HPV16-miRNAs exert oncogenic effects through enhancers in human cervical cancer.

BACKGROUND: Cervical cancer is a human papillomavirus (HPV)-related disease. HPV type 16 (HPV16), which is the predominant cause of cervical cancer, can encode miRNAs (HPV16-miRNAs). However, the role of HPV16-miRNAs in the pathogenesis of cervical cancer remains unclear. METHODS: Human cervical cancer cell lines SiHa (HPV16-positive) and C33A (HPV-negative), and cervical cancer tissues were collected to investigate the expression levels of two HPV16-miRNAs (HPV16-miR-H1 and HPV16-miR-H6). The overexpression and knockdown of HPV16-miR-H1 and HPV16-miR-H6 were performed using the lentiviral vector system and miRNA inhibitors, respectively. RNA-sequencing (RNA-seq) analysis and H3K27ac chromatin immunoprecipitation and sequencing (CHIP-seq) experiments were utilized to explore the roles of HPV16-miR-H1 and HPV16-miR-H6 facilitated by enhancers. CCK8, EdU, transwell, and wound healing assays were performed to verify the effects of HPV16-miR-H1 and HPV16-miR-H6 on cell proliferation and migration. RESULTS: HPV16-miR-H1 and HPV16-miR-H6 were highly expressed in both SiHa cells and tissue samples from HPV16-positive cervical cancer patients. RNA-seq analysis showed that HPV16-miR-H1 and HPV16-miR-H6 induced the upregulation of numerous tumor progression-associated genes. H3K27ac CHIP-seq experiments further revealed that HPV16-miR-H1 and HPV16-miR-H6 modulated the expression of critical genes by regulating their enhancer activity. The functional study demonstrated that HPV16-miR-H1 and HPV16-miR-H6 increased the migratory capacity of SiHa cells. CONCLUSIONS: Our data shed light on the role of HPV16-encoded miRNAs in cervical cancer, particularly emphasizing their involvement in the miRNA-enhancer-target gene system. This novel regulatory mechanism of HPV16-miRNAs provides new insights and approaches for the development of therapeutic strategies by targeting HPV16-positive cervical cancer.

Inhibitory effects and mechanisms of insoluble humic acids on internal phosphorus release from the sediments.

Release of phosphorus (P) from the sediments plays a critical role in the eutrophication of aquatic environments. Humic acids (HA), as the main form of carbon storage in the sediments, has essential impacts on the biogeochemical cycle of phosphorus in aquatic systems. Nevertheless, previous studies mainly concentrated on the competitive adsorption of HA solution and P on metal oxides and soils, with little attention paid to the effects of insoluble humic acids (IHA) on P sorption by and release from the sediments. Herein, an investigation on the rivers and lakes in Sichuan Province, China, found that there was a significantly positive correlation between the maximum P adsorption capacity (Qmax) of sediments and IHA contents (p < 0.01), but a significantly negative correlation between the zero equilibrium P concentration (EPC0) and IHA concentrations (p < 0.01). This indicated that IHA might have an inhibitory effect on the release of P from the sediments, which was verified by batch adsorption experiments and static incubation experiments. Adsorption experiments indicated that IHA can promote P adsorption by sediments. With the increase of IHA addition (from 0 to 20 mg/g) in the sediments, Qmax of sediments increased (from 0.516 to 0.911 mg/g), while EPC0 decreased greatly (from 0.264 to 0.005 mg/L). Increases in Fe (Ⅲ) bound-P, Al bound-P and humic bound-P caused by IHA were responsible for this promoting effect. Incubation experiments illustrated that IHA addition can efficiently inhibit P release from the sediments. After 32 days incubation, P concentration in the overlying water of control group (without IHA addition) was 0.651 mg/L, which was 13.29-40.69 times higher than those (0.016-0.049 mg/L) in the test groups (with 5 %-20 % IHA addition). The analysis of P species in sediments showed that transformation from loosely adsorbed-P and Fe (Ⅲ) bound-P to Al bound-P and humic bound-P was responsible for this inhibition of P release by IHA. This study demonstrated that IHA, differing from readily degradable or dissolved organic matter, have great inhibitory effects on internal P release, which provided a novel insight into the association between carbon burial and internal P release and even the management of water eutrophication.

Actinobacillus ureae may be a critical pathogen in patients with predispositions: A case report and review of the literature.

RATIONALE: Actinobacillus ureae (A. ureae) is an unusual commensal of human respiratory flora, rarely causing human infection. The predisposing factors, identification, clinical features, and antibiotic therapy of A. ureae are seldomly reported. Herein, we present a case of 64-year-old man affected by A. ureae pneumonia after intracranial surgery. PATIENT CONCERNS AND DIAGNOSES: A 64-year-old male was admitted with vomiting, drowsiness, and a severe disturbance of consciousness and was later diagnosed with cerebral hemorrhage by computed tomography images. After a craniocerebral surgery, the patient suffered from intractable pneumonia, experiencing treatment failure with multiple anti-bacterial agents. Sputum culture yield pure colonies of A. ureae, confirmed by matrix-assisted laser desorption/ionization time of flight and 16S rRNA gene sequencing. INTERVENTIONS: Minocycline (100 mg p.o. per 12 hours) with a course of 15 days was administrated for this patient. OUTCOMES: The respiratory symptoms, presenting as intermittent coughing with purulent and yellowish sputum, were gone. A 3-month follow-up examination showed a complete resolution of radiological findings. LESSONS: Clinically, the actual incidence of A. ureae pneumonia may be higher than that we generally recognized, and clinicians should consider A. ureae as a possible etiologic agent in patients with predispositions. Currently, A. ureae may be susceptible to penicillin, ampicillin, and third-generation cephalosporins. Other antibacterial agents, such as tetracycline, amoxicillin/clavulanic acid, and aminoglycosides also respond well and can be a choice in the treatment of A. ureae infections.

CCL5 might be a prognostic biomarker and associated with immuno-therapeutic efficacy in cancers: A pan-cancer analysis.

Purpose: Chemokine ligand 5 (CCL5), a vital member of the CC chemokine family, plays diverse roles in tumorigenesis, metastasis, and prognosis in various human tumors. However, no pan-cancer analysis has been conducted to illustrate its distinctive effects on clinical prognosis via underlying mechanisms and biological characteristics. Methods: Herein, we exploited the existed public bioinformatics database, primarily TCGA database and GTEx data, to comprehensively analyze the value of CCL5 involved in patient prognosis. Results: This study found that CCL5 was excessively expressed in most tumors and significantly associated with clinical prognosis in 10 out of 33 types of tumors. Notably, CCL5 might be an independent predictive biomarker of clinical outcome in SKCM patients, confirmed by univariate and multivariate Cox regression analysis. Furthermore, we acquired the genetic alteration status of CCL5 in multiple types of tumor tissues from TCGA cohorts. We revealed a potential correlation between the expression level of CCL5 and tumor mutational burden in 33 types of tumors. In addition, data showed that DNA methylation was associated with CCL5 gene expression in THCA, PRAD, LUSC, and BRCA cancers. Immune infiltration and immune checkpoints are fine indexes for evaluating immunotherapy. We uncovered that CCL5 was negatively correlated with the immune infiltration of CD8+ T cell, CD4+ T cell, macrophages, and gamma delta T cells in BRCA-basal and CESC tumors, while a significant positive correlation was observed in BLCA, COAD and other 7 types of tumors. Besides, CCL5 was closely associated with the immune checkpoint molecules in 8 types of tumors. The TIDE score was less in the CCL5 high-expressed group than in the CCL5 low-expressed group in SKCM patients, which indicated that CCL5 might be a fine monitor of immune response for immunotherapy. GO enrichment analysis data uncovered that cytokine-cytokine receptor interaction and chemokine signaling might be involved in the role of CCL5 in regulating tumor pathogenesis and prognosis. Conclusion: In conclusion, CCL5 was preliminarly identified as a biomarker of immune response and prognosis for tumors patients via our first comprehensive pan-cancer analysis.

Dispersed cobalt embedded nitrogen-rich carbon framework activates peroxymonosulfate for carbamazepine degradation: cobalt leaching restriction and mechanism investigation.

Metal leaching is a key issue in cobalt-based catalysts/PMS systems, which results in the decline of catalytic ability and serious secondary pollution. Hence, a nitrogen-rich carbon framework with cobalt node (Co-NC-920) with low cobalt leaching was synthesized based on zeolite imidazole framework (ZIF) and g-C3N4 to activate peroxymonosulfate (PMS) for the degradation of carbamazepine (CBZ). With the restriction of nitrogen-rich carbon framework, cobalt can disperse better and form stable cobalt-nitrogen bonds, thus only 0.09 mg/L cobalt ions were leached in the solution. More than 99.9% of CBZ can be removed within 30 min of PMS addition. Further investigation revealed that 1O2, SO4•- and high-valent cobalt species were primarily responsible for CBZ degradation in the Co-NC-920/PMS system and different reactive oxygen species (ROS) were distinguished and quantified, finding 1O2 was predominant. The degradation process was realized by the coexistence of free radicals and non-free radicals. Moreover, CBZ degradation capacity of the catalyst was evaluated under the influence of common anions and in actual waterbody. Finally, the possible degradation pathways of CBZ were proposed and the toxicity of the intermediates was analyzed. This work provides a new approach for the synthesis of cobalt-based nitrogen-rich carbon catalysts with low leaching and high efficient.

Multifunctional Hybrid Interfacial Layers for High-Performance Inverted Perovskite Solar Cells.

Challenges remain hindering the performance and stability of inverted perovskite solar cells (PSCs), particularly for the nonstable interface between lead halide perovskite and charge extraction metal oxide layer. Herein, a simple yet scalable interfacial strategy to facilitate the assemble of high-performance inverted PSCs and scale-up modules is reported. The hybrid interfacial layer containing self-assembly triphenylamine and conjugated poly(arylamine) simultaneously improves the chemical stability, charge extraction, and energy level alignment of hole-selective interface, meanwhile promoting perovskite crystallization. Consequently, the correspondent inverted PSCs and modules achieve remarkable power conversion efficiencies (PCEs) of 24.5% and 20.7% (aperture area of 19.4 cm2 ), respectively. The PSCs maintain over 80% of its initial efficiency under one-sun equivalent illumination of 1200 h. This strategy is also effective to perovskite with various bandgaps, demonstrating the highest PCE of 19.6% for the 1.76-eV bandgap PSCs. Overall, this work provides a simple yet scalable interfacial strategy for obtaining state-of-the-art inverted PSCs and modules.

Effective peroxymonosulfate activation by natural molybdenite for enhanced atrazine degradation: Role of sulfur vacancy, degradation pathways and mechanism.

In this study, natural molybdenite (MoS2) was applied to activate peroxymonosulfate (PMS) for the removal of atrazine (ATZ) and its degradation mechanism was investigated. Molybdenite exhibits superior catalytic performance. The best condition for atrazine degradation efficiency (>99%) was obtained with molybdenite concentration of 0.4 g/L, PMS concentration of 0.1 mM, and ATZ concentration of 12 µM within 10 min under experimental conditions. Electron paramagnetic resonance (EPR) test and chemical probe test further proved that HO• and SO4•- played important roles in the molybdenite/PMS system, and SO4•- was dominant. Meanwhile, Electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS) tests showed that sulfur vacancies and edge sulfur played important roles in the system. Edge sulfur was conducive to Mo4+ exposure, while sulfur vacancy facilitated electron transfer and reduced Mo6+ back to Mo4+. Combined with DFT calculation, the role of sulfur in the degradation process was verified. Besides, five ATZ degradation pathways were proposed. Finally, the degradation ability of the molybdenite/PMS system for different pollutants and in actual water bodies was also explored. This work provided ideas for exploring the degradation of organic contaminants by natural minerals.

An Objective Diagnosis Model with Integrated Metabolic and Immunity Parameters for Phlegm-Dampness Constitution.

BACKGROUND: According to Chinese constitutional theory, people can be divided into nine constitutions, which represent distinctive vulnerability to different diseases such as metabolic syndrome, atherosclerosis, and immunity-related disease, and so forth in modern medicine, phlegm-dampness constitution (PDC) is one of the nine constitutions, which is susceptible to metabolic syndrome (MS) and atherosclerosis that associate with lipid metabolism and immunity dysregulation closely. OBJECTIVES: In this study, we aimed to investigate the metabolic and immunity profiles of phlegm-damp constitution (PDC), including metabolites, lymphocytes distribution, and inflammatory cytokines. METHODS: A total of 74 patients with PDC and 66 individuals with gentle constitution (GC) were enrolled in this study. We utilized biochemical methods to detect metabolic parameters, flow cytometry to survey T/B/NK/NKT lymphocyte subgroups distribution, and ELISA to assay inflammatory cytokines. RESULTS: The subjects with PDC had higher GLU, AI TC, TG, and LDL-C and lower HDL-C levels. The immunity profile indicated that PDC subjects had higher percentage of WBCs, neutrophils, lymphocytes, B cells, and natural killer T cells compared with subjects with GC (P < 0.05). Serum levels of IL-10 decreased significantly in the subjects with phlegm-damp constitution, whereas IL-12 levels increased dramatically in the PDC group compared with the GC group (both P < 0.05). Additionally, logistic regression identified four independent variables (GLU, TG, LDL-C, and lymphocytes) that were highly correlated with PDC (P < 0.05). The area under the curve of the receiver operating characteristic curve was 0.878, which indicated the data were reliable to distinguish the subjects with PDC from the ones with GC. CONCLUSION: Phlegm-damp constitution was prone to hyperglycemia and hyperlipidemia syndrome, promoting the occurrence and progression of metabolic-related diseases. Interestingly, proinflammatory cells and cytokines were activated in the PDC group as well. Our findings could offer a profile of early screening indicators to identify high-risk patients of metabolic- and immunity-related diseases from Chinese constitution.

Self-Assembled Donor-Acceptor Dyad Molecules Stabilize the Heterojunction of Inverted Perovskite Solar Cells and Modules.

The heterointerface between a semiconducting metal oxide and a perovskite critically impacts on the overall performance of perovskite solar cells (PVSCs). Herein, we report a feasible yet effective strategy to suppress the interfacial reaction between nickel oxide and the perovskite via chemical passivation with self-assembled dyad molecules, which leads to the simultaneous improvement of the power conversion efficiencies (PCEs) and operational lifetimes of inverted PVSCs. As a result, inverted PVSCs consisting of simple methylammonium iodide perovskites have achieved an excellent PCE of 20.94% and decent photostability with 93% of the initial value after 600 h of 1 sun equivalent illumination. Moreover, this strategy can be readily translated into slot-die fabrication of perovskite modules, achieving a high PCE of 14.90% with an area of 19.16 cm2 (no shade in the interconnecting area) and a geometrical fill factor of 93%. Overall, this work provides an effective strategy to stabilize the vulnerable heterointerface in PVSCs.

The evaluation of students' physical health based on the integration of family and school physical education / Avaliação da saúde física dos estudantes com base na integração da educação física familiar e escolar / Evaluación de la salud física de los estudiantes basada en la integración del deporte familiar y escolar

ABSTRACT In recent years, China has paid more and more attention to students' physical health, but it is difficult for schools to provide scientific guarantee for students' physical health evaluation. How to use scientific algorithm for accurate guidance has become the current hotspot. Based on this, this paper studies the evaluation model of students' physical health based on the integration of home and school sports. Firstly, this paper analyzes the research status of physical health evaluation at home and outside, then optimizes and improves the deficiencies in the integration of home and school sports in the current research hotspot, then applies SVM algorithm to the physical health evaluation model. Finally, the experimental results show that the SVM algorithm can objectively evaluate the integration of home and school sports, and can optimize the evaluation strategy according to the differences of students in the process of physical exercise, and the accuracy of physical health evaluation can reach more than 97%.

RESUMO Nos últimos anos, a China tem prestado cada vez mais atenção à saúde física dos estudantes, mas é difícil para as escolas fornecer garantias científicas para o processo de avaliação da saúde física dos estudantes. Como usar o algoritmo científico para orientação precisa tornou-se um ponto crucial. Com base nisso, este documento estuda o modelo de avaliação da saúde física dos estudantes com base na integração dos esportes domésticos e escolares. Em primeiro lugar, este artigo analisa o estado de investigação da avaliação da saúde física em casa e fora de casa, e, em seguida, otimiza e melhora as deficiências na integração dos esportes domésticos e escolares no atual foco de pesquisa, e, em seguida, aplica o algoritmo SVM ao modelo de avaliação da saúde física. Finalmente, os resultados experimentais mostram que o algoritmo SVM pode realizar a avaliação objetiva do processo de integração de esportes domésticos e escolares, e pode otimizar a estratégia de avaliação de acordo com as diferenças dos estudantes no processo de exercício físico, e a precisão da avaliação de saúde física pode atingir mais de 97%.

RESUMEN En los últimos años, China ha prestado cada vez más atención a la salud física de los estudiantes, pero es difícil para las escuelas brindar garantías científicas para la evaluación de la salud física de los estudiantes. Cómo utilizar el algoritmo científico para una guía precisa se ha convertido en el punto de acceso actual. Con base en esto, este trabajo estudia el modelo de evaluación de la salud física de los estudiantes basado en la integración de los deportes domésticos y escolares. En primer lugar, este artículo analiza el estado de la investigación de la evaluación de la salud física en el hogar y en el exterior, luego optimiza y mejora las deficiencias en la integración de los deportes en el hogar y la escuela en el punto de acceso de investigación actual. Luego aplica el algoritmo SVM al modelo de evaluación de la salud física. Finalmente, los resultados experimentales muestran que el algoritmo SVM puede evaluar objetivamente la integración de los deportes en el hogar y la escuela, y puede optimizar la estrategia de evaluación de acuerdo con las diferencias de los estudiantes en el proceso de ejercicio físico, y la precisión de la evaluación de la salud física puede alcanzar más del 97%.

Comparison of double antigen sandwich and indirect enzyme-linked immunosorbent assay for the diagnosis of hepatitis C virus antibodies.

BACKGROUND: The aim of this study is to compare double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) and indirect ELISA in the diagnosis of hepatitis C virus（HCV）infection. METHODS AND MATERIALS: A total of 176 samples from the Tumor Hospital Affiliated to Xin Jiang Medical University were utilized to comparison. All serum samples were tested using double-antigen sandwich ELISA and indirect ELISA. Cohen's kappa statistics were used to assess the agreement between the two assays, and multivariate analysis was used to evaluate risk factors for the discordance between the double-antigen ELISA and indirect ELISA. RESULTS: The positivities of indirect ELISA (Beijing Wantai), double-antigen sandwich ELISA (Beijing Wantai), and indirect ELISA (Beijing Jinhao) were 74.43%, 68.75%, and 73.30%, respectively. The agreement between the indirect ELISA (Beijing Wantai) and double-antigen sandwich ELISA (Beijing Wantai) was high (κ = 0.829;P < .001), and the agreement between the double-antigen sandwich ELISA (Beijing Wantai) and indirect ELISA (Beijing Jinhao) was high (κ = 0.847;P < .001). Variables associated with discordant results between the double-antigen sandwich and indirect ELISA in multivariate analysis were as follows: female (OR:1.462; P < .05), age (<35 years old; OR:3.667; P < .05), and cancer (suffer from malignant tumor; OR:3.621; P < .05). CONCLUSION: In detection of HCV, high agreement was found between the double-antigen sandwich ELISA and indirect ELISA. Female, younger age, and suffer from malignant tumor were significant risk factors for the discordance. Based on double-antigen sandwich ELISA has distinct methodological advantages over indirect ELISA. It is recommended for the diagnosis of HCV infection.

[Methylation Chip Screening and Verification of Differential Genes Related to Tuberculosis Infection].

OBJECTIVE: To screen the genes with significant changes in DNA methylation level in active tuberculosis patients, we used the methylation chips and expanded the sample size to verify candidate genes. METHODS: ① This study enrolled 9 cases of active tuberculosis patients, 3 cases of latent tuberculosis patients and 3 cases of healthy controls whose age and gender were all matched. Genome DNA was extracted from peripheral blood mononuclear cell in blood samples collected from these candidates, and bisulfite conversion treatment was then conducted. After hybridization with the Illumina HD 450K Infinium Mehtylation BeadChip, the results were compared between patients group and control group, and GO and KEGG pathway analyses were performed to evaluate the function of differentially expressed genes. ② We further enrolled 60 cases of active tuberculosis patients and 60 cases of health controls (age-and gender-matched), DNA was extracted from their peripheral blood and also followed bisulfite conversion treatment. Pyrosequencing method was used to detect the methylation levels of candidate genes (IFNGR2, PTPN6, CRK1, ATP6V0B, WIF1, DKK1 and SFRP1) screened by gene chip. RESULTS: Compared with healthy controls, the fragments in the patients that showed low methylation change accounted for the vast majority. Most of the methylation differential fragments (DMRs) were located in the main body region, followed by the upstream region of transcription initiation site, and the lowest DMRs distribution area was 3´UTR area. GO and Pathway analysis showed that the functions of the differentially methylated regions related genes are mainly enriched in the biological processes of the regulation of leukocyte differentiation, apoptosis, cytokine regulation and inflammatory response which are closely related to tuberculosis. There were 32 CpG sites involved in the verified 7 tuberculosis related genes, and 16 CpG locus showed significant difference (P<0.05), they were distributed in 6 genes: PTPN6, WIF1, CRK1, SFRP1, DKK1 and IFNGR2.Of these genes with significant difference, PTPN6 genes showed hypermethylation status and WIF1, CRK1, SFRP1, DKK1 and IFNGR2 genes exhibited demethylation status in the patients group compared to the health controls. SFRP1 and CRK-1 mRNA up-regulated in the patients group compared with health controls. CONCLUSION: In the course of MTB infection, the methylation status of genomic DNA is altered, and most of the differentially methylated regions (DMRs) are showed status of demethylation. The expressions ofSFRP1and CRK-1gene up-regulate in tuberculosis infection.

The Leukocyte VCS Parameters Compared with Procalcitonin, Interleukin-6, and Soluble Hemoglobin Scavenger Receptor sCD163 for Prediction of Sepsis in Patients with Cirrhosis.

BACKGROUND: Patients with liver cirrhosis have a high risk of sepsis and a poor prognosis. Recently, a new standard for sepsis (Sepsis-3) has been proposed in the general population. The Coulter Lh 750 hematology analyzer can evaluate mean volume, conductivity, scatter, and distribution width of leukocyte. We tried to use Sepsis-3 criteria to study the diagnostic value of volume, conductivity, and scattering (VCS) parameters in sepsis and infection in patients with liver cirrhosis compared with traditional infection markers (PCT, IL-6, sCDl63). METHODS: A blinded, cohort study was conducted in three different ED populations within three affiliated hospitals. A total of 249 patients with liver cirrhosis were enrolled in the study. According to the "Sepsis-3" consensus criteria, clinical history, and laboratory examination, the subjects were divided into sepsis (n = 54), patients with infections (n = 95), and patients without systemic infections (n = 100). The blood samples of the patients were collected at the time of ED admission and were evaluated for the detection of sepsis. RESULTS: The differences of MNV, MNS, MMV, MMS, MLV, NDW, and MDW in the three groups were statistically significant. In the diagnosis of sepsis in patients with liver cirrhosis, the sensitivity of combined detection of MMV and MDW was 88.89%; the specificity was 74%. This sensitivity was significantly better than the 83.3% achieved using 0.97 mg/L as the cutoff for sCD163. In the diagnosis of infection in cirrhosis, the sensitivity of combination of MNV and MMS was increased to 86.32%; the specificity was 92%. The sensitivity was the same as that achieved by using 0.31 ng/mL as the cutoff value of PCT, but the specificity increased. CONCLUSION: The leukocyte VCS parameter could be potential parameters for indicating sepsis and infection in patients with liver cirrhosis. The combined detection of MMV and MDW seemed to be helpful for the diagnosis of sepsis in these patients, and the combination of MNV and MMS could better indicate infection for them.

Study on interaction between human salivary α-amylase and sorghum procyanidin tetramer: Binding characteristics and structural analysis.

As one of receptors of the acquired membrane, human salivary α­amylase (HSA) plays an important role in the formation of caries. In vitro conditions, sorghum procyanidins (SPC) tetramer has a better inhibitory effect on the adhesion of Streptococcus mutans to hydroxyapatite than SPC-dimer and SPC-trimer. This study investigated the interaction mechanism between HSA and SPC-tetramer using spectroscopic techniques including fluorescence, UV-vis absorption, and circular dichroism (CD). Fluorescence data revealed that the fluorescence quenching of HSA by SPC-tetramer was a static quenching process, and that the SPC-tetramer was bound with HSA at the ratio of 1:1 in SPC-tetramer-protein complex. Meanwhile, the analysis of CD demonstrated that the conformation of HSA was altered in the presence of SPC-tetramer. The conformation changes of HSA might contribute to the reduction of the adhesion of cariogenic bacteria and finally decrease the occurrence of dental caries.

The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance.

BACKGROUND: According to recent clinical observations, deficient DNA mismatch repair (dMMR) is capable of improving antitumor effects of the PD-1/PD-L1 pathway, suggesting that dMMR may act as a prognostic indicator of PD-1/PD-L1 antibody drugs. In this study, we examined the dMMR and PD-1/PD-L1 expression, as well as explored the correlation of dMMR status with PD-1/PD-L1 expression in cervical cancer patients, in order to optimize cervical cancer patient selection for PD-1/PD-L1 antibody drug treatment, which is helpful to avoid adverse effects and keep costs manageable. METHODS: Sixty-six tissue samples from patients with squamous cell carcinoma were collected, and data of their clinical characteristics were also gathered. Based on these samples, the expression levels of MLH1, MSH2, and PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Moreover, PD-1/PD-L1 expression in tumor-invading lymphocytes (TILs) was detected by IHC as well. Six single-nucleotide-repeat markers of microsatellite instability (MSI), including NR-27, MONO-27, BAT-25, NR-24, NR-21, and BAT-26, were tested by capillary electrophoresis sequencer analysis. According to expression of MLH1, MSH2 and the MSI test, all 66 cases were divided into dMMR or proficient DNA mismatch repair (pMMR) groups. The comparisons of dMMR and PD-L1 in cancer cells and of PD-1/PD-L1 in TILs were conducted categorized by age, childbearing history, history of abortion, ethnicity, and cancer cell differentiation subgroup. Furthermore, PD-L1 levels in cancer cells and PD-1/PD-L1 in TILs were analyzed and compared in both dMMR and pMMR subgroups. RESULTS: Of the patient samples, 25.8% were associated with dMMR. PD-L1 in cancer cells, PD-L1 in TILs, and PD-1 in TILs took up 59.1%, 47.0%, and 60.6%, respectively. The data indicated that both dMMR and PD-L1 overexpression resulted from lower cancer differentiation, more incidences of childbearing, and a history of abortion. Abortion could significantly increase PD-1 expression levels in TILs. Additionally, more incidence of childbearing or older age (35-55 years) was able to upregulate PD-L1 expression in TILs. Statistical difference of PD-L1 in cancer cells could be observed between dMMR and pMMR subgroups. In the dMMR group, PD-L1 in cancer cells and PD-1 in TILs had no correlation (rs=0.161, p=0.537), but in the pMMR group, they had good correlation (rs=0.645, p<0.001). CONCLUSION: According to prior studies and our own experiments, PD-L1 in both cancer cells and TILs and PD-1 in TILs are widely observed in cervical cancer patients, indicating that there may be potential to apply PD-1/PD-L1 antibody drugs in cervical cancer. dMMR patients are associated with higher PD-L1 expression compared with pMMR ones, which suggested that PD-1/PD-L1 antibody drugs may work well in dMMR cervical cancer patients. Moreover, in patients with more incidences of childbearing or abortion, dMMR may be a molecular detection target for clinical application of PD-1/PD-L1 antibody drugs.

Development of a multi-marker model combining HE4, CA125, progesterone, and estradiol for distinguishing benign from malignant pelvic masses in postmenopausal women.

The purpose of this study was to evaluate HE4, CA125, progesterone (Prog), and estradiol (E2) for differentiating pelvic masses in postmenopausal women and aimed to build a multi-marker model which may improve the diagnostic value. HE4, CA125, Prog, and E2 were detected in 57 benign pelvic masses (BPM) and 92 epithelial ovarian cancer (EOC) patients. A total of 66.66 % of the BPM and EOC serum samples were used for building the differentiation model, and the remaining 33.33 % of the BPM and EOC serum samples were used for validation of the differentiation model. After comparing by Z score statistics, HE4 + CA125 + E2 model was chosen as the best multi-marker model. In the training group, the area under curve of the HE4 + CA125 + E2 model was 0.97 (0.93, 1.00), sensitivities of the model for distinguishing BPM from EOC, from early EOC, and from advanced EOC were 90.16, 86.21, and 95.65 %; specificities were 92.11, 92.11, and 92.11 %. In the validation group, sensitivities of HE4 + CA125 + E2 model for distinguishing BPM from EOC, from early EOC, and from advanced EOC were 96.77, 100.00, and 87.50 %, specificities were 84.21, 100.00, and 84.21 %. The multi-marker model showed significant improvement when compared to CA125 or HE4, and it might be an effective pelvic mass differentiation method.

Comparison of HE4, CA125, and ROMA Diagnostic Accuracy: A Prospective and Multicenter Study for Chinese Women With Epithelial Ovarian Cancer.

Risk of Ovarian Malignancy Algorithm (ROMA) combing human epididymis secretary protein 4 (HE4) and CA125 showed better diagnostic accuracy for epithelial ovarian cancer (EOC) when compared with HE4 or CA125 alone; however, other studies showed no or worse diagnostic accuracy. We aim to conduct a prospective and multicenter clinical trial to compare the diagnostic accuracy of HE4, CA125, and ROMA for EOC.A prospective and multicenter (n = 9) trial including 2481 individuals was performed in Chinese women. HE4, CA125, and ROMA diagnostic accuracy were evaluated according to different menopausal status and stages of EOC. Their diagnostic values were evaluated by the area under curve (AUC) and compared by the Z scores. Diagnostic specificity of other kinds of participants (n = 1098) was also evaluated.For discriminating between healthy control (HC) and EOC, only CA125 showed significant difference for discriminating HC and EOC in all the individuals when compared with HE4 and ROMA (P < 0.001 and P = 0.02, respectively), at the cutoff value of 31.5, the sensitivity (SN) and specificity (SP) were 88.6% and 97.1%. For discriminating between benign pelvic mass (BPM) and EOC, ROMA showed significant difference for discriminating BPM and EOC in the all individuals (P = 0.01 and P = 0.02, respectively) and the postmenopausal individuals (P = 0.03 and P = 0.04, respectively), at the cutoff value of 27.3 and 34.5, the SNs were 97.0% and 89.4%, SPs were 81.4% and 82.5%, separately. Within all kinds of diseases, there was no significant difference in specificity between CA125 and HE4.In conclusions, when HE4, CA125, and ROMA were compared with each other according to different menopausal status, and stages. Only CA125 showed significant difference for discriminating HC and EOC in all the individuals, and ROMA for discriminating BPM and EOC in the all individuals and postmenopausal individuals when compared with HE4 or CA125. HE4 has showed no significant difference in specificity with all kinds of diseases when compared with CA125.

[Analysis of BK viruria on the long term graft survival in renal transplant recipients].

OBJECTIVE: To observe the clearance of BK viruria and long-term graft survival in renal transplant recipients with BK virus (BKV) infection under the protocol of our center. METHODS: Urine was taken from 229 renal transplant recipients,who were transplanted between March 2006 to October 2008, for BKV cytological testing and real-time PCR for BKV DNA at 1, 3, 6, 9, and 12 months after transplantation. Graft biopsies were analyzed for SV40-T by immunohistochemical method. Recipients were treated according to the BKV infection protocol of our center and were monitored for BKV and graft function. All the patients were followed for at least 5 years. RESULTS: By 1 year post-transplant, urinary decoy cells, BK viruria, and BKV associated nephropathy (BKVAN) occurred in 78, 99, and 7 patients, respectively. The median followed-up time was 63.6 (3.0-88.0) months. After reduction of immunosuppression, 81 (81.8%) patients cleared BK viruria with a mean time of (12.1 ± 1.9) months. When compared with non-BKVAN patients, BKVAN patients had a higher median peak level of BK viruria (2.07 × 109 vs 9.28 × 105 copies/ml, P=0.002), lower frequency of clearance (3/7 vs 78/92, P=0.006), longer BK viruria clearance time ((45.4 ± 6.4) vs (8.7 ± 1.5) months, P=0.001). The 1, 3, 5-year graft survival in BK viruria patients were 99.0%, 95.9% and 89.6% respectively, which were not significantly different from those in non-BK viruria patients (97.7%, 95.5% and 93.7%, P=0.289). Graft function of BK viruria patients were not statistical significance compared with non-BK viruria patients (serum creatinine level 5 years post-transplant: (105.7 ± 30.9) vs (111.3 ± 4.6) µmol/L, P=0.322). Graft function of BKVAN patients at 5 years post-transplant was stable without significantly difference from non-BKVAN patients (serum creatinine level: (127.6 ± 41.0) vs (108.3 ± 39.3) µmol/L, P=0.204). CONCLUSION: On the premise of intensively and regularly BKV monitoring and preemptive reduction of immunosuppression, BK viruria and BKVAN can not impact on the long-term graft survival in renal transplant recipients.

Determination of reference intervals of serum levels of human epididymis protein 4 (HE4) in Chinese women.

BACKGROUND: To determine reference intervals for serum levels of human epididymis protein 4 (HE4) in Chinese women. METHODS: In this multicenter (n = 9) study, 618 healthy women, 767 patients with non-malignant diseases, and 951 patients with malignant tumors were enrolled. Serum levels of HE4 were measured in all patients using electrochemiluminescence immunoassays. The influence of age, menopause, malignancy status and other characteristics on the levels of HE4 was evaluated using univariate and multivariate analyses. Confidence intervals (2.5-97.5 %) were determined in different populations. RESULTS: There were significant differences in HE4 levels among groups with different ages, menopause or malignancy status. Higher levels of HE4 were detected in elder compared to younger, post- compare to pre- menopause and malignant compared to benign subjects. Multivariate analysis showed that menopause and malignancy status, as well as smoking and pelvic masses were independent factors involved in serum HE4 levels. In pre-menopause stage, the reference ranges of HE4 level were 29.30-68.79, 28.12-1284.83 and 34.75-981.91 pmol/L in healthy, benign and malignant populations, respectively. In post-menopause stage, the reference ranges are 35.96-114.43, 39.11-2208.70 and 39.40-1678.13 pmol/L for those populations. CONCLUSIONS: The present study has established the reference intervals of HE4 levels in pre- and post-menopause populations with different malignancy status.