Hypothyroidism in the first trimester of pregnancy (T1) has great adverse effects on mothers and foetuses. However, few studies have investigated the influence on postpartum thyroid dysfunction. This ...study aimed to evaluate their long-term effect on postpartum thyroid function within one year after delivery.
In total, 151 women were recruited from 1496 participants and were classified as newly diagnosed subclinical hypothyroidism (SCH) in T1 (ND-SCH, n=50), previously known SCH before pregnancy (PK-SCH, n=51) and previously known overt hypothyroidism (PK-OH, n=50). Their thyroid functions were dynamically monitored from pre-conception to one-year postpartum.
During pregnancy, the first thyroid functions' test time in T1 were 5-8 gestational weeks. After delivery, the prevalence of postpartum thyroiditis (PPT) was comparable in women with previously known and newly diagnosed hypothyroidism ND-SCH 62.0%
PK-SCH 64.7%
PK-OH 64.0%, P=0.96. For the ND-SCH group, PPT was significantly related with thyroid-stimulating hormone (TSH) >4.0 mU/L occurring at <8 gestational weeks OR=8.06, 95% CI, 2.08-31.29 and TSH levels outside 1.0-2.5 mU/L near childbirth OR=3.73, 95% CI, 1.04-13.41. For patients with known hypothyroidism before pregnancy (PK-SCH and PK-OH), TSH>2.5 mU/L in T1 OR=3.55, 95% CI, 1.43-8.81 and TPOAb≥300 μIU/mL OR=6.58, 95% CI, 2.05-21.12 were associated with PPT. Regardless of whether SCH was diagnosed before pregnancy or in T1, the levothyroxine (LT4) treatment was discontinued at delivery. More than 50% of the patients had to face the hypothyroidism phase of postpartum and restarted LT4 treatment in the first-year follow-up. The logistic regression analysis revealed that TSH elevation occurring at <8 gestational weeks OR=2.48, 95% CI, 1.09-5.6, TSH levels outside 1.0-2.5 mU/L near childbirth OR=3.42, 95% CI, 1.45-8.05, and TPOAb≥300 μIU/mL OR=6.59, 95% CI, 1.79-24.30 were the risk factors.
TSH elevation at <8 gestational weeks was associated with PPT after delivery in women with known and newly diagnosed hypothyroidism. Especially for SCH patients who stopped LT4 treatment at delivery, unsatisfactory TSH level at <8 gestational weeks and near childbirth, TPOAb≥300 μIU/mL were the risk factors for LT4 retreatment in one-year postpartum.
APOBEC family play an important role in cancer mutagenesis and tumor development. The role of APOBEC family in lung adenocarcinoma (LUAD) has not been studied comprehensively.
The expression data of ...pan-cancer as well as LUAD was obtained from public databases. The expression level of APOBEC family genes was analyzed in different normal and cancer tissues. APOBEC mutagenesis enrichment score (AMES) was utilized to evaluate the APOBEC-induced mutations and the relation of APOBEC with genomic instability. Gene set enrichment analysis was used to identify differentially enriched pathways. Univariate Cox regression and Lasso regression were applied to screen key prognostic genes. The immune cell infiltration was estimated by CIBERSORT. RT-qPCR assay, CCK-8 and Transwell assay were conducted to explore gene expression and lung cancer cell invasion.
Cancer tissues had significantly altered expression of APOBEC family genes and the expression patterns of APOBEC family were different in different cancer types. APOBEC3B was the most aberrantly expressed in most cancer types. In LUAD, we observed a significantly positive correlation of AMES with intratumor heterogeneity (ITH), tumor neoantigen burden (TNB), and tumor mutation burden (TMB). High AMES group had high mutation counts of DNA damage repair pathways, and high enrichment of cell cycle and DNA repair pathways. We identified four prognostic genes (LYPD3, ANLN, MUC5B, and FOSL1) based on AMES, and constructed an AMES-related gene signature. The expressions of four genes were enhanced and accelerated the invasion ability and viability of lung cancer cells. Furthermore, we found that high group increased oxidative stress level.
APOBEC family was associated with genomic instability, DNA damage-related pathways, and cell cycle in LUAD. The AMES-related gene signature had a great potential to indicate the prognosis and guide immunotherapy/chemotherapy for patients suffering from LUAD.
This work aims to study the construction of reverse aspirin-loaded micelles prepared from amphiphilic PEG-PLA-SA triblock copolymers and the optimization of the preparation process. Using ...polyethylene glycol (PEG) as the initiator, ring-opening polymerization of L-lactide (L-LA) was used to prepare PEG-PLA diblock copolymers. Final product PEG-PLA-SA triblock copolymers were prepared by the reaction of stearic acid (SA) and PEG-PLA catalyzed by 4-dimethylaminopyridine (DMAP) and N,N'-Dicyclohexylcarbodiimide (DCC). Fourier transform infrared spectrometer (FT-IR) was used to characterize the product structure. PEG-PLA-SA triblock copolymers self-assembled in toluene/ethanol/water system to form reverse micelles, which could encapsulate aspirin into a hydrophilic core. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to determine the size and morphology of reverse micelles. The results showed that the reverse micelles are spherical, with a particle size of less than 70 nm. Response surface analysis method was applied to optimize the preparation process of PEG-PLA-SA. In vitro drug release was achieved by embedding reverse aspirin-loaded micelles in the biocompatible membrane in phosphate buffer saline (PBS) at 37°C. In the first 8 h, the drug release rate of the triblock copolymers was slower than that of the diblock copolymers. After 8 h, the drug release rate of both tended to be flat. The stability of aspirin-loaded reverse micelles was studied through accelerated test. These results indicate that reverse micelle PEG-PLA-SA may be a promising carrier for hydrophilic drugs like aspirin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aim: To systematically evaluate the effect of Gandankang (GDK) aqueous extract in alleviating acute and chronic liver injury. Forty-one chemical compounds were identified by ultra-high performance ...liquid chromatography-linear trap quadrupole-orbitrap-tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS) from GDK. All dosages of GDK and Biphenyl diester (BD) improved CCl4-induced acute and chronic liver injury. GDK curbed liver fibrosis and blocked the NF-κB pathway to effectively inhibit the hepatic inflammatory response. Additionally, GDK treatment reduced the abundance of Phascolarctobacterium, Turicibacter, Clostridium_xlva, Atoprostipes, and Eubacterium, in comparison with those in the CCl4 mice and elevated the abundance of Megamonas and Clostridium_IV as evident from 16S rDNA sequencing. Correlation analysis showed that the abundance of Eubacterium and Phascolarctobacterium was positively correlated with inflammation, fibrosis, and oxidation indexes. This indicates that GDK ameliorates chronic liver injury by mitigating fibrosis and inflammation. Nrf2 pathway is the key target of GDK in inhibiting liver inflammation and ferroptosis. Eubacterium and Phascolarctobacterium played a vital role in attenuating liver fibrosis.
Mass spectrometry technology is becoming an important tool for clinical analysis due to its high specificity, high sensitivity and high multi-component detection capability. The current applications ...of this technology are mainly in liquid chromatography-tandem mass spectrometry (LC-MS/MS), matrix-assisted laser desorptionionization time-of-flight mass spectrometry (MALDI-TOF-MS), inductively coupled plasma mass spectrometry (ICP-MS), gas chromatography-mass spectrometry (GC-MS) and the related in vitro diagnostic kits. At present, the number of medical device (MD) based on mass spectrometry technology is growing rapidly, especially the number of LC-MS/MS and MALDI-TOF-MS registered MD products, and the standardization of relevant product quality requirements is also being effectively carried out. In general, clinical mass spectrometry equipment is still mainly imported, and the equipment price is relatively high. The development of mass spectrometry kits is mainly based on imported platforms, and domestic equ
Despite improvements in disease diagnosis, treatment, and prognosis, breast cancer is still a leading cause of cancer death for women. Compelling evidence suggests that targeting cancer stem cells ...(CSCs) have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy. In the present study, we aimed to study the effects of T cells and a critical anti-tumor cytokine, interferon-gamma (IFN-γ), on breast cancer stem cells.
BALB/c mice and BALB/c nude mice were subcutaneously injected with 4T1 tumor cells. Tumor growth and pulmonary metastasis were assessed. ALDEFLOUR™ assays were performed to identify aldehyde dehydrogenasebright (ALDHbr) tumor cells. ALDHbr cells as well as T cells from tumor-bearing BALB/c mice were analyzed using flow cytometry. The effects of CD8+ T cells on ALDHbr tumor cells were assessed in vitro and in vivo. The expression profiles of ALDHbr and ALDHdim 4T1 tumor cells were determined. The levels of plasma IFN-γ were measured by enzyme-linked immunosorbent assay, and their associations with the percentages of ALDHbr tumor cells were evaluated. The effects of IFN-γ on ALDH expression and the malignancy of 4T1 tumor cells were analyzed in vitro.
There were fewer metastatic nodules in tumor-bearing BALB/c mice than those in tumor-bearing BALB/c nude mice (25.40 vs. 54.67, P < 0.050). CD8+ T cells decreased the percentages of ALDHbr 4T1 tumor cells in vitro (control vs. effector to target ratio of 1:1, 10.15% vs. 5.76%, P < 0.050) and in vivo (control vs. CD8+ T cell depletion, 10.15% vs. 21.75%, P < 0.001). The functions of upregulated genes in ALDHbr 4T1 tumor cells were enriched in the pathway of response to IFN-γ. The levels of plasma IFN-γ decreased gradually in tumor-bearing BALB/c mice, while the percentages of ALDHbr tumor cells in primary tumors increased. IFN-γ at a concentration of 26.68 ng/mL decreased the percentages of ALDHbr 4T1 tumor cells (22.88% vs. 9.88%, P < 0.050) and the protein levels of aldehyde dehydrogenase 1 family member A1 in 4T1 tumor cells (0.86 vs. 0.49, P < 0.050) and inhibited the abilities of sphere formation (sphere diameter <200 μm, 159.50 vs. 72.0; ≥200 μm, 127.0 vs. 59.0; both P < 0.050) and invasion (89.67 vs. 67.67, P < 0.001) of 4T1 tumor cells.
CD8+ T cells and IFN-γ decreased CSC numbers in a 4T1 mouse model of breast cancer. The application of IFN-γ may be a potential strategy for reducing CSCs in breast cancer.
Previous studies indicate the effects of thyroid dysfunction on adverse obstetric outcomes and fetal neurodevelopment, of which the results on gestational anemia are controversial. Here, we evaluated ...the influence of thyroid dysfunction on gestational anemia via published epidemiological articles and a new prospective study conducted by our team, respectively.
We searched studies on the PubMed, Embase, MEDLINE, and Cochrane databases as of November 2019, and conducted a prospective study in which participants underwent thyroid function and blood routine testing throughout pregnancy.
The meta-analysis showed that pregnancies with overt hypothyroidism OH; odds ratio (OR) = 3.74, 95% confidence interval (CI): 1.95-7.15 or that were thyroid peroxidase antibody (TPOAb)-positive (OR = 1.97, 95%CI: 1.19-3.26) had increased anemia risk, but similar results were not found in pregnancies with subclinical hypothyroidism (SCH) and hyperthyroidism. In the prospective study from our new data, the hypothyroid group had significant reductions in hemoglobin (Hb) (
= 0.048) and increased anemia risk (OR = 6.384, 95%CI: 2.498-16.311) during the second half of pregnancy. From the first to second half of pregnancy, the longitudinal reductions in Hb, erythrocyte (RBC), and hematocrit (Hct) levels were significantly increased in hypothyroid group.
Our meta-analysis indicates that untreated OH or TPOAb-positive pregnant women have increased risk of anemia. In addition, our new data showed that treated hypothyroidism is also a risk factor for anemia in the second half of pregnancy rather than in the first half. The results may guide strengthening of Hb monitoring in pregnancies with thyroid dysfunction.
Background and Aims
Leukocytospermia (LCS) is a known cause of male infertility. However, the relationship between seminal leukocytes and semen quality among infertile couples remains controversial. ...This study aims to investigate the association between semen quality and LCS in male partners of infertile couples.
Methods
Semen samples were collected from 512 men who asked for a fertility evaluation in a reproductive center in China. Seminal leukocytes were counted following peroxidase staining with benzidine. Other semen parameters were compared in subfertile men with and without LCS.
Results
Poor semen quality (e.g., low semen volume, sperm concentration, and sperm progressive/total motility) was observed among men with LCS compared to those without LCS. Men with LCS had a higher risk of low sperm progressive motility (OR = 0.99, 95% CI = 0.98−0.99, p = 0.02) and total motility (OR = 0.99, 95% CI = 0.98−0.99, p = 0.02), even after adjustment for potential confounders (both OR = 0.99, 95% CI = 0.98−0.99, p = 0.03). Lower sperm viability was observed in LCS from male partners of secondary couples, while no significant difference in semen parameters was found between men with and without LCS in male partners of primary infertile couples. Low sperm motility and viability were associated with LCS in men from secondary infertile couples after adjusting for confounders (OR = 0.97, 95% CI = 0.95−0.99, p = 0.04; OR = 0.94, 95% CI = 0.89−0.99, p = 0.04, respectively).
Conclusions
Our findings indicate that a higher risk of abnormal semen parameters was correlated with an increased number of leukocytes in men from secondary infertile couples.
Large-eddy simulation (LES) of CH
4
-air low-swirl flame was carried out in a multi-nozzle combustor with two burner configurations by using a premixed flamelet model. The multi-nozzle burner ...includes a co-swirling array where all five nozzles act in the same direction and a counter-swirling array where the center nozzle is in the opposite swirling direction to the outer nozzles. LES results are in good agreement with OH-planar laser-induced florescence data in terms of OH concentrations and combustion progress variables. Numerical results show that the flow of each nozzle is constant before merging. The neighboring flows interact with each other and generate a highvelocity zone with intensive turbulence. The kinetic energy in the interacting region for the co-swirling array is larger than that for the counter-swirling array. After neighboring flow combining, the flow develops into a unified swirling motion similar to a single swirling flow for the co-swirling array, whereas the flow maintains the individual swirling structures for the counter-swirling arrangement. However, the swirling array exerts minimal effect on multi-nozzle combustion in terms of the temperature distributions and combustion progress of premixed low-swirl multi-nozzle flames.
The present study was conducted to evaluate the effect of dietary folic acid on the growth performance, intestinal morphology, and intestinal epithelial cells renewal in post-weaning piglets. ...Twenty-eight piglets (weaned at day 21, initial body weight of 6.73 ± 0.62 kg) were randomly allotted to 4 treatments with 7 pens per diet and 1 piglet per pen. The piglets were fed the same antibiotic-free and zinc oxide-free basal diets supplemented with folic acid at 0, 3, 9, and 18 mg/kg for 14 days. The results showed that dietary supplementation with folic acid increased villus height (VH) (P = 0.003; linear, P = 0.001), VH-to-crypt depth (VH:CD) ratio (P = 0.002; linear, P = 0.001), villus surface area (VSA) (P = 0.026; linear, P = 0.010). The analyzed parameters ADG, serum urea nitrogen (BUN) content, VH, VSA, and serum folate (SF) concentration responded linearly to the dietary folic acid concentration when the dietary folic acid concentration was below 4.42, 5.26, 4.79, 3.47, and 3.53 mg/kg respectively (R2 = 0.995, 0.995, 0.999, 0.999, 0.872, P = 0.09, 0.07, 0.09, 0.09, 0.36, respectively), as assessed by a two-linear broken-line regression. Above these breakpoints, the response of ADG, VH, VSA, and SF plateaued in response to changes in dietary folic acid concentration. Moreover, dietary supplementation with folic acid significantly increased the lactase (P = 0.001; linear, P = 0.001) and sucrase activities (P = 0.021; linear, P = 0.010) in the jejunal mucosa of weaned piglets. The mRNA expression of solute carrier family 6 member 19 (SLC6a19), solute carrier family 1 member 1 (SLC7a1), tumor necrosis factor-α (TNF-α), the number of Ki67 positive cells, and cell shedding rate had a significant linear contrast (P = 0.023, 0.021, 0.038, 0.049, and 0.008, respectively) in dietary folic acid groups. In conclusion, our results indicate that folic acid supplementation can improve the growth performance and intestinal morphology of weaned piglets by maintaining the balance of epithelial cell renewal.
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