The prevalence and determinants of drug-resistance-associated mutations in the HIV-1-infected MSM population of Henan Province in China.

To estimate the prevalence of human immunodeficiency virus (HIV) drug resistance (DR) in a population of men who have sex with men (MSM) from Henan Province of China and to identify the DR-associated HIV-1 mutations in these MSM. The HIV-positive status of the MSM subjects in this study was confirmed using ELISA and Western blotting. The MSM subjects were classified into non-treatment group (n = 106) and treatment group (n = 313). CD4(+) T-lymphocyte counts were obtained by flow cytometry, and viral load was measured by branched DNA (bDNA) signal amplification assay. HIV-1 genotypic resistance tests were performed by sequence analysis of the HIV-1 protease and reverse transcriptase genes. In the non-treatment group, 15 patients (14.2 %) displayed DR to non-nucleoside reverse transcriptase inhibitor (NNRTI). In the treatment group, the failure rate of viral suppression was 38.33 % and the DR rate was 33.2 %, which was higher than the rate observed in the non-treatment group (P < 0.05). The incidence of mutations corresponding to NNRTI resistance was significantly higher than the incidence of mutations corresponding to nucleoside reverse transcriptase inhibitor (NRTI) resistance (32.9 % vs. 26.5 %) in the cohort. After antiretroviral therapy (ART), the frequencies of K103N, G190A, Y181C, and V106A mutations were highly elevated. Logistic regression analysis results showed that duration of treatment, poor treatment compliance, drug abuse and homosexual orientation are the major risk factors for DR in this MSM population (all P < 0.05). Our results showed that DR-associated mutations in the HIV-1-infected MSM population increased significantly after ART. Furthermore, duration of treatment, poor treatment compliance, drug abuse and homosexual orientation were identified as the risk factors for DR in the MSM population from Henan Province in China.

[A modulation method to improve the signal-to-noise ratio of internal virtual hyperspectrum of body surface].

Virtual internal hyperspectrum of body surface which can express and properly mix the information of skin's composition and structure was expected to apply in the human disease quick-diagnosis, but the weak detected signal was easily impacted by ambient light and dark current from the instrument, so square wave modulated by chopper disk was proposed to resolve this issue. First, we built the experiment platform, and selected both laser and bromine tungsten lamp as the light source, then compared the virtual hyperspectrum of non-modulated and modulated light on human arm in the environment with artificial interference, and demodulated the modulated signal by FFT method. The experiment result showed that modulation method could effectively eliminate the impact brought by environmental light and dark current and improve the signal to noise ratio (SNR), suggesting a new approach to detect human's weak optical signals.

[Study on detection of changes in tissue structure and composition by using virtual internal hyper-spectrum of body surface].

Purposed to achieve the detection of changes in tissue structure and composition simultaneously by virtual internal hyper-spectrum of body surface (VIHBS), we designed the VIHBS system containing modulated light, translation stage device for data acquisition and spectrometer. In the present study, pork meat as the experimental subject was equally divided into three pieces. One piece was used for a control study, and the others were separately embedded with red filter and injected into highly scattering intralipid to imitate the changes in tissue structure and composition. And then, data acquisition of 17 points started at source fiber was taken at intervals of 0.5 mm. The results showed that modulated light can effectively inhibit the influences of ambient light and dark current created by optoelectronic devices. In addition, VIHBS technology achieved the locating of red filter by visible-light and the rapid screening of changes in tissue composition caused by intralipid with near infrared light. The study suggests that it is much feasible to detect the changes in tissue structure and composition by VIHBS. And it is concluded that further research will be likely to provide a new method to realize the early diagnosis and screening of human skin.

[Related factors of early post-operative prognosis of meningiomas: an analysis of 953 surgical cases].

OBJECTIVE: To study the related factors of early post-operative prognosis of meningiomas. METHODS: The clinical data of 953 patients with meningiomas were recorded and statistically analyzed with χ(2) test of single factor and logistic regression model of multivariate factors. Patient age; tumor size; tumor location; pre-operative complication of patients such as hypertension, diabetes, heart disease and cerebral infarction; the extent of tumor resection; hemorrhagic shock; blood loss or hemorrhagic shock and brain swelling intra-operatively were taken as variables. The prognosis was evaluated by postoperative Karnofsky performance scale. RESULTS: The prognosis was significantly correlated with the patient age, tumor size, tumor location, preoperative cerebral infarction, the extent of tumor resection, blood loss and hemorrhagic shock intra-operatively (P < 0.05). Such factors as tumor size, preoperative cerebral infarction, the extent of tumor resection (Simpson's scale) and intra-operative hemorrhagic shock were independent risk factors of prognosis for meningiomas. Other factors, such as hypertension, diabetes and heart disease, were unrelated with the prognosis of meningiomas (P > 0.05). CONCLUSION: Patient age, tumor location and pre-operative complications of patients maybe affect the early postoperative prognosis of meningiomas. But such factors as tumor size, preoperative cerebral infarction, the extent of tumor resection and intra-operative hemorrhagic shock are independent risk factors for the post-operative prognosis of meningiomas.

[Hyperspectral of the body surface tissues: a new synchronous detection technology of the compositional information and structural information].

The present paper innovatively proposed the technology using hyperspectral to detect the body surface tissues that can achieve the systemic analysis of composition and structure by obtaining the multiple spectrum and image information simultaneously. Besides, by the method of data mining, the relationships between diseases and the data including the spectrum, image or synentropy were established. This technology provided more information for the disease detection clinically which can reflect accurately the physiological, biochemical and pathological status and the variation of the body surface tissues, by which both the cost of the equipment and the operation steps can be reduced.

[Validation of feasibility of virtual hyperspectral technology].

To verify the virtual hyperspectral technology for acquiring the internal composition and structure information, the virtual hyperspectral system, which took apples as the test materials, was built. First, we detected the virtual hyperspectral system of the normal apples and ill apples. Then, the virtual hyperspectral of apple slices and apple slices with a piece of red optical filter embedded was detected. Finally, the reflection spectrum of normal apple, ill apple, apple slice and slice with a piece of red filter embedded was detected. The results showed that virtual hyperspectral, which can gain more information than reflection spectrum, could be used for detecting the variation of internal composition and structure. It is a strong evidence that this technology can be used in human body in the future. Virtual hpyerspectral is a new path applied to detecting the biological information, and it can be used for the multi-information and cross-information detection simultaneously and systematically. More foundation for quick disease check-up in vivo was expected to be provided by this technology.

Salidroside inhibits NLRP3 inflammasome activation and apoptosis in microglia induced by cerebral ischemia/reperfusion injury by inhibiting the TLR4/NF-κB signaling pathway.

BACKGROUND: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an important mediator of neuroinflammatory responses that regulates inflammatory injury following cerebral ischemia and may be a potential target. Salidroside (Sal) has good anti-inflammatory effects; however, it remains unclear whether Sal can regulate NLRP3 inflammasome activation through the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway after cerebral ischemia to alleviate inflammatory injury. METHODS: We established an oxygen-glucose deprivation and reoxygenation (OGD/R) model of BV2 cells and a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. Cell Counting Kit-8 (CCK-8), flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were used to detect the viability and apoptosis of BV2 cells. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of inflammatory factors. 2,3,5-triphenyltetrazolium chloride (TTC) staining and modified Neurological Severity Score (mNSS) were used to detect cerebral infarction volume and neurological deficit in rats. Western blot, immunohistochemistry and immunofluorescence staining were used to detect the protein expression levels. RESULTS: Our results showed that Sal increased viability, inhibited lactate dehydrogenase (LDH) release, and reduced apoptosis in OGD/R-induced BV2 cells. Sal reduced the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-8. Following induction by OGD/R, BV2 cells exhibited NLRP3 inflammasome activation and increased protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, IL-1ß, and IL-18. Protein levels of key TLR4 signaling pathway elements, such as TLR4, myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa B p65 (p-NF-κB p65)/NF-κB p65 were upregulated. Interestingly, it was revealed that Sal could reverse these changes. In addition, TAK242, a specific inhibitor of TLR4, had the same effect as Sal treatment on BV2 cells following induction by OGD/R. In the MCAO/R rat model, Sal was also observed to inhibit NLRP3 inflammasome activation in microglia, reduce cerebral infarction volume, and inhibit apoptosis. CONCLUSIONS: In summary, we found that Sal inhibited NLRP3 inflammasome activation and apoptosis in microglia induced by cerebral ischemia/reperfusion injury by inhibiting the TLR4/NF-κB signaling pathway, thus playing a protective role. Therefore, Sal may be a promising drug for the clinical treatment of ischemic stroke.

[Application of hyperspectral imaging technology to objective diagnosis of TCM syndrome].

Hyperspectral imaging technology is expected as a breakthrough to resolve the lack of objective indicators on the diagnosis of TCM syndrome because of its high sensitivity and including abundant information of the images and spectra. In view of fuzzy and complicated mappings between tongue and syndrome, aiming at the defects of the acquisition methods of tongue information and its processing mode which extracts the features by fragmenting the integrative information, a new idea is proposed that the specific spectral indices pool be extracted after acquiring the hyperspectral data cube of tongue by hyperspectral imaging technology and associating it as a whole because of the overlapping mixing of these characteristic information with syndrome in black-box mode by means of intergration of various linear and nonlinear data mining algorithms. The mechanisms of etiological factor and pathogenesis are analyzed from all angles by synthesis of specific spectral indices pool, clinical physiological and biochemical indicators and TCM indicators. Then a new mode of objective diagnosis for syndromes can be found.

[The research status and development of noninvasive glucose optical measurements].

Diabetes threatens the health of human beings. Because of the disadvantages of invasive glucose detection, Noninvasive glucose measurement which diabetics press for becomes the hotspot in both domestic and overseas academic circles. But up to now none of the available devices offers enough precision to clinical application. The principle, method, characteristics of optical spectrum measurements and current development at home and abroad are reviewed in the present paper, such as photoacoustic spectroscopy method, Raman spectrometry, fluorescence method, polarimetry, optical coherence tomography and near infrared spectroscopy. Then the problems and technical analysis of noninvasive glucose measurements as well as the development direction are discussed, and the dynamic spectrum is pointed out to be one of the most application prospect methods for noninvasive glucose measurement.

[The quality evaluation of dynamic spectrum data].

To eliminate the influence of all factors on non-invasive measurement precision of blood components by dynamic spectrum method during data acquisition process, a quality evaluation criterion of dynamic spectrum data needs to be established to improve the stability of the model and precision of the prediction. The number of stable wavelength as a quality evaluation index for the dynamic spectrum data was presented in this article after further analysis of 110 samples, which were all obtained by in vivo measurements, and 60 samples were picked up as the satisfactory samples. BP artificial neural network was used to establish the calibration model of subjects' total cholesterol, glucose and hemoglobin values against dynamic spectrum data. The prediction result of the experiment group was improved compared with the control group. The average relative error was decreased from 13.8%, 15.8% and 5.4% to 6.5%, 6.5% and 2.1% respectively, by which the effectiveness of the number of stable wavelength as a quality evaluation index could be proved. By evaluating the quality of the dynamic spectrum data measured, more reliable prediction result can be obtained, which can make the non-invasive measurement of the blood components come to the clinical application sooner.

[Research on the blood components detecting by multi-optical path length spectroscopy technique].

To discuss the feasibility of using the serum's multi-optical path length spectroscopy information for measuring the concentration of the human blood components, the automatic micro-displacement measuring device was designed, which can obtain the near-infrared multi-optical path length from 0 to 4.0 mm (interval is 0.2 mm) spectra of 200 serum samples with multioptical path length spectrum of serum participated in building the quantitative analysis model of four components of the human blood: glucose (GLU), total cholesterol (TC), total protein (TP) and albumin (ALB), by mean of the significant non-linear spectral characteristic of blood. Partial least square (PLS) was used to set up the calibration models of the multi-optical path length near-infrared absorption spectrum of 160 experimental samples against the biochemical analysis results of them. The blood components of another 40 samples were predicted according to the model. The prediction effect of four blood components was favorable, and the correlation coefficient (r) of predictive value and biochemical analysis value were 0.9320, 0.9712, 0.9462 and 0.9483, respectively. All of the results proved the feasibility of the multi-optical path length spectroscopy technique for blood components analysis. And this technique established the foundation of detecting the components of blood and other liquid conveniently and rapidly.

Research Progress on PARP14 as a Drug Target.

Poly-adenosine diphosphate-ribose polymerase (PARP) implements posttranslational mono- or poly-ADP-ribosylation modification of target proteins. Among the known 18 members in the enormous family of PARP enzymes, several investigations about PARP1, PARP2, and PARP5a/5b have been launched in the past few decades; more specifically, PARP14 is gradually emerging as a promising drug target. An intact PARP14 (also named ARTD8 or BAL2) is constructed by macro1, macro2, macro3, WWE, and the catalytic domain. PARP14 takes advantage of nicotinamide adenine dinucleotide (NAD+) as a metabolic substrate to conduct mono-ADP-ribosylation modification on target proteins, taking part in cellular responses and signaling pathways in the immune system. Therefore, PARP14 has been considered a fascinating target for treatment of tumors and allergic inflammation. More importantly, PARP14 could be a potential target for a chemosensitizer based on the theory of synthetic lethality and its unique role in homologous recombination DNA repair. This review first gives a brief introduction on several representative PARP members. Subsequently, current literatures are presented to reveal the molecular mechanisms of PARP14 as a novel drug target for cancers (e.g., diffuse large B-cell lymphoma, multiple myeloma, prostate cancer, and hepatocellular carcinoma) and allergic inflammatory. Finally, potential PARP inhibitor-associated adverse effects are discussed. The review could be a meaningful reference for innovative drug or chemosensitizer discovery targeting to PARP14.

Interaction between Galectin-9/TIM-3 pathway and follicular helper CD4+ T cells contributes to viral persistence in chronic hepatitis C.

Both Galectin 9 (Gal-9)/T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) pathway and follicular helper CD4+ T (Tfh) cells play important roles in persistent hepatitis C virus (HCV) infection. Thus, we aimed to investigate the regulatory role of interaction between Gal-9/TIM-3 pathway and Tfh cells in chronic hepatitis C. A total of 44 chronic hepatitis C patients and 19 normal controls (NCs) were enrolled in this study. Purified CD4+ T cells were cultured by TIM-3 Fc protein, recombinant Gal-9, or IL-21 for 48h. TIM-3 expression, Tfh proportion, and IL-21 production was measured, respectively. The immunomodulatory role of Gal-9/TIM-3 and IL-21 was also investigated in HCV cell culture system in vitro. We found that the percentage corresponding to both TIM-3-positive and CXCR5+ICOS+ Tfh cells within CD4+ T cells, which correlated with HCV RNA replication, was significantly elevated in patients with chronic hepatitis C in comparison with those in NCs. Moreover, blockade of Gal-9/TIM-3 pathway by TIM-3 Fc protein increased Tfh cells proportion, IL-21 mRNA and protein expression within purified CD4+ T cells, while activation of Gal-9/TIM-3 signaling by Gal-9 stimulation decreased IL-21 production in both patients with chronic HCV infection and healthy individuals. Meanwhile, high concentrations (100 and 200ng/mL) of IL-21 stimulation also elevated TIM-3 expression on CD4+ T cells in chronic hepatitis C. Furthermore, TIM-3 blockage and IL-21 stimulation suppressed mRNA expressions of HCV-induced antiviral proteins (myxovirus resistance A and oligoadenylate synthetase) in Huh7.5 cells without affecting viral replication in HCV cell culture system. The interaction between Gal-9/TIM-3 pathway and Tfh cells contributed to viral persistent in chronic HCV infection, which might be pivotal for development of new therapeutic approaches for chronic hepatitis C.

miR-29a promotes hepatitis B virus replication and expression by targeting SMARCE1 in hepatoma carcinoma.

AIM: To investigate the functional role and underlying molecular mechanism of miR-29a in hepatitis B virus (HBV) expression and replication. METHODS: The levels of miR-29a and SMARCE1 in HBV-infected HepG2.2.15 cells were measured by quantitative real-time PCR and western blot analysis. HBV DNA replication was measured by quantitative PCR and Southern blot analysis. The relative levels of hepatitis B surface antigen and hepatitis B e antigen were detected by enzyme-linked immunosorbent assay. The Cell Counting Kit-8 (CCK-8) was used to detect the viability of HepG2.2.15 cells. The relationship between miR-29a and SMARCE1 were identified by target prediction and luciferase reporter analysis. RESULTS: miR-29a promoted HBV replication and expression, while SMARCE1 repressed HBV replication and expression. Cell viability detection indicated that miR-29a transfection had no adverse effect on the host cells. Moreover, SMARCE1 was identified and validated to be a functional target of miR-29a. Furthermore, restored expression of SMARCE1 could relieve the increased HBV replication and expression caused by miR-29a overexpression. CONCLUSION: miR-29a promotes HBV replication and expression through regulating SMARCE1. As a potential regulator of HBV replication and expression, miR-29a could be a promising therapeutic target for patients with HBV infection.

Notch Signaling Modulates the Balance of Regulatory T Cells and T Helper 17 Cells in Patients with Chronic Hepatitis C.

The imbalance of regulatory T cells (Tregs) and T helper 17 (Th17) cells contributes to the persistent hepatitis C virus (HCV) infection. However, modulatory factors associated with Tregs-Th17 balance were not fully elucidated. A recent study demonstrated an immunoregulatory strategy by inactivation of Notch signaling to reverse the disequilibrium of Tregs-Th17 cells in immune thrombocytopenia. Thus, the aim of this study was to assess the effect of Notch signaling in regulating the functions of Tregs and Th17 cells in chronic hepatitis C. A total of 46 patients with chronic hepatitis C and 17 normal controls (NCs) were enrolled. mRNA expressions of Notch1 and Notch2 were semiquantified by real-time reserve polymerase chain reaction. Percentages of Tregs-Th17, levels of key transcriptional factors, and cytokine productions were measured in response to treatment by DAPT, a γ-secretase inhibitor to suppress Notch signaling. We found that Notch1 and Notch2 mRNAs were significantly elevated in peripheral blood mononuclear cells from chronic hepatitis C patients compared with those from NCs. DAPT treatment reduced Th17 response by downregulation of RORγt expression and interleukin (IL)-17/IL-22 secretion. Tregs proportion, FoxP3 expression, and IL-10 production did not change significantly with DAPT treatment in chronic hepatitis C; however, blockage of Notch signaling inhibited the suppressive function of Tregs. Moreover, effective anti-HCV therapy not only reduced Notch1 and Notch2 expression but also decreased Tregs and Th17 proportions. The current data provided a novel mechanism underlying the modulation of Treg-Th17 balance. The link between Notch signaling and Th cells might lead to a new intervention for breaking immunotolerance of chronic HCV infection.

[Redox reactions of Sep15 and its relationship with tumor development].

BACKGROUND & OBJECTIVE: Sep15 is a selenium-containing protein identified in 1998. This protein may be involved in cancer etiology and it may have redox function. The objective of this study was to investigate the relationship between the redox function of Sep15 and tumor development. METHODS: The full-length DNA sequence of Sep15 was obtained by RT-PCR and then recombined to eukaryotic expression vector pcDNA3.1(+). The BEL-7402- Sep15 cell line, which expressed the high levels of Sep15 by transfecting the cultured hepatocarcinoma cell line BEL-7402 with pcDNA3.1-Sep15 was generated. From morphologic investigation, cell growth curve, clone formation and nude mice tumor growth curve, the relationship between Sep15 and hepatocarcinoma cell line BEL-7402 was determined. Furthermore, the redox reaction of sep15 was detected by MTT assay. RESULTS: There was no distinct effect of transfection of Sep15 gene on BEL-7402-Sep15 cell. The cell survival rate was drastically different between BEL-7402-Sep15 cell and both BEL-7402- pcDNA cell and BEL-7402-Sep15 cell after foreign H2O2 reactive oxygen stress (P<0.05). CONCLUSION: Transfecting Sep15 gene did not influence the growth characteristics of BEL-7402 cell line and Sep15 may have redox function.