Background
Long non-coding RNAs (lncRNAs) are well established to have an important role in cancer. The goal of this research was to investigate the prognostic usefulness of putative immune-related ...lncRNAs in hepatocellular carcinoma (HCC).
Methods
The developed lncRNA signature was validated using 343 HCC patients from The Cancer Genome Atlas (TCGA) and 81 samples from Gene Expression Omnibus (GEO). Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were used to analyze immune-related lncRNAs for HCC prognosis. Patients in the low-risk group survived substantially longer than those in the high-risk group (
P
< 0.05). The discovered signal might be a useful prognostic factor for predicting patient survival. Overall survival predicted some clinical net improvements, according to the nomogram. Numerous enrichment approaches (including gene set enrichment analysis) were utilized to investigate the underlying mechanisms.
Results
Drug metabolism, mTOR, and p53 signaling pathways were associated with high-risk groups. When the expression of lncRNA PRRT3-AS1 was silenced in HepG2 cells, the proliferation, migration, and invasion abilities of HepG2 cells were decreased, and apoptosis was enhanced. In the supernatant from HepG2 cells with PRRT3-AS1 knockdown, the anti-inflammatory factors IL-10 and TGF-1 were induced, whereas the pro-inflammatory factors IL-1β, TNF-α, and IL-6 were reduced (
P
< 0.05). After PRRT3-AS1 knockdown, the protein expression of CD24, THY1, LYN, CD47, and TRAF2 in HepG2 cells was attenuated (
P
< 0.05).
Conclusion
The discovery of five immune-related lncRNA signatures has significant therapeutic significance for predicting patient prognosis and directing personalized treatment for patients with HCC, which requires additional prospective confirmation.
Objective
Somatic variants in the ubiquitin‐specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and ...USP8 status in a single centre.
Design, patients and measurements
We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow‐up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed.
Results
Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type WT, p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47‐ vs. 24‐year‐olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long‐term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence‐free survival presented a tendency to be shorter in USP8‐mutated individuals (76.7 vs. 109.2 months, p = .068).
Conclusions
Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long‐term follow‐up revealed a tendency toward shorter recurrence‐free survival in USP8‐mutant patients.
Background To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the DELAZ value of weight at discharge. Methods The ...clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of DELAZ value of weight at discharge < -1.28. Results This study included 133 eligible VPI with SGA. Following the criterion of DELAZ value, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-min Apgar score, and the proportion of male infants in the EUGR group were lower (P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group (P < 0.05). In the EUGR group, several factors exhibited higher values (P < 0.05), including the initiation of enteral feeding, the volume of milk supplemented with human milk fortifier (HMF), the duration to achieve complete fortification, the cumulative duration of fasting, the duration to achieve full enteral feeding, the length of parenteral nutrition (PN), the number of days required to attain the desired total calorie intake and oral calorie intake, as well as the age at which birth weight was regained. The average weight growth velocity (GV) was significantly lower in the EUGR group (P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) stagegreater than or equal to 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were higher (P < 0.05). Multivariate logistic regression analysis showed that birth weight, male, and GV were the protective factors, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC stage greater than or equal to2 were the independent risk factors. Conclusion SGA in VPI can reflect the occurrence of EUGR more accurately by using the DELAZ value of weight at discharge. Enhancing enteral nutrition support, achieving prompt and complete fortification of breast milk, promoting greater GV, reducing the duration of birth weight recovery, and minimizing the risk of NEC can contribute to a decreased occurrence of EUGR. Trial registration CHICTR, ChiCTR1900023418. Registered 26/05/2019, Keywords: Extrauterine growth retardation, Extremely premature infants, GV, Nutrition, Small for gestational age, Z score
The hostile environment of an injured spinal cord makes it challenging to achieve higher viability in a grafted tissue-engineered neural network used to reconstruct the spinal cord circuit. Here, we ...investigate whether cell survival and synaptic transmission within an NT-3 and TRKC gene-overexpressing neural stem cell-derived neural network scaffold (NN) transplanted into transected spinal cord could be promoted by electroacupuncture (EA) through improving the microenvironment. Our results showed that EA facilitated the cell survival, neuronal differentiation, and synapse formation of a transplanted NN. Pseudorabies virus tracing demonstrated that EA strengthened synaptic integration of the transplanted NN with the host neural circuit. The combination therapy also promoted axonal regeneration, spinal conductivity, and functional recovery. The findings highlight EA as a potential and safe supplementary therapeutic strategy to reinforce the survival and synaptogenesis of a transplanted NN as a neuronal relay to bridge the two severed ends of an injured spinal cord.
•EA promotes the survival and synapse formation of NSC-derived neurons in grafted NN•EA strengthens synaptic integration of grafted NN with the spinal cord neural circuit•EA enhances NT-3 level and activates NT-3/TRKC/AKT pathway in the injury/graft site•The combination therapy increases axonal regeneration and spinal functional recovery
In this article, Y.S. Zeng, Y. Ding, and colleagues show that EA treatment can reinforce the survival, neuronal differentiation, and synaptic connections of donor neurons in injured spinal cord by activating the NT-3/TRKC/AKT pathway. Moreover, the combinational therapy fosters host axonal regeneration into the injury/graft site to rebuild the synaptic connections with grafted NN, and improves nerve conduction of the spinal cord as well as locomotor function of paralyzed hindlimbs.
Purpose
This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5‐fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two‐group, nonrandomized, ...multicenter, phase II trial in patients with initially technically unresectable colorectal liver‐limited metastases (CLM) and BRAF/RAS wild‐type.
Patients and Methods
Patients were enrolled to receive cetuximab (500 mg/m2) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, folinic acid 400 mg/m2, 5‐fluorouracil 2,800 mg/m2 46‐hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety.
Results
Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval CI, 9.1%–48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%–36.4%; p = .010) compared with those in control group. Progression‐free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups.
Conclusion
Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM.
Implications for Practice
This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver‐limited metastases and BRAF/RAS wild‐type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression‐free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver‐limited metastasis.
The FOCULM study was designed to evaluate whether cetuximab would improve the efficacy of a modified FOLFOXIRI regimen as conversion therapy in patients with RAS/BRAF wild‐type unresectable colorectal liver‐limited metastases. Results are reported here.
Embryo implantation into the maternal uterus is a crucial step for the successful establishment of mammalian pregnancy. Following the attachment of embryo to the uterine luminal epithelium, uterine ...stromal cells undergo steroid hormone-dependent decidualization, which is characterized by stromal cell proliferation and differentiation. The mechanisms underlying steroid hormone-induced stromal cell proliferation and differentiation during decidualization are still poorly understood. Ribonucleotide reductase, consisting of two subunits (RRM1 and RRM2), is a rate-limiting enzyme in deoxynucleotide production for DNA synthesis and plays an important role in cell proliferation and tumorgenicity. Based on our microarray analysis, Rrm2 expression was significantly higher at implantation sites compared with interimplantation sites in mouse uterus. However, the expression, regulation, and function of RRM2 in mouse uterus during embryo implantation and decidualization are still unknown. Here we show that although both RRM1 and RRM2 expression are markedly induced in mouse uterine stromal cells undergoing decidualization, only RRM2 is regulated by progesterone, a key regulator of decidualization. Further studies showed that the induction of progesterone on RRM2 expression in stromal cells is mediated by the AKT/c-MYC pathway. RRM2 can also be induced by replication stress and DNA damage during decidualization through the ATR/ATM-CHK1-E2F1 pathway. The weight of implantation sites and deciduoma was effectively reduced by specific inhibitors for RRM2. The expression of decidual/trophoblast prolactin-related protein (Dtprp), a reliable marker for decidualization in mice, was significantly reduced in deciduoma and steroid-induced decidual cells after HU treatment. Therefore, RRM2 may be an important effector of progesterone signaling to induce cell proliferation and decidualization in mouse uterus.
Background: Ribonucleotide reductase M2 (RRM2) is a rate-limiting step for DNA synthesis. It is still unknown how RRM2 is involved in decidualization.
Results: RRM2 is highly expressed in the decidua and up-regulated by progesterone and DNA damage. Decidualization is significantly inhibited by specific RRM2 inhibitors.
Conclusion: RRM2 is essential for mouse decidualization.
Significance: This study will shed light on understanding the mechanism underlying decidualization.
The performance of electrochemical actuators is mainly based on the migration path of the electron/ion, the ion storage space, and the mechanical strength. Despite many studies devoted to developing ...elaborate hierarchical architectures of electrode materials to achieve a better actuation effect, the underlying relationship between the dimensions of materials and the actuation properties has been seldom investigated. Herein, three different dimensions of Ni-1,4-benzenedicarboxylic acid microstructures sharing the same composition and crystal phase were introduced into the PEDOT:PSS electrode layer. By comparing their conductivity, capacitance, and the mechanical properties, the two-dimensional Ni-1,4-benzenedicarboxylic acid sample exhibited the best electrical conductivity (175.1 S cm–1), ion conductivity (1.07 × 10–4 S cm–1), charge transfer resistance (3.48 Ω), capacitance (12.64 mF cm–2), response speed (1.02 mm s–1), Young’s modulus (34.89 MPa), and stress (0.195 mN). Under low-voltage testing conditions of ±3 V, the deflection displacement reached 17.6 mm, which is four times higher than that of the pure PEDOT:PSS electrode (4.2 mm). The driving strain was as high as 0.57% (PEDOT:PSS’s driving strain was 0.2%), and the electromechanical conversion efficiency was 2.78%, attributed to two-dimensional nanostructures providing a large surface area and abundant active sites for electrochemical reaction. The unique two-dimensional layer promotes a faster diffusion and accumulation of ions on the entire electrode and shortens the diffusion distance of ions in the electrochemical reaction process.
Background
Clinical characteristics of patients with the coronavirus disease 2019 (COVID-19) may present differently within and outside the epicenter of Wuhan, China. More clinical investigations are ...needed.
Objective
The study was aimed to describe the clinical characteristics, laboratory parameters, and therapeutic methods of COVID-19 patients in Hunan, China.
Setting
The First Hospital of Changsha, First People’s Hospital of Huaihua, and the Central Hospital of Loudi, Hunan province, China.
Methods
This was a retrospective multi-center case-series analysis. Patients with confirmed COVID-19 diagnosis hospitalized at the study centers from January 17 to February 10, 2020, were included. The following data were obtained from electronic medical records: demographics, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, computer tomography scans, and treatment measures.
Main outcome measure
Epidemiological, clinical, laboratory, and radiological characteristics and treatments.
Results
A total of 54 patients were included (51 had the common-type COVID-19, three had the severe-type), the median age was 41, and 52% of them were men. The median time from the first symptoms to hospital admission was seven days. Among patients with the common-type COVID-19, the median length of stay was nine days, and 21 days among patients with severe COVID-19. The most common symptoms at the onset of illness were fever (74.5%), cough (56.9%), and fatigue (43.1%) among patients in the common-type group. Fourteen patients (37.8%) had a reduced WBC count, 23 (62.2%) had reduced eosinophil ratio, and 21 (56.76%) had decreased eosinophil count. The most common patterns on chest-computed tomography were ground-glass opacity (52.2%) and patchy bilateral shadowing (73.9%). Pharmacotherapy included recombinant human interferon α2b, lopinavir/ritonavir, novaferon, antibiotics, systematic corticosteroids and traditional Chinese medicine prescription. The outcome of treatment indicated that in patients with the common-type COVID-19, interferon-α2b, but not novaferon, had some benefits, antibiotics treatment was not needed, and corticosteroids should be used cautiously.
Conclusion
As of February 10, 2020, the symptoms of COVID-19 patients in Hunan province were relatively mild comparing to patients in Wuhan, the epicenter. We observed some treatment benefits with interferon-α2b and corticosteroid therapies but not with novaferon and antibiotic treatment in our study population.
The electronic structures and magnetic properties of Ag‐doped SnO2 have been investigated using first‐principles spin‐polarized calculations based on density functional theory. Our results ...demonstrate that Ag doping introduces spin polarization in SnO2 and gives rise to a local magnetic moment of 1.0 µB per substitutional silver ion. The hole‐mediated ferromagnetic (FM) coupling between two Ag ions in this material is possibly ascribed to a p–d hopping interaction between O and Ag ions. The oxygen vacancy (VO) plays an important role in determining the magnetic properties of the Ag‐doped SnO2 system. It is found that the VO does not induce magnetism in bulk SnO2. The VO enhances stability of the spin‐polarized state for the case of the single‐Ag‐doped system, and imposes an intricate effect on a pair of Ag‐doped configurations. For example, the FM coupling between two Ag ions is possibly reinforced if VO is sufficiently far away from them. The result indicates that Ag‐doped SnO2 is a promising candidate for applications in future spintronic devices.
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