Problem
This study aimed to identify subsets of regulatory T cells (Tregs) associated with ovarian aging and determine whether they can be used as markers of reproductive aging.
Method
This ...prospective cohort study was conducted among women of reproductive age. Basic physiological characteristics, reproductive hormones, Treg cell subsets, and correlations between these parameters were assessed. The POSEIDON criteria was used to identify women with low reproductive potential.
Results
The percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells significantly increased with age. Women between 40 and 49 years had significantly higher percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells than those at 20–29, 30–34, and 35–39 years old. Age positively correlated with FSH levels and the percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells, but inversely correlated with antral follicle count (AFC) and AMH levels. Interestingly, a positive correlation was found between the percentages of HLA‐DR+ CD45RAˉ Tregs and FSH levels, whereas an inverse correlation was found between those of HLA‐DR+ CD45RAˉ Tregs and AFC or AMH levels. Furthermore, a significant positive correlation was observed between the percentages of CD28ˉ Treg‐like cells and AFC. Based on POSEIDON criteria, women with the percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells above reference value ranges were assigned to the low prognosis groups.
Conclusion
These findings suggest that HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells can be used as immunologic markers of reproductive aging, which helps clinicians identify women with low reproductive potential and establish individualized therapeutic strategies.
During pregnancy, cell senescence at the maternal–fetal interface is required for maternal well-being, placental development, and fetal growth. However, recent reports have shown that aberrant cell ...senescence is associated with multiple pregnancy-associated abnormalities, such as preeclampsia, fetal growth restrictions, recurrent pregnancy loss, and preterm birth. Therefore, the role and impact of cell senescence during pregnancy requires further comprehension. In this review, we discuss the principal role of cell senescence at the maternal–fetal interface, emphasizing its “bright side” during decidualization, placentation, and parturition. In addition, we highlight the impact of its deregulation and how this “dark side” promotes pregnancy-associated abnormalities. Furthermore, we discuss novel and less invasive therapeutic practices associated with the modulation of cell senescence during pregnancy. Summary Sentence An overview of the recent discoveries on the physiology role of cell senescence in successful pregnancies and pathology role of excessive cell senescence in complicated pregnancy. Graphical Abstract
Coronavirus disease 2019 (COVID-19) is an infectious disease affecting multiple systems and organs, including the reproductive system. SARS-CoV-2, the virus that causes COVID-19, can damage ...reproductive organs through direct (angiotensin converting enzyme-2, ACE-2) and indirect mechanisms. The immune system plays an essential role in the homeostasis and function of the male and female reproductive systems. Therefore, an altered immune response related to infectious and inflammatory diseases can affect reproductive function and fertility in both males and females. This narrative review discussed the dysregulation of innate and adaptive systems induced by SARS-CoV-2 infection. We reviewed the evidence showing that this altered immune response in COVID-19 patients is the major indirect mechanism leading to adverse reproduction outcomes in these patients. We summarized studies reporting the long-term effect of SARS-CoV-2 infection on women's reproductive function and proposed the chronic inflammation and chronic autoimmunity characterizing long COVID as potential underlying mechanisms. Further studies are needed to clarify the role of autoimmunity and chronic inflammation (long COVID) in altered female reproduction function in COVID-19.
Objective: To explore peripheral blood cell variations in hepatic cirrhosis portal hypertension patients with hypersplenism. Methods: Clinical data of 322 hypersplenism patients with decreased ...peripheral blood cells, admitted with cirrhotic portal hypertension, was retrospectively studied over the last 17 years. Results: In 64% (206/322) of patients, more than 2 kinds of blood cell were decreased, including 89 cases of pancytopenia (43.2%), 52 cases of WBC + PLT decrease (25.2%), 29 cases of RBC + PLT decrease (14.1%), and 36 cases of WBC + RBC decrease (17.5%); in 36% (116/322) of patients, single type blood cell decrease occurred, including 31 cases of PLT decrease (26.7%), 29 cases of WBC decrease (25%) and 56 cases of RBC decrease (48.3%). Of 227 routine bone marrow examinations, bone marrow hyperplasia was observed in 118 cases (52.0%), the remainder showed no hyperplasia. For the distinct scope and extent of peripheralblood cell decreases, preoperative blood component transfusions were carried out, then treated by surgery, after whole group splenectomy, the peripheral blood cell count was significantly higher ( P <0.05). Conclusions: Of portal hypertensive patients with splenomegaly and hypersplenism, 64% have simultaneous decrease in various blood cells, 36% have decrease in single type blood cells, 52% of patients have bone marrow hyperplasia. A splenectomy can significantly increase the reduction of peripheral blood cells.
To investigate the appropriate cutoff point of CA19-9 for prognosis and other potential prognostic factors that may affect survival of patients with hilar cholangiocarcinoma (HC) after radical ...surgery. 168 patients who had undergone radical surgery for hilar cholangiocarcinoma and resultant macroscopic curative resection (R0 and R1) were discreetly selected for analyses. Categorized versions were used in univariate model to determine the appropriate cutoff point of CA19-9. CA19-9 and other clinicopathologic factors were analyzed for influence on survival by univariate and multivariate methods. The strongest univariate predictor among the categorized preoperative CA19-9 measures was CA19-9 less than 150 IU/L (P = 0.000). In univariate analysis, tumor size, Bismuth-Corlette classification, portal vein invasion, Lymph node metastasis, resection margin and preoperative CA19-9 levels were identified as significant prognostic factors. In multivariable analysis, lymph node metastasis, resection margin and preoperative CA19-9 levels were independent prognostic factors. our results demonstrated that preoperative CA19-9 levels was also an independent prognostic factor for hilar cholangiocarcinoma, and the most discriminative cutoff point of CA19-9 for prognosis proved to be at 150 U/ml.
AIM: Hepatic cytochrome P450 isoenzymes constitute a superfamily of hemoproteins that play a major role in the metabolism of endogenous compounds and in the detoxification of xenobiotic molecules. ...P450 3A4 is one of the most important forms in human being, and mediates the metabolism of around 70 % of therapeutic drugs and endogenous compounds. Propofol, a widely used intravenous anesthetic drug, is known to inhibit cytochrome P450 activities in isolated rat hepatocytes. The goal of this study was to evaluate the potential efficacy of propofol on P450 3A4 in a dose-dependent manner to understand its drugdrug interaction.METHODS: Hepatocytes were isolated from liver specimens from hepatic angioma patients undergone hepatic surgery.Primary incubated hepatocytes were treated with 0, 0.01,0.05, 0.1, 0.5, and 1.0 mM propofol for 24 hours. P450 3A4 activity was measured with Nash's colorimetry. The protein expression was assessed by Western blot analysis.RESULTS: A dose-dependent inhibitory effect of propofol was observed in cytochrome P450 3A4 activity. A minimal dosage of pmpofol (0.01 mM) induced a significant inhibition of P450 3A4 activity, although its regular dosages (0.01-0.1mM) showed no inhibitory effect on the cellular protein expression of P450 3A4.CONCLUSION: Propofol may be a potential CYP3A4 inhibitor as this anesthetic can inhibit isoenzyme activity significantly and reduce the metabolic rate of CYP3A4 substrates. This inhibition occurs at post-expression level, and concentration of propofol used clinically does not affect CYP3A4 protein expression, propofol may thus induce drug interaction of cytochmme P450 3A4 activity at the dosage used clinically.
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Boron nuclei in cosmic rays (CRs) are believed to be mainly produced by the fragmentation of heavier nuclei, such as carbon and oxygen, via collisions with the interstellar matter. ...Therefore, the boron-to-carbon flux ratio (B/C) and the boron-to-oxygen flux ratio (B/O) are very essential probes of the CR propagation. The energy dependence of the B/C ratio from previous balloon-borne and space-based experiments can be well described by a single power-law up to about 1 TeV/n within uncertainties. This work reports direct measurements of B/C and B/O in the energy range from 10 GeV/n to 5.6 TeV/n with 6 years of data collected by the Dark Matter Particle Explorer, with high statistics and well controlled systematic uncertainties. The energy dependence of both the B/C and B/O ratios can be well fitted by a broken power-law model rather than a single power-law model, suggesting the existence in both flux ratios of a spectral hardening at about 100 GeV/n. The significance of the break is about 5.6σ and 6.9σ for the GEANT4 simulation, and 4.4σ and 6.9σ for the alternative FLUKA simulation, for B/C and B/O, respectively. These results deviate from the predictions of conventional turbulence theories of the interstellar medium (ISM), which point toward a change of turbulence properties of the ISM at different scales or novel propagation effects of CRs, and should be properly incorporated in the indirect detection of dark matter via anti-matter particles.
Laser-induced breakdown spectroscopy （LIBS） is an emerging analytical spectroscopy technique. Thisreview presents the main recent developments in China regarding the implementation of LIBS for ...coalanalysis. The paper mainly focuses on the progress of the past few years in the fundamentals, datapretreatment, calibration model, and experimental issues of LIBS and its application to coal analysis.Many important domestic studies focusing on coal quality analysis have been conducted.
AIM:To report the outcome of patients with ruptured hepatocellular carcinoma(HCC)treated at a single center during a 5-year period.METHODS:We retrospectively analyzed 32 patients who presented with ...ruptured HCC at Shandong Provincial Hospital Affiliated to Shandong University between2008 and 2013.RESULTS:The mean age of the patients was 53 years(range 39-71 years).Of these patients,22 received surgical management,10 underwent transarterial embolization(TAE)or transarterial chemoembolization(TACE),and 12 received sorafenib after surgery,TAE or TACE.Cumulative survival rates at 4,8 and 12 mo were72.9%,50.0%and 33.3%,respectively,in the surgery only group and were 90.0%,80.6%and 64.1%,respectively,in the surgery plus sorafenib group.Cumulative survival rates at 4,8 and 12 mo were 68.4%,43.6%and 19.4%,respectively,in the surgery only or TAE/TACE only groups,and were 91.7%,75.0%and 60.2%,respectively,in the sorafenib combination groups(P=0.04).No unexpected side effects due to sorafenib were observed.The most common side effect was hand-foot skin reaction.To date,5 patients have died.Median follow-up from the start of sorafenib therapy for the remaining 7 patients is 12.7 mo(range5.8-32.2 mo).CONCLUSION:Sorafenib can be used in patients with ruptured HCC as it has interesting activity and is well tolerated;dose adjustment is generally not required.However,a larger prospective study is necessary to determine the efficacy of sorafenib in this group of patients.
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