioxidant enzymes like SOD and GSH-Px, that inhibit neutrophil activity, as well as diminish pro-inflammatory cytokines like TNF-ɑ, IL-6, and IL-9, along with mechanisms that attenuate intestinal inflammation in UC rat model.

Diosmin mitigates high glucose-induced endoplasmic reticulum stress through PI3K/AKT pathway in HK-2 cells.

BACKGROUND: Diosmin has been reported to treat diabetes, but its role in diabetic nephropathy (DN) remains unclear. This research investigated the mechanism by which diosmin alleviated high glucose (HG)-induced HK-2 cell injury. METHODS: First, we used CCK-8 to detect the effect of 0.1, 1, or 10 µg/mL diosmin on the viability of HK-2 cells treated with normal glucose or HG. Next, we used flow cytometry, automatic biochemical analyzer, ELISA, immunofluorescence, and colorimetric assay kit to examine the apoptosis, oxidative stress, inflammatory factors, and Caspase-3 expression in HK-2 cells. Thereafter, we used the western blot and qRT-PCR to examine the expression of the endoplasmic reticulum stress-, oxidative stress-, inflammation-, apoptosis-, and autophagy, and PI3K/AKT pathway-related factors. RESULTS: Diosmin was non-cytotoxic to normal HK-2 cells and enhanced the HK-2 cell viability suppressed by HG. Meanwhile, diosmin restrained apoptosis, the contents of MDA, pro-inflammatory factors, and Caspase-3 but intensified the contents of SOD and CAT induced by HG. We further confirmed that diosmin blunted oxidative stress-, inflammation-, apoptosis-, and autophagy-related factors expression induced by HG via restraining the CHOP and GRP78 expressions. Further, we also discovered that PTEN level was restrained and the ratios of p-PI3K/PI3K and p-AKT/AKT were enhanced in HK-2 cells induced by HG, which was reversed by co-treatment of HG and diosmin. CONCLUSIONS: Our study manifested that diosmin alleviated the HG-mediated endoplasmic reticulum stress injury in HK-2 cells via restraining the PI3K/AKT pathway.

Development of a method to screen and isolate xanthine oxidase inhibitors from black bean in a single step: Hyphenation of semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography.

Black bean, in which isoflavones are the main active constituent, also contains saponins and monoterpenes. Soybean isoflavone is a secondary metabolite that is formed during the growth of soybean; it exhibits antioxidant and cardiovascular activities and traces estrogen-like effects. In this study, black bean isoflavones were extracted with n-butanol, and ultrafiltration-liquid chromatography-mass spectrometry was used to screen their activity. Subsequently, the inhibitors were isolated and purified using semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography. Thereafter, five active compounds were identified using mass spectrometry and nuclear magnetic resonance experiments. Finally, the inhibition types of the xanthine oxidase inhibitors were determined using enzymatic kinetic studies. The IC50 values of daidzin, glycitein-7-O-glucoside, genistin, daidzein, and genistein were determined to be 35.08, 56.22, 30.76, 68.79, and 95.37 µg/mL, respectively. Daidzin, genistin, and daidzein exhibited reversible inhibition, whereas glycitein-7-O-glucoside and genistein presented irreversible inhibition. This novel approach, which was based on ultrafiltration-liquid chromatography-mass spectrometry and stepwise flow rate countercurrent chromatography, is a powerful method for screening and isolating xanthine oxidase inhibitors from complex matrices. The study of enzyme inhibition types is helpful for understanding the underlying inhibition mechanism. Therefore, a beneficial platform was developed for the large-scale production of bioactive and nutraceutical ingredients.

Complete mitochondrial genome of the mulberry psyllid Paurocephala sauteri Enderlein (Hemiptera: Psyllidae) and phylogenetic analysis.

Paurocephala sauteri (Enderlein, 1914) (Hemiptera: Psyllidae) is a species of a psyllid distributed in Asia. Mulberry is the only known host for P. sauteri until now. The complete mitogenome of P. sauteri (accession number: MT759765) 14,963 bp in size, including 13 protein-coding genes, 22 transfer RNAs, and two ribosomal RNAs genes. The base composition of the whole P. sauteri mitogenome is 40.26% for A, 7.86% for G, 34.07% for T, and 11.81% for C, with a high AT bias of 80.33%. The mitochondrial genome of P. sauteri was sequenced and annotated as the first representative of family Paurocephalidae. The present data could contribute to a detailed phylogeographic analysis of this valuable economic insect for further study in differentiating closely related species.

High alkaline phosphatase and low intact parathyroid hormone associate with worse clinical outcome in peritoneal dialysis patients.

OBJECTIVE: Alkaline phosphatase (ALP) is used as a biomarker to monitor the chronic kidney disease-mineral bone disorder (CKD-MBD) and high levels of parathyroid hormone (PTH) that were reported to be related to increased mortality in CKD patients. Therefore, we conducted this longitudinal cohort study to evaluate the relations between ALP and intact PTH (iPTH) and the associations with all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients. METHODS: In 1276 incident PD patients (median age 50 years, 56% males), baseline serum ALP, iPTH, and metabolic biomarkers potentially linked to CKD-MBD were analyzed in relation to mortality during follow-up period of up to 60 months. All-cause and cardiovascular mortality risk of ALP and iPTH were analyzed with competing-risks regression models with transplantation as competing risk adjusting for all covariates. RESULTS: After adjustments for confounders by logistic regression model, older age, higher change level to levels of iPTH, S-albumin, calcium, alanine transaminase (ALT), and lower level of phosphorus were associated with higher ALP level (>79 U/L), and female gender, non-diabetes mellitus, younger age, lower calcium, higher ALT, total bilirubin, phosphorus, and ALP were associated with higher iPTH level (>300 pg/mL). During 60 months (median 44 months) of follow-up, the all-cause mortality rate was 16%, and 91 (46%) of the 199 deaths were caused by cardiovascular disease. In competing-risks regression analysis, "high ALP + low iPTH" was independently associated with all-cause and cardiovascular mortality after adjustment for age, gender, presence of diabetes, and cardiovascular disease, the calendar year of recruitment and vitamin D therapy in PD patients. The subhazard ratio (sHR) of group "high ALP + low iPTH" was 1.96 times and 3.35 times higher than sHR of group "low ALP + high iPTH" for all-cause mortality and cardiovascular mortality, respectively. CONCLUSIONS: The combination of high ALP and low iPTH was independently associated with increased all-cause and cardiovascular mortality in PD patients, suggesting that ALP and iPTH have the potential to predict clinical outcomes and might be useful risk assessment tools in PD patients. Further studies exploring the observed association between combination of ALP with iPTH and mortality are warranted.

Spin-Momentum-Locked Edge Mode for Topological Vortex Lasing.

Spin-momentum locking is a direct consequence of bulk topological order and provides a basic concept to control a carrier's spin and charge flow for new exotic phenomena in condensed matter physics. However, up to date the research on spin-momentum locking solely focuses on its in-plane transport properties. Here, we report an emerging out-of-plane radiation feature of spin-momentum locking in a non-Hermitian topological photonic system and demonstrate a high performance topological vortex laser based on it. We find that the gain saturation effect lifts the degeneracy of the paired counterpropagating spin-momentum-locked edge modes enabling lasing from a single topological edge mode. The near-field spin and orbital angular momentum of the topological edge mode lasing has a one-to-one far-field radiation correspondence. The methodology of probing the near-field topology feature by far-field lasing emission can be used to study other exotic phenomena. The device can lead to applications in superresolution imaging, optical tweezers, free-space optical sensing, and communication.

Stable, high-performance sodium-based plasmonic devices in the near infrared.

Plasmonics enables the manipulation of light beyond the optical diffraction limit1-4 and may therefore confer advantages in applications such as photonic devices5-7, optical cloaking8,9, biochemical sensing10,11 and super-resolution imaging12,13. However, the essential field-confinement capability of plasmonic devices is always accompanied by a parasitic Ohmic loss, which severely reduces their performance. Therefore, plasmonic materials (those with collective oscillations of electrons) with a lower loss than noble metals have long been sought14-16. Here we present stable sodium-based plasmonic devices with state-of-the-art performance at near-infrared wavelengths. We fabricated high-quality sodium films with electron relaxation times as long as 0.42 picoseconds using a thermo-assisted spin-coating process. A direct-waveguide experiment shows that the propagation length of surface plasmon polaritons supported at the sodium-quartz interface can reach 200 micrometres at near-infrared wavelengths. We further demonstrate a room-temperature sodium-based plasmonic nanolaser with a lasing threshold of 140 kilowatts per square centimetre, lower than values previously reported for plasmonic nanolasers at near-infrared wavelengths. These sodium-based plasmonic devices show stable performance under ambient conditions over a period of several months after packaging with epoxy. These results indicate that the performance of plasmonic devices can be greatly improved beyond that of devices using noble metals, with implications for applications in plasmonics, nanophotonics and metamaterials.

[Effects of Human Amniotic Mesenchymal Stem Cells on Acute Graft-Versus-Host Disease in Xenotransplantation].

OBJECTIVE: To investigate the effects of human amniotic mesenchymal stem cell（AMSC） on acute graft-versus-host disease (aGVHD) in xenotransplatation. METHODS: NPG mice were injected with human PBMNC via tail vein to establish a xenografted aGVHD model. The mice in the experimental group were divided into PBMNC infusion group and PBMNC+AMSC co-infusion group, the general condition, survival time and manifestations of aGVHD were observed, the body weight and blood routine indicators were detected, the pathological changes of aGVHD target organs (lung, liver, spleen, small intestine) were observed by HE staining, and the levels of human T cells in peripheral blood, tissues and organs of mice was detected by flow cytometry. RESULTS: The manifestations of aGVHD (lassitude hunchback, shrub, weight reduction, etc.) and the pathological damage of the target organs (lung, liver, spleen, intestine) in PBMNC+AMSC co-infusion group were lighter than those in PBMNC infusion group. Moreover, the PBMNC and AMSC co-infusion significantly reduced the implantion proportion of human T lymphocytes (CD3+, CD45+) in mice and increased the ratio of CD4+/CD8+. CONCLUSION: Infusion of human-derived AMSC can attenuate the manifestations of aGVHD in mouse xenografts to a certain level, and improve the pathological damage of receptor target organs.

The Clinicopathologic Characteristics and Complement Activation of Antineutrophil Cytoplasmic Antibody-associated Vasculitides With Glomerular IgA Deposition.

The renal injury caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are characterized by few or no immune deposits in glomerulus. A growing number of AAV patients with glomerular immunoglobulin (Ig)A deposits have been reported. We retrospectively investigated all AAV patients with glomerular IgA deposits diagnosed in our center. Serum galactose-deficient IgA1 (Gd-IgA1) level and glomerular Gd-IgA1 and IgA staining were measured. Moreover, we detected complement pathway components in their sera. A total of 168 AAV patients were enrolled, including 26 patients with glomerular IgA deposition and 142 patients with pauci-immune-complex deposition. The AAV patients with IgA deposition had a tendency of lower systemic disease activity, presenting with lower erythrocyte sedimentation rate, lower myeloperoxidase-ANCA, and tendency of lower C reactive protein and Birmingham Vasculitis Activity Score. For renal injury, there were no significant differences in clinical data, pathologic parameters, or renal outcome between groups. The serum level of Gd-IgA1 and intensity of glomerular Gd-IgA1 staining in IgA deposition AAV patients were similar to IgA nephropathy patients. All patients in the IgA nephropathy group and AAV groups with or without IgA deposition had the activation of the alternative complement pathway, whereas AAV patients with IgA deposition also had the activation of the classic complement pathway. Correlation analysis showed serum C1q level correlated directly with serum globulin and IgA levels. In conclusion, AAV patients with IgA deposition had the basis of IgA nephropathy and may present lower systemic disease activity. But it differs from pauci-immune AAV or IgA nephropathy by the possible activation of the classic complement pathway.

A high-performance topological bulk laser based on band-inversion-induced reflection.

Topological insulators are materials that behave as insulators in the bulk and as conductors at the edge or surface due to the particular configuration of their bulk band dispersion. However, up to date possible practical applications of this band topology on materials' bulk properties have remained abstract. Here, we propose and experimentally demonstrate a topological bulk laser. We pattern semiconductor nanodisk arrays to form a photonic crystal cavity showing topological band inversion between its interior and cladding area. In-plane light waves are reflected at topological edges forming an effective cavity feedback for lasing. This band-inversion-induced reflection mechanism induces single-mode lasing with directional vertical emission. Our topological bulk laser works at room temperature and reaches the practical requirements in terms of cavity size, threshold, linewidth, side-mode suppression ratio and directionality for most practical applications according to Institute of Electrical and Electronics Engineers and other industry standards. We believe this bulk topological effect will have applications in near-field spectroscopy, solid-state lighting, free-space optical sensing and communication.

[Roles of transforming growth factor - ß1 and heat shock protein 47 in progression of Schistosoma japonicum-induced hepatic fibrosis].

OBJECTIVE: To investigate the dynamic expression of transforming growth factor-ß1 (TGF-ß1) and heat shock protein 47 (HSP47) and explore their roles in the progression of hepatic fibrosis induced by Schistosoma japonicum infection. METHODS: Fifty female mice of the ICR strain were randomly divided into the infection group and the normal control group, of 25 mice in each group. Each mouse in the infection group was infected with 20 ± 1 cercariae of S. japonicum via the abdominal skin, while uninfected animals served as normal control. Five mice were sacrificed 4, 6, 8, 10 and 12 weeks post-infection and liver tissues were sampled. Serum HSP47 and TGF-ß1 was determined using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of liver specimens were observed with hematoxylin & eosin (HE) staining. In addition, the synthesis of alpha 1 chain of type I collagen (COL1A1) was measured using Masson staining, and the mRNA expression of TGF-ß1, HSP47 and COL1A1 was determined using real-time fluorescent quantitative PCR (qPCR) assay. RESULTS: During the period of S. japonicum-induced hepatic fibrosis, the serum HSP47 and TGF-ß1 levels and the mRNA expression of TGF - ß1, HSP47 and COL1A1 gradually increased with the progression of hepatic fibrosis. The serum levels of HSP47 and TGF-ß1 were (179.26 ± 29.87) pg/mL and (22.37 ± 5.21) ng/mL 6 weeks post-infection, respectively, which were significantly greater than those [(150.29 ± 34.91) pg/mL and (18.54 ± 7.78) ng/mL, respectively] in the normal control group (both P values < 0.05). In addition, the mRNA expression of HSP47, COL1A1 and TGF-ß1 was (0.86 ± 0.04), (1.17 ± 0.06) and (0.64 ± 0.13) in mouse liver specimens, which was significantly higher than that (0.23 ± 0.03, 0.20 ± 0.02 and 0.38 ± 0.02) in the normal control group (all P values < 0.01). CONCLUSIONS: The expression of TGF-ß1 and HSP47 during the period of S. japonicum-induced hepatic fibrosis is consistent with the progression of the hepatic fibrosis, and exhibits the same tendency with type I collagen expression. HSP47 is a novel promising diagnosis marker and therapeutic target for S. japonicum-induced hepatic fibrosis.

[Analysis of endemic situation of schistosomiasis based on geographic information system (GIS) in Wuhan City in 2017].

OBJECTIVE: To analyze the endemic sitaution of schistosomiasis based on geographic information system (GIS) in Wuhan City in 2017, so as to provide the reference for further schistosomiasis control activities. METHODS: According to the data of the annual report on the prevention and control of schistosomiasis in Wuhan City in 2017, the spatial database regarding the endemic situation of schistosomiasis was established and analyzed by ArcMap 10.2. RESULTS: The 593 schistosomiasis-endemic villages in Wuhan City were mainly located in the Yangtze River and its major tributaries. Kernel density analysis showed that the endemic villages of three regions with the highest density was located in the west of Caidian District (Zhuru Street), the east of Hannan District (Shamao Street) and the southwest corner of Xinzhou District (Yangluo Street). The sero-positive population was densely distributed in the West of Caidian District (Zhuru Street), which accounted for 34.23% of all seruo-positives in the city. There were 492 farming cattle fenced in Donggan Village in Hongbei Street of Caidian District. A higher density of the area with Oncomelania hupensis snails was located in the southwest region of Caidian District (Xiaosi Street), accounting for 31.22% of the total area with snails. In 2017, the re-emerging area with snails was 36.60 hm2. The high kernel density region with snails was located in Zhuru Street of Caidian District. The region with high density of living snails was located in the central region of Hannan District (Hongbei Production Brigade), the average density of living snails was 0.36 snails/0.1 m2. CONCLUSIONS: The endemic situation of schistosomiasis is at a low level in Wuhan City, and the spatial distribution is not uniform. In some local areas, the historical endemic situation of schistosomiasis is serious and the high risk factors are more concentrated. It is necessary to strengthen the surveillance of schistosomiasis.

Serum Alkaline Phosphatase Predicts Poor Disease-Free Survival in Patients Receiving Radical Gastrectomy.

BACKGROUND Serum alkaline phosphatase (ALP) has been proved to be a negative prognostic factor for several malignancies, but its clinical significance in gastric cancer (GC) patients has not been sufficiently studied. In the present retrospective study, we investigated the effect of serum ALP on disease-free survival (DFS) after radical gastrectomy. MATERIAL AND METHODS We included 491 GC patients receiving radical gastrectomy at the Chinese People's Liberation Army 309th Hospital. Univariate and multivariate analyses were performed to determine factors influencing serum ALP and DFS. The changes in serum ALP and its clinical relevance were also analyzed using the log-rank test and Cox proportional hazards model. RESULTS There were 491 patients who met our inclusion and exclusion criteria. Pre-treatment serum ALP was elevated in 87 of these patients and was normal in the other 404 patients. Elevation of pre-treatment serum ALP was correlated with the tumor diameter (OR=2.642, P=0.017), TNM stage (OR=4.592, P=0.005), and T classification (OR=1.746, P=0.043). DFS was significantly different between patients with normal or elevated pre-treatment serum ALP (median 42.1 vs. 32.8 months, P=0.001) and multivariate analysis suggested pre-treatment serum ALP is an independent risk factor for poor DFS after radical gastrectomy (HR=2.035, P=0.021). In addition, removal of the primary tumor lesion led to an obvious decline in serum ALP activity (median 262 U/L vs. 152 U/L, P<0.001), and monitoring changes in serum ALP can help evaluate the risk of tumor relapse in GC patients (χ²=17.814, P<0.001). CONCLUSIONS Serum ALP is a good predictor of GC patient DFS after radical gastrectomy, and patients with elevated serum ALP have shorter relapse times.

[Advances in the regulatory roles of exosomes on pathological process of schistosomiasis hepatic fibrosis].

Exosomes are a group of membraneous vesicles generated and released by multi-vesicular bodies or cell membranes in a variety of cell types. Acting as important messages between cells, they participate in almost every physiological and pathological process of living organisms. Exosomes contain specific proteins, mRNA, miRNAs, etc. and mediate intercellular communications, signal transductions and gene expressions effectively. Exosomes are involved in the formation of hepatic fibrosis, which is the typical liver pathological change in the progression of schistosomiasis and is caused by the liver repair and (or) regeneration involving inflammation stimulated by exosomes, activated hepatic stellate cells and other related pathways in reaction to the parasite infection. Exosomes could serve as new markers for schistosomiasis hepatic fibrosis diagnosis and potential targets for its treatment. This paper briefly reviews the latest development of studies on the regulatory roles of exosomes in schistosomiasis hepatic fibrosis, so as to provide ideas for searching new treatment targets of the disease.

[Effect of GnRHa controlled ovarian hyperstimulation on mouse embryo implantation and its mechanism].

The purpose of the present study was to investigate the effects and underlying mechanism of gonadotropin-releasing hormone agonist (GnRHa) controlled ovarian hyperstimulation (COH) on embryo implantation in mice. Forty female Kunming mice aged 9 weeks were randomly divided into two groups (control and COH groups). The COH group received intraperitoneal (i.p.) injections of aminocyclin acetate (GnRHa), human menopausal gonadotropin (HMG) and human chorionic gonadotropin (hCG), while the control group was given equal amount of physiological saline by i.p. injection. One male mouse and two female mice were put into the same cage at 16:00 on the hCG injection day, and on the fourth day of pregnancy, 10 mice from each group were killed. The levels of serum estradiol (E2) and progesterone (P) were measured by radioimmunoassay; HE staining was used to observe the morphology of ovarian and endometrial tissues. The protein expression levels of endometrial leukemia inhibitory factor (LIF), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), heparin-binding epidermal growth factor-like growth factor (HB-EGF) and glycodelin A were detected by Western blot and immunohistochemistry. Ten mice from each group were sacrificed on the eighth day of pregnancy, and the status of the uterus and the average number of blastocysts were observed. The results showed that, compared with control group, the serum E2 level in COH group was significantly decreased (P < 0.05), while the P level was increased significantly (P < 0.05); the ovarian follicles at different developmental stages were rare, corpus lutea (CL) were visible and multiple, the endometrium was thinned, and the number of endometrial glands was reduced (P < 0.05); the contents of LIF, p-STAT3, HB-EGF and glycodelin A in the endometrium were decreased significantly (P < 0.05) on the fourth day of pregnancy; mouse blastocysts developed slowly and were decreased in number on the eighth day of pregnancy (P < 0.05). The above results suggest that GnRHa COH can affect embryo implantation in mice. The mechanism may be related to the imbalance of gonadal hormone, the changes in the structure of the endometrium and the expressions of LIF, p-STAT3, HB-EGF and glycodelin A in the implantation stage, which may lead to the decrease of endometrial receptivity and the abnormal dialogue between the embryo and the uterus.