Role of CXCR5+ CD8+ T cells in human hepatitis B virus infection.

The replication of HBV in hepatocytes can be effectively inhibited by lifelong antiviral therapy. Because of the long-term presence of HBV reservoirs, the virus rebound frequently occurs once the treatment is stopped, which poses a considerable obstacle to the complete removal of the virus. In terms of gene composition, regulation of B cell action and function, CXCR5+ CD8+ T cells are similar to CXCR5+ CD4+ T follicular helper cells, while these cells are characterized by elevated programmed cell death 1 and cytotoxic-related proteins. CXCR5+ CD8+ T cells are strongly associated with progression in inflammatory and autoimmune diseases. In addition, CXCR5 expression on the surface of CD8+ T cells is mostly an indicator of memory stem cell-like failure in progenitor cells in cancer that are more responsive to immune checkpoint blocking therapy. Furthermore, the phenomena have also been demonstrated in some viral infections, highlighting the duality of the cellular immune response of CXCR5+ CD8+ T cells. This mini-review will focus on the function of CXCR5+ CD8+ T cells in HBV infection and discuss the function of these CD8+ T cells and the potential of associated co-stimulators or cytokines in HBV therapeutic strategies.

Inhibition of HSPA8 by rifampicin contributes to ferroptosis via enhancing autophagy.

BACKGROUND AND AIM: Rifampicin is the most common pathogenic factor in anti-tuberculosis drug-induced liver injury (AT-DILI), the mechanisms that it promotes hepatocyte damage in AT-DILI are not yet to be thoroughly elucidated. In this study, we investigated the potential molecular mechanisms for ferroptosis involving rifampicin hepatotoxicity. METHODS: Animal and cell injury models of rifampicin were constructed, and the toxicity of rifampicin was assessed by physicochemical staining and cell viability assay. Next, flow cytometry was employed to detect changes in ferroptosis-related markers, and Western blotting was used to detect protein expression. Then, the important role of autophagy and ferroptosis was verified with small molecule compound intervention. RESULTS: We found that ferritinophagy-induced ferroptosis participates in the toxicity of rifampicin, and the mechanism is that rifampicin precisely activates high-throughput autophagy, which leads to the massive degradation of ferritin and the increase of free iron. Moreover, rifampicin exhibited conspicuous inhibition of Human 71 kDa heat shock cognate protein (HSPA8) that is intimately associated with Microtubule-associated protein light chain 3 isoform B (LC3B) expression, in turn, HSPA8 inducer attenuated intracellular autophagy flux. Of note, inducing HSPA8 or inhibition of autophagy and ferroptosis considerably relieved the hepatotoxicity of rifampicin in mouse model. CONCLUSIONS: The present study highlights the crucial roles of the HSPA8 and autophagy in ferroptotic cell death driving by rifampicin, particularly illumines multiple promising regulatory nodes for therapeutic interventions in diseases involving AT-DILI.

Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 8141 single pregnancies.

BACKGROUND: Noninvasive prenatal testing (NIPT) for fetal aneuploidies by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a first-tier aneuploidy screening test in clinical practices. With the development of whole-genome sequencing technology, small subchromosomal deletions and duplications that could not be detected by conventional karyotyping are now able to be detected with NIPT technology. METHODS: In the present study, we examined 8141 single pregnancies with NIPT to calculate the positive predictive values of each of the chromosome aneuploidies and the subchromosomal microdeletions and microduplications. RESULTS: We confirmed that the positive predictive values (PPV) for trisomy 13, trisomy 18, trisomy 21, and sex chromosome aneuploidy were 14.28%, 60%, 80%, and 45.83%, respectively. At the same time, we also found 51 (0.63%) positive cases for chromosomal microdeletions or microduplications but only 13 (36.11%) true-positive cases. These results indicate that NIPT for trisomy 21 detection had the highest accuracy, while accuracy was low for chromosomal microdeletion and microduplications. CONCLUSIONS: Therefore, it is very important to improve the specificity, accuracy, and sensitivity of NIPT technology for the detection of subchromosomal microdeletions and microduplications.

Dynamic analysis of a phytoplankton-fish model with the impulsive feedback control depending on the fish density and its changing rate.

This paper proposes and studies a comprehensive control model that considers fish population density and its current growth rate, providing new ideas for fishing strategies. First, we established a phytoplankton-fish model with state-impulse feedback control based on fish density and rate of change. Secondly, the complex phase sets and impulse sets of the model are divided into three cases, then the Poincaré map of the model is defined and its complex dynamic properties are deeply studied. Furthermore, some necessary and sufficient conditions for the global stability of the fixed point (order-1 limit cycle) have been provided even for the Poincaré map. The existence conditions for periodic solutions of order-k(k≥2) are discussed, and the influence of dynamic thresholds on system dynamics is shown. Dynamic thresholds depend on fish density and rate of change, i.e., the form of control employed is more in line with the evolution of biological populations than in earlier studies. The analytical method presented in this paper also plays an important role in analyzing impulse models with complex phase sets or impulse sets.

The value of NIPT combined with serum cell-free DNA, estriol, AFP, and b-HCG levels in the recognition of trisomy 21 and 18 in the second trimester.

Background: This study aimed to evaluate the clinical application value of noninvasive prenatal testing from DNA (NIPT) and serum screening for screening in detecting fetal trisomy 21 and 18. Methods: As a retrospective analysis, we collected data from 1383 women (singleton pregnancy) who underwent serum screening and noninvasive prenatal testing from DNA (NIPT) in our department from May 2015 to September 2017 and calculated the diagnostic value of the two methods.

[The investigations on the relationship between the birth weight of fetus and the P70 S6K as well as mechanism insulin regulate the birth weight of fetus].

OBJECTIVES: To investigate the relationship between the birth weight of fetus and the P(70)S6K from ribosome in cells of placental tissues and investigate whether insulin can affect the P(70)S6K by the PI3K/AKT/mTOR (P(70)S6K) signaling pathway in the cells of the placental tissues and more regulate the birth weight of fetus. METHODS: (1) 60 cases of mature placental tissues after uterine-incision delivery without complications in the gestational period were selected as the investigated subjects, they were divided into three groups according to their birth weights. group 1. the weigh of the fetus > or = 4000 g, group 2. 3000 g < or = the weight of the fetus < 4000 g, group 3. the weight of the fetus < 3000 g, (2) 10 cases of mature placental tissues and 20 cases of villus in the early pregnant the fetus that were divided into insulin group, rapamycin group and control group according to stimulating factors. investigations on the insulin affection activities of P(70)S6K were carried out by immunoprecipitation, incorporation of [r-(32)P]ATP, tissue cell culture, Western blotting. RESULTS: (1) P(70)S6K activities in mature placental tissues (2546 +/- 357), (2333 +/- 318), (2111 +/- 315) cpm/mg, there were significant statistical differences in the comparison every two groups. (2) The P(70)S6K activities in the placenta from the insulin stimulation group was significantly elevated, the P(70)S6K activities in the placenta from the rapamycin stimulation group was significantly declined, there were statistical significance when each was compared with control group (P < 0.01). (3) P(70)S6K activities in the nutrient cells of earlier pregnant period and protein expression will be elevated under insulin stimulating. However, that would be declined under rapamycin stimulating, it was statistical significant when each group compared with the control group (P < 0.01). CONCLUSION: The activities of P(70)S6K increased with the increase in the birth weight of the fetus, there was certain relationship between the activities of P(70)S6K in the placental tissues and the birth weight of the fetus and Insulin can regulate the activities of P(70)S6K in the placenta and earlier nutrient cells.

Efficacy and safety of misoprostol compared with the dinoprostone for labor induction at term: a meta-analysis.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of intravaginal misoprostol and the dinoprostone vaginal insert for labor induction at term. METHOD: PubMed, EMBASE, MEDLINE, CNKI, EBSCO and the Cochrane Library were searched for articles published in English language from 2000 to 2014, Using the keywords misoprostol, dinoprostone, labor induction. RESULTS: Eight of 436 studies (1669 women) identified met the criteria for meta-analysis. We assigned a quality rating to each included article. The use of misoprostol showed less oxytocin augmentation when compared with dinoprostone (RR = 0.78, 95% CI = 0.67-0.90). There was no difference in the risk of tachysystole (RR = 1.18, 95% CI = 0.78-1.79), uterine hyperstimulation (RR = 1.24, 95% CI = 0.75-2.06), vaginal delivery within 24 h (RR = 1.10, 95% CI = 1.00-1.20), cesarean delivery (RR = 0.84, 95% CI = 0.56-1.24), Neonatal Intensive Care Unit admission (RR = 0.86, 95% CI = 0.58-1.28), Apgar scores <7 in 5 min (RR = 1.18, 95% CI = 0.39-3.63) between misoprostol and dinoprostone. CONCLUSION: Misoprostol compared with dinoprostone appears to show less oxytocin augmentation for labor induction at term. The other outcomes of both drugs were similar. However, these findings were based on small-scale trials. Further studies assessing the effectiveness and safety of misoprostol and dinoprostone in selected groups of patients are warranted.

Which is the safer method of labor induction for oligohydramnios women? Transcervical double balloon catheter or dinoprostone vaginal insert.

OBJECTIVE: To compare the effectiveness and safety of two cervical ripening methods in term primiparous women with unfavorable cervices and oligohydramnios. METHODS: Women (126 cases) with oligohydramnios [amniotic fluid index (AFI) ≤5 cm] and a low Bishop Score (≤6) were assigned randomly to use double balloon catheter (mechanical method group, 67 cases) or dinoprostone 10 mg controlled-release vaginal insert (pharmacological method group, 59 cases) for induction of labor. The study's primary outcome was caesarean section rate (CSR). The secondary outcome measures included maternal and neonatal morbidity, an incremental changes in Bishop Score, and intrapartum interventions. RESULTS: There was no significant difference between the mechanical method group and the pharmacological method group in CSR and change in Bishop Score. Tacysystole, non-reassuring fetal heart patterns, and cases of newborn umbilical-cord arterial blood pH<7.1 were significantly lower with the mechanical method compared with the pharmacological method (p < 0.05). More patients needed additional intervention in the mechanical method group. CONCLUSIONS: Both methods resulted in a similar CSR. Double balloon catheter resulted in fewer labor complications, but more frequent use of oxytocin and amniotomy. Compared with dinoprostone vaginal insert, double balloon catheter use may be less problematic in women with oligohydramnios.