Human Immunodeficiency Virus Type 1 RNA Genital Tract Shedding After Cryotherapy for Cervical Intraepithelial Neoplasia in Western Kenya.

This prospective study of 39 women living with human immunodeficiency virus (HIV) on antiretroviral therapy in Western Kenya aimed to quantify genital tract HIV-1 RNA (GT-HIV RNA) shedding before and after cryotherapy for cervical intraepithelial neoplasia. Most GT-HIV RNA shedding was detected precryotherapy, suggesting that cryotherapy was not the primary cause of shedding.

Construction of multifunctional porcine acellular dermal matrix hydrogel blended with vancomycin for hemorrhage control, antibacterial action, and tissue repair in infected trauma wounds.

Prevention of bacterial infection and reduction of hemorrhage, the primary challenges posed by trauma before hospitalization, are essential steps in prolonging the patient's life until they have been transported to a trauma center. Extracellular matrix (ECM) hydrogel is a promising biocompatible material for accelerating wound closure. However, due to the lack of antibacterial properties, this hydrogel is difficult to be applied to acute contaminated wounds. This study formulates an injectable dermal extracellular matrix hydrogel (porcine acellular dermal matrix (ADM)) as a scaffold for skin defect repair. The hydrogel combines vancomycin, an antimicrobial agent for inducing hemostasis, expediting antimicrobial activity, and promoting tissue repair. The hydrogel possesses a porous structure beneficial for the adsorption of vancomycin. The antimicrobial agent can be timely released from the hydrogel within an hour, which is less than the time taken by bacteria to infest an injury, with a cumulative release rate of approximately 80%, and thus enables a relatively fast bactericidal effect. The cytotoxicity investigation demonstrates the biocompatibility of the ADM hydrogel. Dynamic coagulation experiments reveal accelerated blood coagulation by the hydrogel. In vivo antibacterial and hemostatic experiments on a rat model indicate the healing of infected tissue and effective control of hemorrhaging by the hydrogel. Therefore, the vancomycin-loaded ADM hydrogel will be a viable biomaterial for controlling hemorrhage and preventing bacterial infections in trauma patients.

[Research progress on chemical constituents, pharmacological action and quality control of Scutellaria barbata].

Scutellaria barbata is a recognized anti-cancer traditional Chinese medicine, with the effects of clearing heat and detoxi-fication, dispelling blood stasis and stopping bleeding, diuresis and detumescence. At present, terpenoids, flavonoids, polysaccharides and volatile oils have been isolated from S. barbata, which have many pharmacological effects, such as resisting tumor, virus, bacteria and oxidation, and immunomodulation. This paper reviews the studies on the chemical constituents, pharmacological action and quality control of S. barbata, in the expectation of providing ideas and references for the further development and studies of S. barbata.

[Evaluation of Schneiderian membrane state using fiber optic endoscope during maxillary sinus floor elevation with lateral window].

Objective: To observe the status of the sinus membrane using fiber optic endoscope during the lateral window approach sinus floor elevation to provide a reference for clinicians when evelvating the sinus mucoperiosteum. Methods: Sixty-six patients (72 sides) who underwent maxillary sinus floor elevation in Beijing Ruicheng Stomatology Hospital from September 2016 to December 2019 were selected, including 40 males and 26 females, aged 26-80 years old [(56.2±11.5) years]. And fiber optic endoscopy was used to observe the maxillary mucoperiosteum during the operation. Results: The status of maxillary sinus mucoperiosteal during lateral window approach sinus floor elevation can be divided into four categories: ① Class Ⅰ, complete periosteal, no damage to mucoperiosteum; ②Class Ⅱ, periosteal injury, unexposed laminae propria; ③Class Ⅲ, periosteal Rupture, exposed lamina propria; ④ Class Ⅳ, mucoperiosteum perforation, rupture of periosteum, lamina propria and epithelial layer. A total of 72 operations were performed, including 18 cases of class I, 28 cases of class Ⅱ, 4 cases of class Ⅲ, and 22 cases of class Ⅳ. Conclusions: The status of maxillary sinus mucoperiosteal during lateral window approach sinus floor elevation can be divided into four categories. Fiberoptic endoscopy as a clinical auxiliary examination method can improve the operator's control of the status of the maxillary sinus membrane and assist the peeling of the mucosa.

Disruption of a Rice Chloroplast-Targeted Gene OsHMBPP Causes a Seedling-Lethal Albino Phenotype.

BACKGROUND: Chloroplast development is coordinately regulated by plastid- and nuclear-encoding genes. Although many regulators have been reported to be involved in chloroplast development, new factors remain to be identified, given the complexity of this process. RESULTS: In this study, we characterized a rice mutant lethal albinic seedling 1(las1)form of a 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (OsHMBPP) that was targeted to the chloroplasts. The LAS1 mutation caused the albino lethal phenotype in seedlings. Transmission electron microscopy indicated that las1 were defective in early chloroplast development. LAS1 is preferentially expressed in leaves, implying its role in controlling chloroplast development. The expression levels of many chloroplast-encoded genes were altered significantly in las1. The expression levels of nuclear-encoded gene involved in Chl biosynthesis were also decreased in las1. We further investigated plastidic RNA editing in las1 and found that the edit efficiency of four chloroplast genes were markly altered. Compared with WT, las1 exhibited defective in biogenesis of chloroplast ribosomes. CONCLUSIONS: Our results show that LAS1/OsHMBPP plays an essential role in the early chloroplast development in rice.

A scoping review of studies evaluating the education of health professional students about public health.

BACKGROUND: The purpose of this article is to identify and describe key components of research into the teaching methods of public health to postgraduate students. STUDY DESIGN: This is a systematic review of the published literature. METHODS: A detailed search of the literature based on keywords, Boolean operators, and free-text terms, identified from PubMed, Scopus and ERIC, published in the English language, between January 2000 and December 2017, was made. Teams of independent pairs agreed studies eligible for the review and performed data extraction. RESULTS: Of the 2,442 potential studies on education of public health professionals, 86 met all the inclusion criteria. Specific study designs, data collection, and techniques for data analysis varied widely across the individual studies, and there was a lack of consistency on the whole. The number of students in each study ranged from ten to 1,300. Forty-seven studies used quantitative methods to assess the effectiveness of teaching. Curriculum evaluation was the most common focus (n = 33), followed by course evaluation (n = 22). Few studies considered inequalities in terms of the types of students registered on the different courses/programs, with just three evaluating strategies to increase students from minority ethnic groups. Most studies evaluated short-term or medium-term outcomes rather than long-term impacts of education on students' careers or the relationship of education in meeting future public health workforce demands. CONCLUSIONS: This comprehensive systematic review identified a dearth of the literature on evaluations of approaches for teaching public health to health professions students. Those studies that had been published varied to such an extent in terms of their aims, methods, analysis, and results such that it was impossible to make any consistent comparisons of the observations reported in the studies. We conclude that evidence-based approaches for teaching public health to health professions students are either not sought by faculty and programs or, if conducted, not shared. As such, there are likely to be missed opportunities for ensuring that future graduates of health professions programs are as well prepared as possible to contribute to the health of the public.

[DNA barcoding of 4 species of cheyletid mites based on COI and 18S rRNA gene sequences].

OBJECTIVE: To analyze the sequences of mitochondrial cytochrome C oxidase subunit I gene (COI) and 18S ribosomal RNA gene (18S rRNA), so as to identify the feasible DNA barcodes for 4 species of cheyletid mites and improve the DNA barcoding database for cheyletid mites. METHODS: Cheyletid mite samples were collected from small-scale flour mills in Fuyang, Wuhu and Tongling cities of Anhui Province from May 2018 to July 2019, extracted and morphologically identified. Then, genomic DNA was extracted from a single cheyletid mite, and the COI and 18S rRNA gene sequences were obtained by PCR amplification, cloning and sequencing. The obtained sequences were aligned using the BLAST software. Multiple sequence alignment was done using the software ClustalX version 1.83 using the known gene sequences from cheyletid mites. The genetic distance was calculated using the software MEGA X, and the phylogenetic tree was created using the maximum likelihood method. RESULTS: The DNA barcoding results of Cheyletus malaccensis, C. carnifex and Cheletomorpha lepidopterorum were consistent with the morphological identification, while no sequences pertaining to Eucheyletia reticulate were retrieved in the GenBank database. The proportions of A + T were 69.6% and 55.1% in the COI and 18S rRNA sequences of 4 cheyletid mites species, respectively, and the numbers of base substitutions were 137 and 46, respectively. There were 154 to 321 and 58 to 99 inter-species variation loci in the COI and 18S rRNA gene sequences of 4 cheyletid mites species, respectively, and the intra-species genetic distance was all 0.020 or less in the COI and 18S rRNA gene sequences of 4 cheyletid mites species, with inter-species genetic distance of 0.235 to 0.583 and 0.078 to 0.114, respectively. Phylogenetic analysis based on COI and 18S rRNA genes showed that all four species of cheyletid mites were clustered into a branch with a 100% supportive rate, which was consistent with the morphological identification. CONCLUSIONS: Mitochondrial COI gene is superior to 18S rRNA gene as DNA barcodes for 4 species of cheyletid mites, which is more suitable to be used to investigate the phylogenetic relationship of at genus and species levels.

Correction: Exosomal Wnt-induced dedifferentiation of colorectal cancer cells contributes to chemotherapy resistance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

COX-2 potentiates cisplatin resistance of non-small cell lung cancer cells by promoting EMT in an AKT signaling pathway-dependent manner.

OBJECTIVE: To elucidate the effect of cyclooxygenase 2 (COX-2) on cisplatin resistance of NSCLC and its molecular mechanisms, with special attention to its pro-EMT (epithelial-mesenchymal transition) properties. MATERIALS AND METHODS: COX-2 levels were compared in two NSCLC cell lines, A549 and H460, by qPCR (quantitative Polymerase Chain Reaction) and Western blot. Cytotoxicity of cisplatin was also determined in the two cell lines using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The expression of EMT-related proteins and activation of AKT (protein kinase B) signaling were detected in H460 cells with ectopic COX-2 expression. RESULTS: Cisplatin-induced apoptosis was assessed in COX-2 overexpressing H460 cells by FACS. NS398, a COX-2 inhibitor, was also applied to determine EMT status and effect on cisplatin sensitivity in H460 cells. COX-2 levels were positively correlated with cisplatin resistance in both NSCLC cell lines tested. In response to COX-2 overexpression, EMT-related proteins, such as E-cadherin, were inhibited, while vimentin and N-cadherin were upregulated. The AKT signaling pathway was also activated in H460 cells. Ectopic expression of COX-2 potentiated cisplatin resistance of H460 cells, which was accompanied by decreased levels of apoptosis. Notably, NS398 effectively increased the cytotoxicity of cisplatin in A549 cells by inhibiting EMT and the AKT pathway. CONCLUSIONS: COX-2 might promote cisplatin resistance in NSCLC by promoting EMT through the AKT signaling pathway activation.

Exosomal Wnt-induced dedifferentiation of colorectal cancer cells contributes to chemotherapy resistance.

Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.

Correlation between the methylation of LIVIN gene and the pathogenesis of bone tumor.

OBJECTIVE: We investigated the correlation between the methylation of LIVIN gene and the pathogenesis of bone tumor at the molecular level, in order to improve the treatment method and enhance the cure rate of bone tumor. PATIENTS AND METHODS: The expression level of Livin protein was detected using Western blot analysis, and its expressions in control group and patients were detected by immunohistochemistry. The methylation frequency of LIVIN gene was calculated by direct sequencing. Finally, the prognosis of treatment was investigated by follow-up. RESULTS: The experiment found that Livin protein was not expressed in normal cells, while its expression rate was about 71.4% in 112 patients. The methylation frequency of LIVIN gene was gradually decreased with the increase of clinical stage, and had no significant relationship with age and sex. The prognosis experiment indicated that the lower the methylation frequency of LIVIN gene was, the shorter the survival time would be. CONCLUSIONS: The methylation of LIVIN gene was closely related to the pathogenesis of bone tumor, which may be one of the important factors to induce the formation of a bone tumor. In addition, the methylation frequency of LIVIN gene could be used as a biomarker for the prognosis of bone tumor treatment.

Application of pyrite and chalcopyrite as sensor electrode for amperometric detection and measurement of hydrogen peroxide.

The sensing performance of solid-state amperometric sensors based on natural sulfide minerals, i.e., pyrite and chalcopyrite, has been characterized for the detection and measurement of hydrogen peroxide (H2O2) in aqueous medium. The sensors showed a wide linear relationship range between response current and the concentration of H2O2 from 1.0 × 10-5 mol L-1 to 1.0 × 10-2 mol L-1 and 1.0 × 10-4 mol L-1 to 3.0 × 10-2 mol L-1 for pyrite and chalcopyrite, respectively. The limit of detection (LOD) was as low as 8.6 × 10-6 mol L-1 and 5.2 × 10-5 mol L-1 (S/N = 3), respectively. The electrodes exhibited great sensitivity, repeatability and short response time (less than 5 s). The results show that pyrite and chalcopyrite can be used as a natural, low cost, reliable and sensitive sensor for hydrogen peroxide detection, creating a new and high value application for the sulfide minerals.

Genetic analysis of a hybrid sterility gene that causes both pollen and embryo sac sterility in hybrids between Oryza sativa L. and Oryza longistaminata.

Oryza longistaminata originates from African wild rice and contains valuable traits conferring tolerance to biotic and abiotic stress. However, interspecific crosses between O. longistaminata and Oryza sativa cultivars are hindered by reproductive barriers. To dissect the mechanism of interspecific hybrid sterility, we developed a near-isogenic line (NIL) using indica variety RD23 as the recipient parent and O. longistaminata as the donor parent. Both pollen and embryo sac semi-sterility were observed in F1 hybrids between RD23 and NIL. Cytological analysis demonstrated that pollen abortion in F1 hybrids occurred at the early bi-nucleate stage due to a failure of the first mitosis in microspores. Partial embryo sacs in the F1 hybrids were defective during the functional megaspore formation stage. Most notably, nearly half of the male or female gametes were aborted in heterozygotes S40iS40l, regardless of their genotypes. Thus, S40 was indicated as a one-locus sporophytic sterility gene controlling both male and female fertility in hybrids between RD23 and O. longistaminata. A population of 16 802 plants derived from the hybrid RD23/NIL-S40 was developed to fine-map S40. Finally, the S40 locus was delimited to an 80-kb region on the short arm of chromosome 1 in terms with reference sequences of cv. 93-11. Eight open reading frames (ORFs) were localized in this region. On the basis of gene expression and genomic sequence analysis, ORF5 and ORF8 were identified as candidate genes for the S40 locus. These results are helpful in cloning the S40 gene and marker-assisted transferring of the corresponding neutral allele in rice breeding programs.

Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies.

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal anti-inflammatory drugs, fish oils, vitamin E and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib.

Differentiation-inducing effects of betamethasone on human glioma cell line U251.

We studied the differentiation-inducing effect of beta-methasone on human glioma cell line U251 cultured in vitro, and the underlying mechanism. U251 cells were divided into two groups: control group cells, cultured in Dulbecco's Modified Eagle's medium containing 10% fetal bovine serum; and medication group cells, treated with 15 µM betamethasone. Morphological cell changes were observed by inverted microscope, cell cycle changes were ascertained by flow cytometry, and vimentin expression was checked by immunocytochemistry. The expression levels of extracellular signal-regulated protein ki-nase (ERK), phosphorylated ERK (pERK), and glial fibrillary acidic protein (GFAP) were assessed by western blot. Compared with the control group, U251 cell processes increased significantly, but declined 96 h after betamethasone took effect. After 48 h, the percentage of S-phase cells decreased significantly (28.77 to 20.42%; P = 0.014); the percent-age of strongly positive vimentin cells decreased significantly (91 to 51%; P = 0.0092); and the ratio of expression of GFAP protein to the internal control ß-actin increased significantly (0.24 to 0.53; P = 0.1). The level of ERK protein did not change significantly 48 and 96 h after the action of betamethasone, and the pERK/ERK ratios were 0.37 and 0.23, respectively, which were significantly reduced compared with the control group (P = 0.028 and 0.006). Betamethasone has a significant effect on the induction and differentiation of U251 cells, and its mechanism may be related to the inhibition of the abnormal activation of the ERK signal pathway.

A TALEN-based specific transcript knock-down of PIWIL2 suppresses cell growth in HepG2 tumor cell.

OBJECTIVES: PIWIL2 is widely expressed in various tumours and implicated in playing a role in tumourigenesis. For a more thorough study of PIWIL2 functions in tumour cells, we aimed to establish PIWIL2-specific transcript knock-down/knockout HepG2 cell lines using transcription activator-like effector nuclease (TALEN) technology. Furthermore, we proposed to use the cell models to explore PIWIL2 functions in TGF-ß signalling in HepG2 cells. HepG2s are human hepatocellular carcinoma cells. MATERIALS AND METHODS: We established PIWIL2 knock-down or knock-out cell lines in HepG2 using TALEN technology. Next, we sought to use the cell line models to investigate effects of full length PIWIL2-specific transcripts in cell proliferation induced by TGF-ß. RESULTS: First, we established PIWIL2-specific transcript mono-allele and bi-allele knockout HepG2 cell lines. By using the cell line models, we found that specific transcript knockdown of full length PIWIL2 can suppress cell proliferation, while ectopic expression of PIWIL2 enhanced proliferation of HepG2 by suppressing the TGF-ß pathway. Furthermore, we demonstrated that PIWIL2 can interact with HSP90 to prevent formation of HSP90-TßR complexes, which promote degradation of TßRs. CONCLUSIONS: Taken together, our study revealed critical negative regulation of TGF-ß signalling by PIWIL2 in HepG2 tumour cells, and provided an effective strategy to study specific gene transcript functions in cells.

A clinical analysis of uterine artery embolisation in the treatment of placenta praevia or placenta praevia state.

The aim of this study was to investigate the efficiency of uterine artery embolisation (UAE) for postpartum haemorrhage (PPH) related to placenta praevia. A total of 45 women with placenta praevia or placenta praevia state underwent UAE before inducing labour. The locations of uterine artery and placenta were determined through selective and super-selective catheterisation into the internal iliac artery and uterine artery digital subtraction angiography (DSA). The target arteries were then super-selectively catheterised and embolised using small pieces of gelatin sponge. The above processes were repeated until the darkly stained areas of placenta were no longer developing. The success rate of UAE was 100%. There was no longer haemorrhage after embolisation for all the cases of labour induction and the average volume of blood loss was 56 ml. UAE is an effective, reliable and minimally traumatic treatment method for preventing postpartum haemorrhage after induction of labour in patients with placenta praevia state.

Identification of a novel human testicular interstitial gene, RNF148, and its expression regulated by histone deacetylases.

Multiple genes are restrictively expressed in mammalian testicular tissues, and they play important roles in the complex process of spermatogenesis. Investigation of these genes and their expression regulation mechanisms is valuable to elucidate the molecular process of spermatogenesis. In this study, we identified a novel human gene, ring finger protein 148 (RNF148) that is abundantly expressed in testes and slightly expressed in pancreas. In situ hybridization analysis showed that RNF148 messenger RNA was mainly present in the interstitial cells of human testicular tissues, and immunohistochemical analysis confirmed protein levels in that location. Treatment with histone deacetylase inhibitor trichostatin A activated the expression of RNF148 messenger RNA in a time- and concentration-dependent manner in HEK293T and HeLa cells, neither of which normally express RNF148. Chromatin immunoprecipitation analysis showed that trichostatin A treatment increased the binding of acetylated histone H3 to the RNF148 gene promoter. We identified a novel human testicular interstitial gene and observed that histone deacetylases regulate RNF148 expression.