In this review, we summarize the involvement of vitamin C in mental disorders by presenting available evidence on its pharmacological effects in animal models as well as in clinical studies. Vitamin C, especially its reduced form, has gained interest for its multiple functions in various tissues and organs, including central nervous system (CNS). Vitamin C protects the neuron against oxidative stress, alleviates inflammation, regulates the neurotransmission, affects neuronal development and controls epigenetic function. All of these processes are closely associated with psychopathology. In the past few decades, scientists have revealed that the deficiency of vitamin C may lead to motor deficit, cognitive impairment and aberrant behaviors, whereas supplement of vitamin C has a potential preventive and therapeutic effect on mental illness, such as major depressive disorder (MDD), schizophrenia, anxiety and Alzheimer's disease (AD). Although several studies support a possible role of vitamin C against mental disorders, more researches are essential to accelerate the knowledge and investigate the mechanism in this field.

Kinsenoside is a main active component isolated from plants of the genus Anoectochilus, and exhibits many biological activities and pharmacological effects, including hepatoprotective, anti-hyperglycemic, anti-hyperliposis, anti-inflammatory, vascular protective and anti-osteoporosis effects and so on, which is contributing to its promising potency in disease treatments. This review aims to recapitulate the pharmacological functions of kinsenoside, as well as its source, extraction, identification, quantitative analysis, pharmacokinetics, synthesis and patent information. The data reported in this work can confirm the therapeutic potential of kinsenoside and provide useful information for further new drug development.

Cancer testis antigens (CTAs) are attractive targets for tumor immunotherapy because of their tumor-specific expression. Since more than half of confirmed CTAs are located on the X-chromosome, we asked whether there is a link between CTA expression and X-chromosomes. Recent reports have shown that reactivation of the inactive X-chromosome, known as X-chromosome reactivation (XCR), a unique phenomenon that exists in many high-risk tumors in women, can transform the expression of many X-linked genes from monoallelic to biallelic. In this review, we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.

Hepatitis B virus X (HBx) protein plays a pivotal role in the development of hepatitis B virus (HBV)-associated hepatocellular carcinoma. Although regulation of cytosolic calcium is essential for HBV replication and is mediated by HBx protein, the mechanism of HBx protein regulating intracellular calcium level remains poorly understood. The present study examined whether HBx protein elevated the intracellular calcium through interacting with storeoperated calcium entry (SOCE) components, Orail and stromal interaction molecule 1, and then identified the targets of HBx protein, with an attempt to understand the mechanism of HBx protein upsetting intracellular calcium homeostasis. By employing co-immunoprecipitation and GST-pull-down assay, we found that Orail protein interacted with HBx protein, and the C-terminus of Orail was implicated in the interaction. Confocal microscopy also revealed that HBx protein could co-localize with full-length Orail protein in HEK293 cells. Moreover, live cell calcium imaging exhibited that HBx protein elevated intracellular calcium, possibly by binding to SOCE components. Our results suggest that HBx protein binds to STIM1-Orail complexes to positively regulate the activity of plasma membrane store-operated calcium channels.

Low-dose cytarabine combined with differentiating or DNA hypomethylating agents, such as vitamin D compounds, is a potential regimen to treat acute myeloid leukemia (AML) patients who are unfit for high-intensity chemotherapy. The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3 (1,25-D3). Here, firstly, cBioPortal database was used and we found out that vitamin D receptor (VDR) was highly expressed in acute monocytic leukemia (M5) and high VDR expression was associated with a poor survival of AML patients. Then, we confirmed that 1,25-D3 at clinical available concentration could induce more significant differentiation in acute monocytic leukemia cell lines (U937, MOLM-13, THP-1) and blasts from M5 patients than in non-monocytic cell lines (KGla and K562) and blasts from M2 patient. Finally, it was shown that the combination of 1,25-D3 and low-dose cytarabine further increased the differentiating rate, growth inhibition and G0/G1 arrest, while mild changes were found in the apoptosis in acute monocytic leukemia cell lines. Our study demonstrates that the enhanced response of acute monocytic leukemia cells to low-dose cytarabine by 1,25-D3 might indicate a novel therapeutic direction for patients with acute monocytic leukemia, especially for elderly and frail ones.

Bortezomib, the first potent therapeutic proteasome inhibitor, has been suggested as a standard care in patients with newly diagnosed and relapsed multiple myeloma (MM). However, evidence bearing on the efficacy and safety of subcutaneous (SC) versus intravenous (IV) administration of bortezomib for MM patients is controversial. Randomised controlled trials (RCTs) and observational studies were enrolled in our meta-analysis to investigate the efficacy and safety of bortezomib via SC vs. IV administration on MM patients. Sixteen trials with a total of2575 patients with MM (SC, n=1191; IV, n=1384) were included in our meta-analysis. There were no significant differences between these two arms regarding overall response rate (ORR), complete response (CR), or very good partial response (VGPR). The pooled RRs for rate of adverse events (AEs), such as thrombocytopenia and bortezomib-induced peripheral neuropathy (BIPN), were 0.79 (95% CI: 0.68-0.92) and 0.63 (95% CI: 0.51-0.79), respectively. Moreover, there was much more largely decreased incidence of grade 3 and higher thrombocytopenia and BIPN in bortezomib SC administration than IV route. In general, alternative SC administration should be considered instead of IV administration in use of bortezomib for patients with MM. Key words: bortezomib; multiple myeloma; meta-analysis; subcutaneous administration

In this study, we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine (HAM) with that of high-dose cytarabine alone (HiDAC) as consolidation regimens in non-acute promyelocytic leukemia (APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics. A total of 62 patients from Shenzhen People's Hospital were enrolled in this study. All patients enrolled received standard induction chemotherapy and achieved the first complete remission (CR1). In these patients, 24 received HiDAC and 38 received HAM as consolidation. The median relapse free survival (RFS) and overall survival (OS) were similar between these two consolidation regimens. Even in subgroup analysis according to risk stratification, the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics. However, in patients receiving HAM regimen, the lowest neutrophil count was lower, neutropenic period longer, neutropenic fever rate higher, and more platelet transfusion support was required. HAM group also tended to have higher rate of sepsis than HiDAC group. According to our results, we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to HiDAC, even in young non-APL AML patients with favorable and intermediate cytogenetics.

Regulatory T cells (Tregs) play a pivotal role in the pathological development of hypertension. Helios, a transcription factor from the Ikaros family, was recently reported to be a bona fide marker for natural Tregs or activated Tregs with suppression function, however, little has been known about its role in hypertension. This study was aimed to find whether Helios+ Tregs really play a vital role in hypertension. A total of 60 hypertension patients, and 46 normotension subjects were enrolled in this study. Frequencies of different Tregs subsets in peripheral blood were measured by flow cytometry. Plasma cytokine level was determined by ELISA. The mRNA expression of Foxp3 and Helios in purified CD4+ T cells was detected by RT-PCR. Proportion of CD4+Foxp3+Helios+ Tregs was decreased significantly in patients with hypertension (62.52%±1.18% vs. 71.89%±1.03%, P<0.01), and it was correlated with plasma level of IL-10 positively (a=0.505, P<0.05) and plasma level of IFN-gamma negatively (r=—0.551, P<0.05). The mRNA expression of Foxp3 (7.23±1.00 vs. 10.58±0.54, P<0.05) and Helios (8.47±0.95 vs. 15.52±2.0, P<0.05) was decreased in CD4+ T cells from patients with hypertension. Helios+ Tregs were decreased in patients with hypertension and may play a protective role in hypertension progression.

Physical inactivity is very common in octogenarians. However, association between physical inactivity and mortality in octogenarians with acute coronary syndrome (ACS) remains unclear. In this study, we aimed to investigate association between physical inactivity and allcause mortality in octogenarian patients with ACS. In this study, we included a total of 353 hospitalized patients, aged >80 years, with ACS during the period of 5-year follow-up. The association between physical inactivity and all-cause mortality was analyzed by multivariable Cox aggression. Of the enrolled patients, 132 (37.4%) were defined as physically inactive, and 221 (62.6%) as physically active. Patients with physical inactivity tended to have lower survival rate (21.2% vs. 56.5%, P<0.001) and higher mortality rate (78.8% vs. 43.5%, PcO.OOl), and had a worse long-term outcome than those with physical activity (chi-square=27.52, and log rank PcO.OOl). The physical inactivity was still an independent predictor for long-term allcause mortality independent of confounders including age, prior heart failure, stroke, ejection fraction, beta-blocker, clopidogrel and percutaneous coronary intervention (HR: 2.35, 95% CI: 1.26-4.37, P=0.007). Our study demonstrates that physical inactivity is independently related to increased all-cause mortality in octogenarians with ACS.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which could induce the poor prognosis. The purpose of this study was to characterize the molecular mechanism of the functional changes of CDllb+/Ly6C^intermediate macrophages after renal IRI. The gene expression profiles of CDllb+/Ly6Cintermcdiate macrophages of the sham surgery mice, and the mice 4 h, 24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database. Analysis of mRNA expression profiles was conducted to identify differentially expressed genes (DEGs), biological processes and pathways by the series test of cluster. Protein-protein interaction network was constructed and analysed to discover the key genes. A total of 6738 DEGs were identified and assigned to 20 model profiles. DEGs in profile 13 were one of the predominant expression profiles, which are involved in immune cell chemotaxis and proliferation. Signet analysis showed that Atp5al, Atp5o, Cox4i, Cdc42, Rac2 and Nhp2 were the key genes involved in oxidation-reduction, apoptosis, migration, M1-M2 differentiation, and proliferation of macrophages. RPS18 may be an appreciate reference gene as it was stable in macrophages. The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD 1lb⁺Ly6C^intermediate macrophages after renal IRI. Moreover, the vital gene Nhp2 may involve the polarization of macrophages, which may be a new target to affect the process of AKI

In the present study, we aimed at exploring the applied value of preoperative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in the prediction of lymph node metastasis (LNM) and prognosis in patients with early gastric cancer (EGC). We retrospectively analyzed a total of248 consecutive patients who underwent curative gastrectomy to be identified T1 stage gastric adenocarcinoma between January 1, 2010 and May 1, 2016 in a single institution. According to median preoperative NLR and PLR value, we divided the patients into four groups: high NLR >1.73 and low NLR <1.73, high PLR >117.78 and low PLR <117.78. Furthermore, to evaluate the relationship between preoperative NLR and PLR values, we categorized patients according to cutoff preoperative NLR-PLR score of 2 [high NLR (>1.73) and high PLR (>117.78)], 1 [either high NLR or high PLR], and 0 [neither high NLR nor high PLR], Statistical analyses were conducted using SPSS 20.0 software. The results showed that the preoperative NLR or PLR values, lower or higher, could not predict the LNM in patients with EGC (both P=0.544>0.05). The invasive depth of tumor was significantly correlated with LNM of EGC (P0.001). Kaplan-Meier plots illustrated that preoperative NLR and PLR values were not associated with overall survival (OS) in patients with EGC. It was concluded that the preoperative NLR and PLR may be the predictors for LNM and prognosis in patients with advanced gastric cancer; nevertheless, they cannot predict LNM and prognosis in patients with EGC.

Nitinol alloy occluders are widely used in the transcatheter intervention treatment of congenital heart diseases like patent ductus arteriosus (PDA). However, nitinol alloy contains high levels of nickel, which can lead to toxic effects in the immune and hematopoietic systems if released in sufficient quantities. A new type of single-rivet occluder coated with nano-film has been developed to limit the release of nickel. In total, 23 patients were recruited and randomly assigned to the experimental group (n=12) with the new nano-film single-rivet occluders or the control group (n=11) with the traditional occluders. One case in the control group was lost to follow-up. The remaining 22 cases were followed up at 24 h, 7 days, 1 month, 3 months, and 6 months after the procedure. There were no statistically significant differences in routine blood test, alanine aminotransferase, creatinine, and troponin between the experimental and control groups. Serum nickel concentration in both two groups increased at 24 h after the procedure, peaked at 1 month, and returned to preoperative levels at 6 months. Serum nickel levels in the experimental group were significantly lower than in the control group at 24 h, 7 days, 1 month, and 3 months after the procedure. These data suggested that the nano-film coating effectively prevented nickel release from the new occluders, and therefore has a preferable safety profile.

The aim of the present study is to address the effect of rapamycin on abdominal aortic aneurysm (AAA) and the potential mechanisms. A clinically relevant AAA model was induced in apolipoprotein E-deficient (ApoE-/-) mice, in which miniosmotic pump was implanted subcutaneously to deliver angiotensin II (Ang II) for 14 days. Male ApoE-/- mice were randomly divided into 3 groups: saline infusion, Ang II infusion, and Ang II infusion plus intraperitoneal injection of rapamycin. The diameter of the supra-renal abdominal aorta was measured by ultrasonography at the end of the infusion. Then aortic tissue was excised and examined by Western blotting and histoimmunochemistry. Ang n with or without rapamycin treatment was applied to the cultured vascular smooth muscle cells (VSMCs) in vitro. The results revealed that rapamycin treatment significantly attenuated the incidence of Ang II induced-AAA in ApoE-/- mice. Histologic analysis showed that rapamycin treatment decreased disarray of elastin fibers and VSMCs hyperplasia in the medial layer. Immunochemistry staining and Western blotting documented the increased phospho-ERK1/2 and ERK1/2 expression in aortic walls in Ang II induced-AAA, as well as in human lesions. Whereas in the rapamycintreated group, decreased phospho-ERKl/2 expression level was detected. Moreover, rapamycin reversed Ang II -induced VSMCs phenotypic change both in vivo and in vitro. Based on those results, we confirmed that rapamycin therapy suppressed Ang II -induced AAA formation in mice, partially via VSMCs phenotypic modulation and down-regulation of ERK1/2 activity.

This study is aimed to evaluate the effectiveness and safety of the treatment of highflow priapism with superselective transcatheter embolization. From Sep. 1999 to Jan. 2013, six patients with high-flow priapism underwent superselective transcatheter embolization of the cavernous artery. Recurrence of priapism, and change in erectile function detected by nocturnal penile tumescence and rigidity (NPTR) test and the International Index of Erectile Function 5-item questionnaire (IIEF-5) were evaluated during a mean follow-up of 12 months. A single superselective transcatheter embolization was sufficient for complete resolution of priapism in the six patients. None of the patients had a relapse of priapism after embolization, and all the patients who had premorbid normal erectile function showed maintained potency with normal results of NPTR and a mean postoperative IIEF-5 score of 23.5 (range 23 to 24) during the follow-up period. In conclusion, superselective transcatheter embolization is an effective and safe treatment method for high-flow priapism, and it can ensure a high level of preservation of premorbid erectile function.

Low-temperature plasma (LTP) has shown great promise in wound healing, although the underlying mechanism remains poorly understood. In the present study, an argon atmospheric pressure plasma jet was employed to treat L929 murine fibroblasts cultured in vitro and skin wounds in BALB/c mice. The in vitro analysis revealed that treatment of fibroblasts with LTP for 15 s resulted in a significant increase in cell proliferation, secretion of epidermal growth factor (EGF) and transforming growth factor-βi (TGF-βi), production of intracellular reactive oxygen species (ROS), and the percentage of cells in S phase, protein expression of phosphorylated p65 (P-p65) and cyclinD1, but a noted decrease in the protein expression of inhibitor kappa B (IκB). The in vitro experiments demonstrated that 30-s LTP treatment enhanced the number of fibroblasts and the ability of collagen synthesis, while 50-s treatment led to the opposite outcomes. These results suggested that LTP treatment promotes the fibroblast proliferation in wound healing by inducing the generation of ROS, upregulating the expression of P-p65, downregulating the expression of IκB, and activating the NF-κB signaling pathway and consequently altering cell cycle progression (increased DNA synthesis in S phage).

Protein phosphatase 2A (PP2A) was reported to play an important role in cancer development; however, the relationship between PP2A and cervical cancer development has yet to be fully understood. The present study aimed to explore the role of PP2A in the development of cervical cancer. Serum levels of PP2A were detected by ELISA in 23 patients with cervical cancer and 30 patients with benign cervical lesions. Furthermore, the PP2A activities and the mRNA and protein levels of PP2A were measured in cervical cancer (n=8) and chronic cervicitis (n=10) tissues. The results showed that the serum levels of PP2A were significantly reduced in patients with cervical cancer. Further studies showed that not only the activities of PP2A but also the mRNA and protein levels of PP2A were significantly decreased in cervical cancer tissues. Wound healing and Transwell assays demonstrated that pharmacological and genetic upregulation of PP2A could inhibit the migration of HeLa cells, but the downregulation of PP2A promoted cellular migration. The activation of PP2A also inhibited the remodeling of actin and the activity of mitogen-activated protein kinases (MAPKs) including p-JNK, p-p38 and p-ERK. Meanwhile, the activation of PP2A was found to downregulate MMP-9 levels, which further inhibited the migration and invasion of HeLa cells. In conclusion, our data suggest that the activity and expression of PP2A are significantly reduced in cervical cancer tissues, and the activation of PP2A may inhibit the migration of cervical cancer cells by inhibiting the phosphorylation of p-JNK, p-p38 and the p-ERK/MAPK signaling pathway as well as by downregulating MMP-9, implying that PP2A plays an important role in cervical cancer development.

Preeclampsia (PE) is a pregnancy-specific hypertensive complication, closely related to endothelial dysfunction. Adipose derived stem cells (ADSCs) have the capacity to differentiate into endothelial cells for vascular repair. Therefore, we hypothesized that induced endothelial differentiation of ADSCs might hold great potential for the treatment of PE. In this study, the primary ADSCs and human umbilical vein endothelial cells (HUVECs) were isolated by the collagenase digestion method. The supernatant of HUVECs was collected from the first generation of cells. Then, ADSCs were divided into two groups: ADSCs alone group and induced ADSCs (iADSCs) group. In iADSCs group, ADSCs were induced by HUVECs conditioned medium and ADSCs special culture medium at a ratio of 1:1 over a two-week period. In order to identify the endothelial characteristics of iADSCs, CD31 and CD34 were examined by flow cytometry. The proliferation, migration, invasion and angiogenesis assays were employed to compare the bioactivity of iADSCs and ADSCs. Furthermore, The levels of angiogenic related factors including vascular endothelial growth factor (VEGF) and placenta growth factor (P1GF) were detected by RT-PCR and Western blotting. Results showed conditioned medium from HUVECs promoted ADSCs proliferation, migration, invasion and angiogenesis. In addition, the levels of VEGF and P1GF were significantly enhanced in iADSCs group. This study uncovered the iADSCs application potential in the therapy and intervention of PE.

This study aimed to investigate whether intracytoplasmic sperm injection (ICSI) shows an advantage over in vitro fertilization (IVF) in non-male factor cycles as the number of oocytes retrieved decreases from four to one. We undertook a retrospective analysis of 1305 IVF/ICSI cycles of non-male factor in which four or fewer oocytes were retrieved. Comparisons were made between conventional IVF (CI) and ICSI when one, two, three or four oocyte(s) were retrieved. Primary outcomes including normal fertilization rate, proportion of embryos per obtained oocyte, cycle cancellation rate, implantation rate, clinical pregnancy rate (PR), live birth rate (LBR), cumulative PR and cumulative LBR were evaluated. The results showed that the normal fertilization rate (72.5% vs. 50.0%) and the proportion of embryos per obtained oocyte (72.5% vs. 55.0%) were significantly increased in one oocyte retrieved cycles in ICSI group as compared with CI group. However, the proportion of embryos per obtained oocyte was markedly decreased in ICSI group when three (52.3% vs. 61.3%) or four (56.9% vs. 64.0%) oocytes were retrieved. The implantation rates, clinical PRs, LBRs, cumulative PRs and cumulative LBRs in CI group were comparable to those in ICSI group when one, two, three or four oocyte(s) were retrieved. In conclusion, ICSI doesn't show advantages over IVF in low oocyte yield cycles of non-male factors, even when only one oocyte was retrieved.

The different methods in differentiating biliary atresia (BA) from non-BA-related cholestasis were evaluated in order to provide a practical basis for a rapid, early and accurate differential diagnosis of the diseases. 396 infants with cholestatic jaundice were studied prospectively during the period of May 2007 to June 2011. The liver function in all subjects was tested. All cases underwent abdominal ultrasonography and duodenal fluid examination. Most cases were subjected to hepatobiliary scintigraphy, magnetic resonance cholangiopancreatography (MRCP) and a percutaneous liver biopsy. The diagnosis of BA was finally made by cholangiography or histopathologic examination. The accuracy, sensitivity, specificity and predictive values of these various methods were compared. 178 patients (108 males and 70 females with a mean age of 58±30 days) were diagnosed as having BA. 218 patients (136 males and 82 females with a mean age of 61 ±24 days) were diagnosed as having non-BA etiologies of cholestasis jaundice during the follow-up period in which jaundice faded after treatment with medical therapy. For diagnosis of BA, clinical evaluation, hepatomegaly, stool color, serum gamma-glutamyltranspeptidase (GGT), duodenal juice color, bile acid in duodenal juice, ultrasonography (gallbladder), ultrasonography (griangular cord or strip-apparent hyperechoic foci), hepatobiliary scintigraphy, MRCP, liver biopsy had an accuracy of 76.0%, 51.8%, 84.3%, 70.0%, 92.4%, 98.0%, 90.4%, 67.2%, 85.3%, 83.2% and 96.6%, a sensitivity of 83.1%, 87.6%, 96.1%, 73.7%, 90.4%, 100%, 92.7%, 27.5%, 100%, 89.0% and 97.4%, a specificity of 70.2%, 77.5%, 74.8%, 67.0%, 94.0%, 96.3%, 88.5%, 99.5%, 73.3%, 75.4% and 94.3%, a positive predictive value of 69.0%, 72.6%, 75.7%, 64.6%, 92.5%, 95.7%, 86.8%, 98.0%, 75.4%, 82.6% and 98.0%, and a negative predictive value of 83.6%, 8.5%, 95.9%, 75.7%, 92.3%, 100%, 84.2%, 93.7%, 100%, 84.0% and 92.6%, respectively. It was concluded that all the differential diagnosis methods are useful. The test for duodenal drainage and elements is fast and accurate. It is helpful in the differential diagnosis of BA and non-BA etiologies of cholestasis. It shows good practical value clinically.

Ischemia/reperfusion is known to greatly increase oxidative stress in the penumbra, which results in brain damage. Integrin αvβ3 is selectively up-regulated with ischemic injury to the brain and remains elevated throughout reperfusion. We determined whether or not a new compound biotinylated-LXW7-ceria nanoparticle (CeNP) (bLXW7-CeNP) plays a role in brain protection in the rat model of middle cerebral artery occlusion/reperfusion and shows better effects than CeNPs alone in improving the outcomes of focal oxidative stress and apoptosis more effectively. Male Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h followed by a 24-h reperfusion. Drug treatment was intravenously administered via the caudal vein 1 h after occlusion. Rats were randomly divided into the following 4 groups: bLXW7-CeNP treatment group (0.5 mg/kg); CeNP treatment group (0.5 mg/kg); control saline group; and sham group. Brains were harvested 24 h after reperfusion, and the neurologic deficit scores, infarction volume, blood-brain barrier (BBB) disruption, and the level of oxidative stress and apoptosis were determined. Results showed that the bLXW7-CeNP and CeNP treatments could improve neurologic deficit scores, infarction volume, BBB disruption, and the level of oxidative stress and apoptosis. Compound bLXW7-CeNP treatment exhibited better effects than CeNp treatment and showed remarkable statistical differences in the infarction volume, the degree of BBB breakdown, the apoptosis and oxidative stress, apart from neurologic deficit scores. Thus, we concluded that bLXW7-CeNP protects against acute cerebral ischemia/reperfusion injury. BLXW7, as a ligand of integrin αvβ3, may be able to effectively localize the anti-oxidant CeNPs to the ischemic penumbra region, which may provide more adequate opportunities for CeNPs to exert anti-oxidative stress effects and subsequently reduce apoptosis in acute cerebral ischemia/reperfusion.

In this study, the response of Dectin-1 on macrophages to Fusarium solani (F. solani) and the expression patterns of Dectin-1 in experimentally F. solani-induced keratomycosis were investigated. Peritoneal macrophages isolated after intraperitoneal injection of sodium thioglycollate were co-cultured with laminarin and spores of F. solani for 12 h. The expression levels of Dectin-1 and CARD9 were detected by immunofluorescence and real-time quantitative polymerase chain reaction. A mouse model of fungal keratitis was established by substromal inoculation with spores of F. solani. Corneal lesions and inflammatory responses were observed by slit-lamp and histopathology at 1, 2, 3, 5, and 7 day(s) after infection. Dectin-1 expression was significantly upregulated on macrophages stimulated by spores of F. solani. Dectin-1 was not detected in normal corneas of C57BL/6 mice, but detected in infected corneas from the first day after inoculation, with high mRNA levels observed on days 2 and 3. CARD9, a key transducer of Dectin-1 signaling, was also upregulated in infected corneas. In conclusion, Dectin-1 is an important recognition receptor in F. solani-induced keratitis, but the molecular mechanisms warrant further investigation.

This study aimed to study whether the Sortase A (srtA) gene helps mediate coaggregation and co-adherence between Streptococcus mutans (S. mutans) and other salivary bacteria. S. mutans UA159 and srtA-deficient mutant served as “bait” in classical co-aggregation assays and membrane-based co-adherence assays were used to examine interactions of S. mutans with Fusobacterium nucleatum (F. nucleatum), Streptococcus mitis (S. mitis), Streptococcus gordonii (S. gordonii), Streptococcus sanguis (S. sanguis), Actinomyces naeslundii (A. naeslundii) and Lactobacillus. Co-adherence assays were also performed using unfractionated saliva from healthy individuals. Co-adhering partners of S. mutans were sensitively detected using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Both UA159 and its srtA-deficient mutant bound to F. nucleatum but not to any of the other five salivary bacteria. The srtA-deficient mutant showed lower co-adherence with F.nucleatum. The two S. mutans strains also showed similar co-adherence profiles against unfractionated salivary bacteria, except that UA159 S. mutans but not the srtA-deficient bound to a Neisseria sp. under the same conditions. Deleting srtA reduces the ability of S. mutans to bind to F.nucleatum, but it does not appear to significantly affect the binding profile of S. mutans to bulk salivary bacteria.

Baicalin is one of the main active ingredients of choleretic traditional Chinese medicine drug Radix Scutellariae. The aim of this study was to explore the pharmacokinetic characteristics of baicalin in rats with 17α-ethynylestradiol (EE)-induced intrahepatic cholestasis (IC) based on its choleretic effects. Firstly, rats were subcutaneously injected with EE solution (5 mg/kg, 0.25 mL/100 g) for 5 consecutive days to construct an IC model. Then the bile excretion rate, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bile acid (TBA) and pathological changes of the liver were detected. Secondly, after successfully modeling, the rats were intragastrically given baicalin solution (200 mg/kg) (n=6). Blood samples were collected from the tail vein at different time points after intragastric administration. The protective effects of low- (50 mg/kg), medium- (100 mg/kg) and high-dose (200 mg/kg) baicalin on the liver in IC rats were evaluated. The content of baicalin in plasma was detected by liquid chromatography-mass spectrometry/mass spectrometry and pharmacokinetics parameters were calculated. Pharmacodynamic results showed that low-, medium- and high-dose baicalin all significantly increased the average excretion rate of bile (P<0.05), and significantly decreased serum levels of ALT, AST and ALP and TBA (P<0.05). Meanwhile, HE staining showed that baicalin significantly relieved EE-induced hepatocyte edema and necrosis. Pharmacokinetic results exhibited that the absorption of baicalin in both IC and normal control rats showed bimodal phenomenon. C_max, AU_(0-t) and AUC_(0-∞) of baicalin in IC rats were significantly higher than those of the normal control group (P<0.01). T_1/2 of plasma baicalin in the model group was significantly extended to (11.09±1.84) h, with clearance dropping to 61.78% of that of the normal control group (P<0.01). The above results suggested that baicalin had protective effects on the liver of IC rats, accompanied by significantly increased in vivo exposure, delayed in vivo clearance and markedly alterative pharmacokinetic characteristics. This study provides a theoretical basis for further development of baicalin as a feasible drug for treating IC.

B vitamins are enzyme cofactors that play an important role in energy metabolism. The aim of this study was to elucidate whether B vitamin administration can reduce body weight (BW) gain by improving energy metabolism-related enzyme activities in rats fed on a highfat diet. Fifty rats were randomly assigned to one of the following five groups: control group (C), including rats fed on standard rat chow; four treatment groups (HO, HI, H2, and H3), in which rats were fed on a high-fat diet. Rats in the HI group were treated daily with 100 mg/kg BW thiamine (VB1), 100 mg/kg BW riboflavin (VB2), and 250 mg/kg BW niacin (VPP); rats in the H2 group were treated daily with 100 mg/kg BW pyridoxine (VB6), 100 mg/kg BW cobalamin (VB12), and 5 mg/kg BW folate (FA); and rats in the H3 group were treated daily with all of the B vitamins administered to the HI and H2 groups. After 12 weeks, the BW gains from the initial value were 154.5±58.4 g and 159.1±53.0 g in the HI and C groups, respectively, which were significantly less than the changes in the HO group (285.2±14.8 g, P<0.05). In the HO group, the plasma total cholesterol (CHO) and triglyceride (TG) levels were 1.59±0.30 mmol/L and 1,55±0.40 mmol/L, respectively, which were significantly greater than those in the HI group (1.19±0.18 mmol/L and 0.76±0.34 mmol/L, respectively, P<0.05). The activities of transketolase (TK), glutathione reductase, and Na⁺/K⁺ adenosine triphosphatase were significantly increased in the B vitamin-treated groups and were significantly greater than those in the HO group (P<0.05). Furthermore, the glucose-6-phosphate dehydrogenase, pyruvic acid kinase, and succinate dehydrogenase activities also were increased after treatment with B vitamins. Supplementation with B vitamins could effectively reduce BW gain and plasma levels of lipids by improving energy metabolism-related enzyme activities in rats, thus possibly providing potential benefits to humans.

The aim of the present study was to measure the prevalence of multimorbidity in Bangladesh, India and China, and to assess the relationship between multimorbidity and patient's opinion regarding their involvement in healthcare decision-making and overall satisfaction of healthcare system. Cross-sectional data on 18 696 men and women aged 18 and above were collected from the World Health Survey of World Health Organization (WHO). Outcome variables were subjective rating of (1) healthcare system's ability to involve patients in decision-making, and (2) satisfaction with the way healthcare system runs in the country. Self-reported chronic conditions were used to measure the prevalence of multimorbidity. Out of 9 chronic conditions, back pain, arthritis, and chronic cough appeared to be the most prevalent ones among majority of the participants. About one-third of the participants in China (30.7%) and two-thirds in Bangladesh (66.1%) and India (66.6%) reported having at least one chronic illness. Prevalence of multimorbidity was highest in India (34.3%) followed by Bangladesh (28.8%) and China (14.3%). In Bangladesh, India and China, respectively 70.5%, 41.7%, 61.3% women and 54.5%, 42.8% and 58.8 % men expressed dissatisfaction regarding the way healthcare system runs in their country. In Bangladesh and India, men who were living with multimorbidity were more likely to rate the patient-centeredness as “bad” than those who had no disease illness. This study suggests that the prevalence of multimorbidity was remarkably high especially in Bangladesh and India. Higher likelihood of dissatisfaction about healthcare system among multimorbid patients might be indicative of inadequacy in the provision of care in qualitative and quantitative terms.

This study was designed to evaluate the effects of testosterone supplementation (TS) on body composition in patients with HIV and the side effects of TS. A comprehensive literature search strategy was used to retrieve relevant randomized controlled trials (RCTs) examining the effects of TS on body composition. Atotal of 14 eligible studies were included, enrolling 388 and 349 randomized patients in TS and control groups, respectively. The quality of studies included was assessed, and data on total body weight (BW), lean body mass (LBM), fat mass (FM), serum total testosterone (TT), free testosterone (FT) levels, and adverse events were extracted and analyzed using Review Manager software 5.3. Meta-analysis results showed that TS was associated with a small but significant modification in total BW, serum TT, and FT levels in HIV-infected patients and in patients given various drug administrations. TS also significantly increased LBM in male patients, but no significant difference in LBM was observed between female counterparts treated with TS or not. Conversely, TS relative to placebo did not lead to a significant reduction in FM. No significant difference was observed between the two groups in terms of adverse effects. Our findings suggested that TS may be recommended to improve body composition in patients with HIV-related weight loss. However, owing to the high heterogeneity across included trials, further evaluations using large-scale, multi-center, blinded RCTs are needed.