Diagnostic performance of MRI for assessing axillary lymph node status after neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.

OBJECTIVE: This systematic review examined the diagnostic performance of magnetic resonance imaging (MRI) for assessing axillary lymph node status (ALNS) after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies and used the QUADAS-2 tool to assess methodological quality of eligible studies. We used STATA version 12.0 to perform data pooling, heterogeneity testing, subgroup analysis, and sensitivity analysis. RESULTS: For the 21 enrolled studies, including 2875 patients, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were respectively 0.63 (95% CI: 0.53-0.72), 0.75 (95% CI: 0.68-0.81), 2.52 (95% CI: 1.98-3.19), 0.50 (95% CI: 0.39-0.63), and 5.08 (95% CI: 3.38-7.63). The AUC was 0.76 (95% CI: 0.72-0.79). I2 values of sensitivity (I2 = 94.41%) and specificity (I2 = 88.97%) were both > 50%. For the initial positive ALN patients, the pooled sensitivity and specificity were 0.64 (95% CI: 0.53-0.75) and 0.74 (95% CI: 0.64-0.82), respectively. Sensitivity analyses by focusing on studies with MRI performed post-NAC, studies using DCE-MRI, or studies with low risk of bias showed similar results to the primary analyses. CONCLUSION: MRI may have suboptimal diagnostic value in assessing ALNS after NAC for breast cancer patients. Due to the inconsistency of NAC regimens, the variability of axillary surgery, and the lack of time interval between MRI and surgery, further studies are needed to confirm our findings. CLINICAL RELEVANCE STATEMENT: Our study provided the diagnostic value of MRI in assessing axillary lymph node status after neoadjuvant chemotherapy for breast cancer patients. KEY POINTS: • MRI may have suboptimal diagnostic value in assessing axillary lymph node status after NAC for general breast cancer patients. • The initial axillary lymph node status has little impact on the diagnostic efficacy of MRI. • The substantial heterogeneity among studies highlights the need for further studies to provide more high-quality evidence in this field.

Prognostic Value of Cardiac Magnetic Resonance Imaging in Chronic Aortic Regurgitation: A Systematic Review and Meta-Analysis.

Background: Chronic aortic regurgitation (AR) is a common valvular disease characterized by an overload of left ventricular volume and pressure. Accurate assessment of the heart from all angles is crucial for effective clinical management and prognostic evaluation of AR patients. As an advanced imaging technique, cardiac magnetic resonance (CMR) has become the gold standard for assessing cardiac volume and function. Accordingly, this study aimed to evaluate the prognostic value of CMR in chronic AR. Methods: EMBASE, Cochrane Library, PubMed, and Web of Science were searched for clinical studies published between inception and July 19, 2022. Only studies that used CMR to assess patients with chronic isolated AR and provided prognostic data were included. Results: For our analysis, 11 studies, which involved 1702 subjects and follow-up periods of 0.6-9.7 years, were eligible. We identified 13 CMR-related parameters associated with AR prognosis. With aortic valve surgery as the outcome, we estimated the pooled hazard ratios (HRs) for four of these parameters: aortic regurgitation fraction (ARF), aortic regurgitation volume (ARV), left ventricle end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV). The pooled HR for ARF was found to be 4.31 (95% confidence interval [CI]: 1.12-16.59, p = 0.034), while that for ARV was 3.88 (95% CI: 0.71-21.04, p = 0.116). Additionally, the combined HRs of LVEDV and LVESV were estimated to be 2.20 (95% CI: 1.04-4.67, p = 0.039) and 3.14 (95% CI: 1.22-8.07, p = 0.018), respectively. Conclusions: The assessment of ARF, LVEDV, and LVESV via CMR has significant prognostic value in predicting the prognosis of AR patients with aortic valve surgery as an endpoint. It is recommended to consider using multi-parameter CMR in the clinical management of AR patients for timely interventions and effective prognostic evaluation.

Different Imaging Modalities for the Diagnosis of Axillary Lymph Node Metastases in Breast Cancer: A Systematic Review and Network Meta-Analysis of Diagnostic Test Accuracy.

BACKGROUND: Accurate diagnosis of axillary lymph node metastasis (ALNM) of breast cancer patients is important to guide local and systemic treatment. PURPOSE: To evaluate the diagnostic performance of different imaging modalities for ALNM in patients with breast cancer. STUDY TYPE: Systematic review and network meta-analysis (NMA). SUBJECTS: Sixty-one original articles with 8011 participants. FIELD STRENGTH: 1.5 T and 3.0 T. ASSESSMENT: We used the QUADAS-2 and QUADAS-C tools to assess the risk of bias in eligible studies. The identified articles assessed ultrasonography (US), MRI, mammography, ultrasound elastography (UE), PET, CT, PET/CT, scintimammography, and PET/MRI. STATISTICAL ANALYSIS: We used random-effects conventional meta-analyses and Bayesian network meta-analyses for data analyses. We used sensitivity and specificity, relative sensitivity and specificity, superiority index, and summary receiver operating characteristic curve (SROC) analysis to compare the diagnostic value of different imaging modalities. RESULTS: Sixty-one studies evaluated nine imaging modalities. At patient level, sensitivities of the nine imaging modalities ranged from 0.27 to 0.84 and specificities ranged from 0.84 to 0.95. Patient-based NMA showed that UE had the highest superiority index (5.95) with the highest relative sensitivity of 1.13 (95% confidence interval [CI]: 0.93-1.29) among all imaging methods when compared to US. At lymph node level, MRI had the highest superiority index (6.91) with highest relative sensitivity of 1.13 (95% CI: 1.01-1.23) and highest relative specificity of 1.11 (95% CI: 0.95-1.23) among all imaging methods when compared to US. SROCs also showed that UE and MRI had the largest area under the curve (AUC) at patient level and lymph node level of 0.92 and 0.94, respectively. DATA CONCLUSION: UE and MRI may be superior to other imaging modalities in the diagnosis of ALNM in breast cancer patients at the patient level and the lymph node level, respectively. Further studies are needed to provide high-quality evidence to validate our findings. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

The recovery of KaiA's activity depends on its N-terminal domain and KaiB in the cyanobacterial circadian clock.

Circadian rhythms are the endogenous oscillation of biological reactions and behaviors in most organisms on Earth. Circadian clocks are the pacemakers regulating circadian rhythms, and the transcription-translation dependent feedback loop (TTFL) model was supposed to be the sole model of circadian clocks. However, recent years have witnessed rapid progresses in the study of non-TTFL circadian clocks. The cyanobacterial circadian clock consists of three proteins (KaiA, KaiB, and KaiC), and is extensively studied as a non-TTFL circadian clock model. Although containing only three proteins, the molecular mechanism of the KaiABC circadian clock remains elusive. We recently noticed that KaiA has an auto-inhibition conformation during the oscillation, but how this auto-inhibition is regulated is unclear. Here, we started from the design of light modulated KaiAs to investigate this mechanism. We designed different KaiA constructs fused with the light modulable LOV2 protein, and used light-modulated KaiAs to regulate the phosphorylation and dephosphorylation of KaiC. Our data indicated that the N-terminal domain of KaiA is important for KaiA's reversible off/on switching during the unidirectional oscillation of the KaiABC system. This work provides an updated model to explain the molecular mechanism of the KaiABC circadian clock.

Polyamines Disrupt the KaiABC Oscillator by Inducing Protein Denaturation.

Polyamines are positively charged small molecules ubiquitously existing in all living organisms, and they are considered as one kind of the most ancient cellular components. The most common polyamines are spermidine, spermine, and their precursor putrescine generated from ornithine. Polyamines play critical roles in cells by stabilizing chromatin structure, regulating DNA replication, modulating gene expression, etc., and they also affect the structure and function of proteins. A few studies have investigated the impact of polyamines on protein structure and function previously, but no reports have focused on a protein-based biological module with a dedicated function. In this report, we investigated the impact of polyamines (putrescine, spermidine, and spermine) on the cyanobacterial KaiABC circadian oscillator. Using an established in vitro reconstitution system, we noticed that polyamines could disrupt the robustness of the KaiABC oscillator by inducing the denaturation of the Kai proteins (KaiA, KaiB, and KaiC). Further experiments showed that the denaturation was likely due to the induced change of the thermal stability of the clock proteins. Our study revealed an intriguing role of polyamines as a component in complex cellular environments and would be of great importance for elucidating the biological function of polyamines in future.

The reversible function switching of the circadian clock protein KaiA is encoded in its structure.

BACKGROUND: Circadian rhythms are important to the evolution of organisms and human health, and recent studies proved that post-translational circadian clocks widely exist in all phyla. The circadian clock of cyanobacteria is an important model system as the first verified circadian oscillator independent of transcriptional-/translational-level regulations. This circadian oscillator consists of three proteins, KaiA, KaiB, and KaiC, in which KaiA stimulates KaiC's phosphorylation but KaiB antagonizes KaiA. Despite of intense research on the molecular mechanism of this oscillator in the last decades, the regulation mechanism of KaiA's function remains unclear. METHODS: In this study, we combined computational tools and experimental assays to study the function switching of KaiA. We adopted different strategies to re-design KaiA protein to elucidate its function switch during the circadian oscillation. RESULTS: We showed that KaiA's function switch is determined by its structural dynamics, and KaiB antagonizes KaiA by switching it from an active state to an inactive state with the help of KaiC. CONCLUSIONS: The reversible function switching of KaiA is key to the KaiABC oscillator, and the switching could be regulated by the 3-D domain swapped homo-dimer conformation of KaiA, which provides the necessary structural flexibility. GENERAL SIGNIFICANCE: Our finding updated the current knowledge on the regulation of KaiA's function. This work would deepen our understanding of the KaiABC oscillator, and should be conceptually useful in the design of artificial biological oscillators.

The Application of Iodine Quantitative Information Obtained by Dual-Source Dual-Energy Computed Tomography on Chemoradiotherapy Effect Monitoring for Cervical Cancer: A Preliminary Study.

OBJECTIVE: The aim of the study is to investigate the potential contribution of the iodine quantitative parameters of dual-phase dual-energy computed tomography (DECT) scanning for chemoradiotherapy (CRT) response monitoring for cervical cancer. METHODS: Patients who were pathologically certified having cervical cancer and intended for concurrent radiotherapy and chemotherapy were prospectively included in our study. Contrast-enhanced DECT scanning was performed before CRT, which was repeated after 1 month of therapy, using a dual-source CT scanner onset. Changes in tumor size were assessed according to RECIST 1.0. Quantification of volume-normalized iodine uptake (mg/mL) was measured in dual phases and was standardized using the iodine uptake in the iliac artery. The decreased ratio of the standard iodine uptake was calculated and compared with the tumor size for the evaluation of the CRT effect. Data were analyzed using the statistics software SPSS version 19.0. Twenty women who performed normal pelvic contrast-enhanced CT scanning were randomly chosen as the control group for the radiation dose comparison with the dual-energy group. RESULTS: A total of 21 patients who completed therapeutic courses and performed the contrast-enhanced CT scanning were subsequently evaluated. According to RECIST 1.0, 15 cases were classified into the regression (R, including 5 completed regression cases and 10 partial regression cases) group. The remaining 6 cases were classified into the nonregression (NR, including 6 stable disease cases) group. The iodine value decreased ratio in the arterial phase (standardized iodine in arterial phase [SAI]) of the partial regression group was significantly higher than that of the stable disease group (P < 0.01), and there was no significant difference in the venous phase (P > 0.05). In a general quantitative comparison between the R group and the NR group before CRT, we controlled for the maximum diameter, age, iodine uptake in the arterial phase before CRT (pre-SAI), iodine uptake in the venous phase before CRT, and cell differentiated level, and we ultimately found no significant statistical differences except for the pre-SAI. In other words, the iodine value in the arterial phase of the R group before CRT was significantly higher than that of the NR group (P < 0.01). When the pre-SAI was 0.345, the area under the curve was 0.875 for therapeutic effect prediction. The mean effective dose was 5.63 ± 1.68 mSv for the DECT group and 5.37 ± 1.82 mSv for the control group (t = -1.137, P = 0.262), which showed no statistical difference in the radiation dose between the 2 scanning methods. CONCLUSIONS: The iodine mapping can be used to help evaluate the radiochemotherapy response effectively on the basis of tumor size change and can also be helpful in predicting the radiochemotherapy outcome for cervical cancer. The dual-phase DECT scanning did not increase the radiation dose and provided more valuable information, and thus, it was suitable for promotion in clinical application.

Comparison of PET with PET/CT in detecting peritoneal carcinomatosis: a meta-analysis.

PURPOSE: The study aims to perform a meta-analysis to compare the diagnostic value of FDG PET with PET/CT in detecting peritoneal carcinomatosis (PC) to identify the potentially most useful diagnostic modality. METHODS: A computer-aided search was performed in the Cochrane Library, PubMed, EMBASE, Web of Science, the China Biological Medicine Database, VIP, China National Knowledge Infrastructure database, and Wanfang databases for articles concerning diagnosis of peritoneal metastases with PET or PET/CT. QUADAS was used to evaluate the included articles' quality. RESULTS: On a per-patient basis, the pooled sensitivity of PET/CT (84%) was significantly higher than that of PET (60%), and the pooled specificity of PET (98%) was markedly higher than that for PET/CT (94%). On a per-lesion basis, the pooled sensitivity and specificity of PET/CT were 87 and 95%, respectively. Only 1 PET study on a per-lesion basis, its sensitivity is 65.8 and specificity is 94.1%. CONCLUSIONS: PET and PET/CT are powerful imaging techniques for detection and characterization of PC. PET/CT can be used as a screening tool and it may be acceptable to use PET as a diagnosis tool.

Computed tomography for the diagnosis of gastroesophageal varices and risk assessment in patients with cirrhosis: a systematic review and meta-analysis.

PURPOSE: This meta-analysis aimed to evaluate the diagnostic accuracy of computed tomography (CT) for gastroesophageal varices (GEVs) and identify high-risk GEVs in patients with cirrhosis. METHODS: A comprehensive search of databases identified 28 studies reporting on CT-based diagnosis for GEVs confirmed via endoscopy. Meta-analyses were conducted to calculate the pooled sensitivity (SEN) and pooled specificity (SPE), positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC). RESULTS: Based on the number of patients (or varices), the pooled SEN, SPE, PLR, NLR, DOR, and AUC of CT-based diagnosis were estimated at 0.91 (0.92), 0.81 (0.45), 4.82 (1.67), 0.11 (0.17), 42.47 (10.26), and 0.93 (0.94), respectively, for any GEV and at 0.89 (0.89), 0.90 (0.79), 8.86 (4.28), 0.12 (0.14), 75.71 (30.19), and 0.95 (0.85), respectively, for high-risk GEVs. Subgroup analyses indicated that CT had a higher diagnostic accuracy for esophageal varices compared with gastric varices (AUC: 0.93 vs. 0.89, P < 0.05), and the 64-slice CT yielded superior SEN compared with 16-slice and <16-slice CT (AUC: 0.97 vs. 0.92 and 0.82, respectively, P < 0.05). Prospective studies demonstrated higher diagnostic accuracy than retrospective studies (AUC: 0.95 vs. 0.90, P < 0.05). Regarding variceal size, a cut-off of 3 mm and 5 mm discriminated between low- and high-risk individuals, respectively, with high diagnostic accuracy (AUC: 0.992 vs. 0.997, P > 0.05). CONCLUSION: CT demonstrates promising diagnostic accuracy for identifying GEVs and distinguishing high-risk GEVs in patients with cirrhosis. Further research validating optimal variceal size cut-offs is warranted to enhance clinical utility. CLINICAL SIGNIFICANCE: Such a high diagnostic accuracy of CT scans for predicting varices is clinically meaningful for patients with cirrhosis accompanied by portal hypertension. If high-risk varices are identified at CT scans, early intervention would be helpful to reduce the risk of variceal bleeding.

Xuebijing injection protects sepsis induced myocardial injury by mediating TLR4/NF-κB/IKKα and JAK2/STAT3 signaling pathways.

OBJECTIVE: Compelling evidence has demonstrated that Xuebijing (XBJ) exerted protective effects against SIMI. The aims of this study were to investigate whether TLR4/IKKα-mediated NF-κB and JAK2/STAT3 pathways were involved in XBJ's cardio-protection during sepsis and the mechanisms. METHODS: In this study, rats were randomly assigned to three groups: Sham group; CLP group; XBJ group. Rats were treated with XBJ or sanitary saline after CLP. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis were tested by TUNEL staining. The protein levels of Bax, Bcl-2, Bcl-xl, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3 in the myocardium were assayed by western blotting. And finally, immunofluorescence was used to assess the level of p-JAK2 and p-STAT3 in heart tissue. RESULTS: The results of echocardiography, myocardial enzyme and HE test showed that XBJ could significantly improve SIMI. The IL-1ß, IL-6 and TNF-α levels in the serum were markedly lower in the XBJ group than in the CLP group (p<0.05). TUNEL staining's results showed that XBJ ameliorated CLP-induced cardiomyocyte apoptosis. Meanwhile, XBJ downregulated the protein levels of Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3, as well as upregulated the protein levels of Bcl-2, Bcl-xl (p <0.05). CONCLUSIONS: In here, we observed that XBJ's cardioprotective advantages may be attributable to its ability to suppress inflammation and apoptosis via inhibiting the TLR4/ IKKα-mediated NF-κB and JAK2/STAT3 pathways during sepsis.

Chest CT findings in patients with coronavirus disease 2019 (COVID-19): a comprehensive review.

The objective of this review was to summarize the most pertinent CT imaging findings in patients with coronavirus disease 2019 (COVID-19). A literature search retrieved eligible studies in PubMed, EMBASE, Cochrane Library and Web of Science up to June 1, 2020. A comprehensive review of publications of the Chinese Medical Association about COVID-19 was also performed. A total of 84 articles with more than 5340 participants were included and reviewed. Chest CT comprised 92.61% of abnormal CT findings overall. Compared with real-time polymerase chain reaction result, CT findings has a sensitivity of 96.14% but a low specificity of 40.48% in diagnosing COVID-19. Ground glass opacity (GGO), pure (57.31%) or mixed with consolidation (41.51%) were the most common CT features with a majority of bilateral (80.32%) and peripheral (66.21%) lung involvement. The opacity might associate with other imaging features, including air bronchogram (41.07%), vascular enlargement (54.33%), bronchial wall thickening (19.12%), crazy-paving pattern (27.55%), interlobular septal thickening (42.48%), halo sign (25.48%), reverse halo sign (12.29%), bronchiectasis (32.44%), and pulmonary fibrosis (26.22%). Other accompanying signs including pleural effusion, lymphadenopathy and pericardial effusion were rare, but pleural thickening was common. The younger or early stage patients tended to have more GGOs, while extensive/multilobar involvement with consolidation was prevalent in the older or severe population. Children with COVID-19 showed significantly lower incidences of some ancillary findings than those of adults and showed a better performance on CT during follow up. Follow-up CT showed GGO lesions gradually decreased, and the consolidation lesions first increased and then remained relatively stable at 6-13 days, and then absorbed and fibrosis increased after 14 days. Chest CT imaging is an important component in the diagnosis, staging, disease progression and follow-up of patients with COVID-19.

The diagnostic performance of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in evaluating the pathological response of breast cancer to neoadjuvant chemotherapy: A meta-analysis.

PURPOSE: To evaluate and compare the diagnostic performance of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the pathological response of breast cancer to neoadjuvant chemotherapy (NAC). METHODS: We searched PubMed, EMBASE, Cochrane Library, and Web of Science systematically to identify relevant studies from inception to December 2020. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the methodological quality of the included studies. We extracted sufficient data to construct 2 × 2 tables and then used STATA 12.0 to perform data pooling, heterogeneity testing, meta-regression analysis and subgroup analysis. RESULTS: A total of 41 articles were enrolled in this study, including 27 studies (2107 patients) on DCE-MRI and 23 studies (1321 patients) on DWI. The pooled sensitivity and specificity of DCE-MRI were 0.75 and 0.79, and the pooled sensitivity and specificity of DWI were 0.77 and 0.75. There was no significant difference in sensitivity (P = 0.598) and specificity (P = 0.218) ​​between DCE-MRI and DWI. And meta-regression analysis showed that both magnetic field strength and the time of examination had significant effects on heterogeneity. CONCLUSIONS: DWI might be a potential substitute for DCE-MRI in predicting the pathological response of breast cancer to NAC as there was no significant difference in the diagnostic performance between the two. However, considering that not all included studies directly compared the diagnostic performance of DWI and DCE-MRI in the same patients and the heterogeneity of the included studies, caution should be exercised in applying our results.

The value of the signal intensity of peritumoral tissue on Gd-EOB-DTPA dynamic enhanced MRI in assessment of microvascular invasion and pathological grade of hepatocellular carcinoma.

ABSTRACT: The aim of the study was to assess the potential role of preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) dynamic enhanced MR imaging for diagnosing microvascular invasion (MVI) and pathological grade of hepatocellular carcinoma (HCC).A total of 113 consecutive HCC patients confirmed by histopathology underwent preoperative Gd-EOB-DTPA dynamic enhanced MRI were included. Signal intensity (SI) of peritumoral, normal liver tissue and tumor parenchyma during arterial phase and hepatobiliary phase (HBP) were analyzed. The receiver operating characteristic (ROC) curves were performed to assess the potential diagnostic capability for MVI and pathological grade of HCC. Kaplan-Meier method was performed to estimate the recurrence-free survival rate and compared using the log rank test.SI ratio of peritumoral tissue to normal liver in arterial phase (SIAp/Al) was independently associated with MVI [odds ratio (OR) = 3.115, 95% confidence interval (CI): 1.867-5.198] and pathological grades (OR = 1.437, 95% CI: 1.042-1.981). The area under the curve (AUC) of SIAp/Al was equivalent to the SI of tumor parenchyma on arterial phase (SIAt) in distinguishing low and high pathological grades. However, the AUC of SIAp/Al (0.851) was larger than peritumoral hypointensity on HBP (0.668) for distinguishing MVI. The recurrence-free survival rate of HCC patients with SIAp/Al<1.1 was higher than HCC with SIAp/Al≥1.1(P = .025).The SIAp/Al in preoperative Gd-EOB-DTPA dynamic enhanced MR imaging is a potential diagnosis marker for MVI and pathological grade of HCC noninvasively. The higher SIAp/Al may predict the poor prognosis of HCC after surgery.

Synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma: A case report and review of the literature.

RATIONALE: Presence of synchronous double hepatocelluar carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) (sdpHCC-ICC) located separately within a single liver is extremely rare. The purpose of this study is to investigate the clinical, imaging, pathological characteristics, and prognosis of patients with sdpHCC-ICC, in order to enhance our understanding of the disease and improve diagnostic and therapeutic effect. PATIENT CONCERNS: A 49-year-old, female with the diagnosis of hepatitis B virus with obvious liver cirrhosis, was admitted to our hospital. On admission, the levels of α-fetoprotein and carbohydrate antigen 19-9 were found to be elevated. Abdominal ultrasonography and enhanced computed tomography revealed 2 solid masses located in segments (S) 4 and 6 of the liver, with malignant behaviors. DIAGNOSES: In the light of above investigations, preoperative diagnosis of multiple primary hepatocellular carcinomas was made. INTERVENTION: Hepatic resection of both segments was done. The resected specimens revealed the presence of well-defined tumors in segments 4 and 6 measuring 5.0 cm and 2.5 cm respectively. OUTCOMES: Histopathological examination confirmed the tumor of the 4th segment to be moderately and poorly differentiated ICC, and the tumor of the 6th segment to be poorly differentiated HCC. Immunohistochemically, the ICC in S4 was positive for CK19 and negative for Heppar-1, whereas the HCC in S6 was positive for Heppar-1 and negative for CK19. Unfortunately, metastasis to multiple organs and lymph nodes were observed 3 months later. The patient died of liver failure 16 months after surgery. LESSONS: The clinical characteristics of sdpHCC-ICC are usually atypical and nonspecific making its preoperative diagnosis quite difficult. Hepatitis B virus and hepatitis C virus infection were both the independent risk factor for the development of sdpHCC-ICC. In patients with chronic liver disease, careful observation with imaging is of utmost necessity. Tumor markers may also play a valuable role in the diagnosis. The definite diagnosis depends on pathological examination. Hepatic resection is considered the most effective mode of treatment. The prognosis of synchronous occurrence of double hepatic cancers is worse than either HCC or ICC, and the origin of the disease needs further study.

[Progress in the molecular mechanism of KaiA regulating cyanobacterial circadian clock].

The cyanobacterial circadian clock has three relatively independent parts: the input path, the core oscillator, and the output path. The core oscillator is composed of three clock proteins: KaiA, KaiB, and KaiC. The interactions among these three proteins generate a rhythmic signal and convey the input signals to the output signals to maintain the accuracy and stability of the oscillation of downstream signals. Based on the cyanobacterial circadian clock and the structure, function, and interaction of the clock proteins of the core oscillator, combining the recent results from our laboratory, this review summarized the recent progresses of the molecular mechanism of KaiA in regulating KaiC's enzymatic activity, mediating phase reset of the oscillator, and competing with CikA for the binding site of KaiB.

Whole-lesion histogram analysis metrics of the apparent diffusion coefficient: a correlation study with histological grade of hepatocellular carcinoma.

PURPOSE: The study evaluated the relationship between the histological grade of hepatocellular carcinoma (HCC) and the histogram-derived parameters of apparent diffusion coefficient (ADC) obtained from the whole-lesion assessment of diffusion-weighted magnetic resonance (MR) imaging in the liver. METHODS: A total of 51 patients were included. The parameters were correlated with the Edmondson-Steiner grades by using the Spearman correlation coefficient (ρ). The differences of ADC parameters between different tumor histological grades were compared using the Mann-Whitney U test. The extent to which each parameter aided in differentiating tumors with poor performance (III, IV) and fair performance (I, II) was assessed by using the area under the receiver operating characteristic curve (Az). RESULTS: The 25th percentile ADC exhibits the most negative correlation with histological grade (ρ = - 0.397), followed by the 30th percentile ADC (ρ = - 0.395), the minimum ADC value (ρ = - 0.390) and the 20th percentile ADC (ρ = - 0.385), whereas the minimum ADC value yielded the highest Az (0.763) in the discrimination of tumor foci with poor differentiation from fairly differentiated HCCs. The minimum ADC of 4.15 × 10-3 mm2/s or lower was considered to indicate poorly differentiated performance, and the corresponding sensitivity and specificity were 66.7 and 90.9%, respectively. CONCLUSION: The 25th percentile ADC showed a stronger correlation with the histological grade of HCC than other ADC parameters, and the minimum ADC value might be an optimal metric for determining poor and fair differentiations of HCC in DWI.

The influence of KaiA mutations on its function in the KaiABC circadian clock system.

The core oscillator of the circadian clock of cyanobacteria consists of three proteins, KaiA, KaiB, and KaiC. The KaiABC oscillator can be re-constituted in vitro with the purified proteins in buffer containing ATP and Mg2+. The interaction between KaiA and KaiC has not been well studied. In this article, different KaiA mutants were designed and used to elucidate the influence of KaiA structure on its function in the in vitro system. Molecular dynamics simulations were adopted to study the structural flexibility of KaiA homodimer. The data presented in this article provide further experimental supports to our work in Chen et al. (2017) [1].

Chemical composition and synergistic antioxidant activities of essential oils from Atractylodes macrocephala and Astragalus membranaceus.

Chemical composition of the essential oils derived from Atractylodes macrocephala (AMA), Astragalus membranaceus (AME) and AMA-AME herb pair was investigated using gas chromatography-mass spectrometry (GC-MS). Antioxidant activities were evaluated by 1,1-diphenyl-2-picyrlhydrazyl (DPPH) radical-scavenging and Trolox equivalent antioxidant capacity (TEAC) assays. Forty-five, ten and forty-three components were identified in AMA, AME and AMA-AME essential oils, respectively. AMA-AME essential oil exhibited a significantly higher radical scavenging capacity than the theoretical sum of those of the respective herb essential oils (P < 0.05). Principal component analysis showed that twenty-three components contributed to the scavenging activities against DPPH and ABTS*+ radicals. Moreover, the concentrations of these major components exhibited various increases to some extent when compared with the theoretical sum of the respective herb essential oils. These findings suggest that combination of two or more herbs might be used as a promising source of natural antioxidants in the pharmaceutical and food industries.

Synergistic antioxidant activities of eight traditional Chinese herb pairs.

Many Chinese therapeutic herbs that are traditionally used in combination demonstrate significantly better pharmacological effects when used in the combination than when used alone. However, the pharmacological mechanism for this synergism is still not well understood. In the present study, the antioxidant activities of six herbs ((Paeonia lactiflora (PL), Atractylodes macrocephala (AMA), Angelica sinensis (AS), Astragalus membranaceus (AME), Glycyrrhiza uralensis (GU) and Rheum officinale (RO)), which were historically combined into eight traditional Chinese herb pairs (TCHPs) (AME-AS, AME-AMA, AME-RO, AME-GU, AME-PL, PL-AS, PL-AMA and PL-GU), were investigated in vitro by assessing the 1,1-diphenyl-2-picryl hydrazine (DPPH)-radical scavenging abilities of the herbs. The results of this study showed that all eight TCHPs had a significantly larger scavenging capacity than would be expected from the theoretical sum of those of the respective constituent herbs (p<0.05). Furthermore, the AME-GU, AME-PL and AME-AMA pairs not only showed a significant synergistic effect in the DPPH scavenging assay, but they also demonstrated similar results in hydroxyl radical and superoxide radical anion scavenging assays. Interestingly, the AME-AMA combination had a significantly higher superoxide anion (0.2 g/ml) and hydroxyl radical scavenging ability than the AME or AMA. The changes in the total phenolic and flavonoid contents were also investigated. Our study showed a significant correlation between the rate of enhancement in antioxidant capacity and the rate of increase in flavonoid content. Thus, the flavonoids are likely responsible for the synergistic effects present in TCHPs.