Background and aims
Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI ...classification schemes based on standardized gross sampling protocols of HCC are available at present.
Methods
119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG.
Results
The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%,
p
= 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%,
p
= 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (
p
< 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (
p
< 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS.
Conclusions
SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Alteration in reproductive hormones profile is associated with the increasing risk of menopausal depression in women. Serum follicle-stimulating hormone (FSH) level is changed during the menopause ...transition, while the effect of FSH on menopausal depression has remained undefined. In this study we investigated whether or how FSH affected menopausal depression in postmenopausal (ovariectomized) FSHR knockout mice (Fshr
). We found that Fshr
mice displayed aggravated depression-like behaviors, accompanied by severe oxidative stress in the whole brain, resulted from significantly reduced glutamate cysteine ligase modifier subunit (GCLm) in glutathione synthesis and glucose-6-phosphate dehydrogenase (G6PD) in NADP/NADPH transition. Importantly, administration of ROS scavenger N-acetyl cysteine (NAC, 150 mg · kg
· d
, i.p. for 12 weeks) attenuated the depression-like behaviors of Fshr
mice. Consistent with these in vivo experiment results, we found that pretreatment with FSH (50, 100 ng/mL) dose-dependently increased protein levels of GCLm and G6PD, and decreased the ROS production in N2a mouse neuroblastoma cells. These findings demonstrate that FSH signaling is involved in pathogenesis of menopausal depression, and likely to maintain the redox-optimized ROS balance in neurons.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized.
Hospitalized patients with COVID-19 in Zhejiang ...Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared.
Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median interquartile range {IQR} age, 47.0 35.0-55.0 years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups.
We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.
In this study, researchers describe the clinical characteristics of coronavirus disease 2019 in a selected cohort of 1099 patients with laboratory-confirmed disease throughout mainland China during ...the first 2 months of the current outbreak.
Ethylene gas is essential for many developmental processes and stress responses in plants. ETHYLENE INSENSITIVE2 (EIN2), an NRAMP-like integral membrane protein, plays an essential role in ethylene ...signaling, but its function remains enigmatic. Here we report that phosphorylation-regulated proteolytic processing of EIN2 triggers its endoplasmic reticulum (ER)–to–nucleus translocation. ER-tethered EIN2 shows CONSTITUTIVE TRIPLE RESP0NSE1 (CTR1) kinase-dependent phosphorylation. Ethylene triggers dephosphorylation at several sites and proteolytic cleavage at one of these sites, resulting in nuclear translocation of a carboxyl-terminal EIN2 fragment (EIN2-C'). Mutations that mimic EIN2 dephosphorylation, or inactivate CTR1, show constitutive cleavage and nuclear localization of EIN2-C' and EIN3 and EIN3-LIKE1-dependent activation of ethylene responses. These findings uncover a mechanism of subcellular communication whereby ethylene stimulates phosphorylation-dependent cleavage and nuclear movement of the EIN2-C' peptide, linking hormone perception and signaling components in the ER with nuclear-localized transcriptional regulators.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract
Backgroud
The current diagnostic criteria for refractory
Mycoplasma pneumoniae
pneumonia (RMPP) among
Mycoplasma pneumoniae
Pneumonia (MPP) are insufficient for early identification, and ...potentially delayed appropriate treatment. This study aimed to develop an effective individualized diagnostic prediction nomogram for pediatric RMPP.
Methods
A total of 517 hospitalized children with MPP, including 131 with RMPP and 386 without RMPP (non-RMPP), treated at Lianyungang Maternal and Child Health Care Hospital from January 2018 to December 2021 were retrospectively enrolled as a development (modeling) cohort to construct an RMPP prediction nomogram. Additionally, 322 pediatric patients with MPP (64 with RMPP and 258 with non-RMPP, who were treated at the Affiliated Hospital of Xuzhou Medical University from June 2020 to May 2022 were retrospectively enrolled as a validation cohort to assess the prediction accuracy of model. Univariable and multivariable logistic regression analyses were used to identify RMPP risk factors among patients with MPP. Nomogram were generated based on these risk factors using the rms package of R, and the predictive performance was evaluated based on receiver operating characteristic (ROC) curves and using decision curve analysis (DCA).
Results
Multivariate analysis revealed five significant independent predictors of RMPP among patients with MPP: age (hazard ratio
HR
1.16, 95% confidence interval
CI
1.08–1.33,
P
= 0.038), fever duration (
HR
1.34, 95%
CI
1.20–1.50,
P
< 0.001), lymphocyte count (
HR
0.45, 95%
CI
0.23–0.89,
P
= 0.021), serum D-dimer (D-d) level (
HR
1.70, 95%
CI
1.16–2.49,
P
= 0.006), and pulmonary imaging score (
HR
5.16, 95%
CI
2.38–11.21,
P
< 0.001). The area under the ROC curve was 90.7% for the development cohort and 96.36% for the validation cohort. The internal and external verification calibration curves were almost linear with slopes of 1, and the DCA curve revealed a net benefit with the final predictive nomogram.
Conclusion
This study proposes a predictive nomogram only based on five variables. The nomogram can be used for early identification of RMPP among pediatric patients with MPP, thereby facilitating more timely and effective intervention.
Background
Preoperative evaluation of the consistency of pituitary macroadenomas is important for neurosurgeons to prepare the surgical plan.
Purpose
To evaluate the diagnostic performance of texture ...analysis (TA) of diffusion‐weighted imaging (DWI) at a standard b‐value (b = 1000 s/mm2) and a high b‐value (b = 2000 s/mm2) for their ability to assess the tumor consistency of pituitary macroadenomas.
Study Type
Retrospective.
Population/Subjects
Fifty patients with histologically confirmed pituitary macroadenomas were classified as soft (n = 37) or hard (n = 13) types.
Field Strength/Sequence
Coronal T2‐weighted imaging (T2WI), Readout Segmentation of Long Variable Echo‐trains (RESOLVE) DWI at b = 1000 s/mm2 and b = 2000 s/mm2 were acquired with 3.0T MRI.
Assessment
The corresponding apparent diffusion coefficient (ADC) maps (ADC1000 and ADC2000) were registered to T2WI. Regions of interest (ROIs) were manually drawn along the solid part of the tumor from the coregistered T2WI‐ADC images. The texture parameters from T2WI, ADC1000, and ADC2000 were acquired.
Statistical Tests
The texture parameters were compared between the two types by using unpaired Student's t‐test. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to assess their diagnostic performance.
Results
Significant differences in TA parameters of ADC1000 and ADC2000 were observed between soft and hard types (P < 0.05 for all), whereas the TA of T2WI resulted in no significant difference (P > 0.05 for all). TA of ADC2000 provided a superior diagnostic performance compared with that of ADC1000 (P = 0.038). A combination of mean value and entropy of ADC2000 yielded an AUC, a sensitivity, and a specificity of 0.911, 78.4% and 92.3%, respectively.
Data Conclusion
TA of ADC values were useful for assessing the tumor consistency of pituitary macroadenomas. ADC2000 may facilitate better type discrimination.
Level of Evidence: 3
Technical Efficacy Stage: 2
J. Magn. Reson. Imaging 2020;51:1507–1513.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Forty compounds were isolated and characterized from A. tenuissimum flower. Among them, twelve flavonoids showed higher α−glucosidase inhibition activities in vitro than acarbose, especially ...kaempferol. The molecular docking results showed that the binding of kaempferol to α−glucosidase (GAA) could reduce the hydrolysis of substrates by GAA and reduce the glucose produced by hydrolysis, thus exhibiting α−glucosidase inhibition activities. The in vivo experiment results showed that flavonoids−rich A. tenuissimum flower could decrease blood glucose and reduce lipid accumulation. The protein expression levels of RAC−alpha serine/threonine−protein kinase (AKT1), peroxisome proliferator activated receptor gamma (PPARG), and prostaglandin G/H synthase 2 (PTGS2) in liver tissue were increased. In addition, the Firmicutes/Bacteroidetes (F/B) ratio was increased, the level of gut probiotics Bifidobacterium was increased, and the levels of Enterobacteriaceae and Staphylococcus were decreased. The carbohydrate metabolism, lipid metabolism, and other pathways related to type 2 diabetes mellitus were activated. This study indicating flavonoids−rich A. tenuissimum flower could improve glycolipid metabolic disorders and inflammation in diabetic mice by modulating the protein expression and gut microbiota.
During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in ...other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences.
Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined.
At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7
44.9 years), had more cases with comorbidity (32.9%
19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7
4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0%
11.1%, death rate 7.3%
0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4
4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)).
There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.
The cistrome is the complete set of transcription factor (TF) binding sites (cis-elements) in an organism, while an epicistrome incorporates tissue-specific DNA chemical modifications and TF-specific ...chemical sensitivities into these binding profiles. Robust methods to construct comprehensive cistrome and epicistrome maps are critical for elucidating complex transcriptional networks that underlie growth, behavior, and disease. Here, we describe DNA affinity purification sequencing (DAP-seq), a high-throughput TF binding site discovery method that interrogates genomic DNA with in-vitro-expressed TFs. Using DAP-seq, we defined the Arabidopsis cistrome by resolving motifs and peaks for 529 TFs. Because genomic DNA used in DAP-seq retains 5-methylcytosines, we determined that >75% (248/327) of Arabidopsis TFs surveyed were methylation sensitive, a property that strongly impacts the epicistrome landscape. DAP-seq datasets also yielded insight into the biology and binding site architecture of numerous TFs, demonstrating the value of DAP-seq for cost-effective cistromic and epicistromic annotation in any organism.
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•2.7 million binding targets for hundreds of TFs define the Arabidopsis cistrome•Methylation sensitivities of 76% of TFs surveyed shape the Arabidopsis epicistrome•Strong enrichment of relevant gene functions is predicted for TF target genes•Auxin response factor motif architecture promotes cooperative binding
A new method for pinpointing transcription factor binding sites in the Arabidopsis genome and their responsiveness to DNA methylation demonstrates the impact of tissue-specific DNA chemical modifications on gene regulation, potentially for any organism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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