Noninvasive identification of SOX9 status using radiomics signatures may help construct personalized treatment strategy in hepatocellular carcinoma.

OBJECTIVES: To develop and validate a radiomics-based model for predicting SOX9-positive hepatocellular carcinoma (HCC) using preoperative contrast-enhanced computed tomography (CT) images. METHODS: From January 2013 to April 2017, patients with histologically proven HCC who received systemic sorafenib treatment after curative resection were retrospectively enrolled. Radiomic features were extracted from portal venous phase CT images and selected to build a radiomics score using logistic regression analysis. The factors associated with SOX9 expression were selected and combined by univariate and multivariate analyses to establish clinico-liver imaging (CL) model and clinico-liver imaging-radiomics (CLR) model. Diagnostic performance was measured by area under curve (AUC). Overall survival (OS) and recurrence-free survival (RFS) rates were compared using Kaplan-Meier method. RESULTS: A total of 108 patients (training cohort: n = 80; validation cohort: n = 28) were enrolled. Multivariate analyses revealed that the albumin-bilirubin grade and tumor size were significant independent factors for predicting SOX9-positive HCCs and were included in the CL model. The CLR model integrating the radiomics score with albumin-bilirubin grade and tumor size showed better discriminative performance than the CL model with AUCs of 0.912 and 0.790 in the training and validation cohorts. Survival curves for RFS and OS showed that SOX9 expression was closely related to the prognosis of HCC patients. RFS and OS rates were significantly lower in patients with SOX9-positive than SOX9-negative (51.02% vs. 75.00% at 1-year RFS rates; 76.92% vs. 94.94% at 2-year OS rates). CONCLUSION: Radiomics signatures may serve as noninvasive predictors for SOX9 status evaluation in patients with HCC and may aid in constructing individualized treatment strategies.

Radiomics signature: A potential biomarker for ß-arrestin1 phosphorylation prediction in hepatocellular carcinoma.

BACKGROUND: The phosphorylation status of ß-arrestin1 influences its function as a signal strongly related to sorafenib resistance. This retrospective study aimed to develop and validate radiomics-based models for predicting ß-arrestin1 phosphorylation in hepatocellular carcinoma (HCC) using whole-lesion radiomics and visual imaging features on preoperative contrast-enhanced computed tomography (CT) images. AIM: To develop and validate radiomics-based models for predicting ß-arrestin1 phosphorylation in HCC using radiomics with contrast-enhanced CT. METHODS: Ninety-nine HCC patients (training cohort: n = 69; validation cohort: n = 30) receiving systemic sorafenib treatment after surgery were enrolled in this retrospective study. Three-dimensional whole-lesion regions of interest were manually delineated along the tumor margins on portal venous CT images. Radiomics features were generated and selected to build a radiomics score using logistic regression analysis. Imaging features were evaluated by two radiologists independently. All these features were combined to establish clinico-radiological (CR) and clinico-radiological-radiomics (CRR) models by using multivariable logistic regression analysis. The diagnostic performance and clinical usefulness of the models were measured by receiver operating characteristic and decision curves, and the area under the curve (AUC) was determined. Their association with prognosis was evaluated using the Kaplan-Meier method. RESULTS: Four radiomics features were selected to construct the radiomics score. In the multivariate analysis, alanine aminotransferase level, tumor size and tumor margin on portal venous phase images were found to be significant independent factors for predicting ß-arrestin1 phosphorylation-positive HCC and were included in the CR model. The CRR model integrating the radiomics score with clinico-radiological risk factors showed better discriminative performance (AUC = 0.898, 95%CI, 0.820 to 0.977) than the CR model (AUC = 0.794, 95%CI, 0.686 to 0.901; P = 0.011), with increased clinical usefulness confirmed in both the training and validation cohorts using decision curve analysis. The risk of ß-arrestin1 phosphorylation predicted by the CRR model was significantly associated with overall survival in the training and validation cohorts (log-rank test, P < 0.05). CONCLUSION: The radiomics signature is a reliable tool for evaluating ß-arrestin1 phosphorylation which has prognostic significance for HCC patients, providing the potential to better identify patients who would benefit from sorafenib treatment.

The Chinese herb Fructus Broussonetiae aids learning and memory in chronic cerebral hypoperfusion by reducing proinflammatory microglia activation in rats.

The neuroprotective role of Fructus Broussonetiae in a model of chronic cerebral hypoperfusion with cognitive decline was focused on neural plasticity and microglia/macrophage polarization. Chronic cerebral hypoperfusion was induced by bilateral common carotid artery ligation. Fructus Broussonetiae shortened escape latency and added the number of platform crossings of rats, up-regulated the expression of synaptophysin in the gray matter and increased myelin basic protein expression in the white matter. Further mechanistic experiments were conducted to examine microglia activation and M1/M2 polarization. It was shown that Fructus Broussonetiae reduced the activation of microglia revealed by decreased expression of ionized calcium-binding adapter molecule-1, inhibited M1 polarization of microglia and improved microglial M2 polarization shown by down-regulated the expression of inducible nitric oxide synthase and Fc fragment of IgG receptor IIIa and up-regulated the expression of arginase-1. In conclusion, the Chinese herb Fructus Broussonetiae can improve cognitive function following chronic cerebral hypoperfusion by down-regulating the activation of microglia, inhibiting microglial M1 polarization, and improving neural plasticity.

Huoluo Yinao decoction mitigates cognitive impairments after chronic cerebral hypoperfusion in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoluo Yinao decoction (HLYND) has been used to ameliorate cognitive impairment induced by chronic cerebral hypoperfusion in clinical for years. However, the exact mechanisms remain unknown. AIM OF THE STUDY: To investigate the effects and mechanisms underlying HLYND-mediated improvement in cognitive deficits associated with chronic cerebral hypoperfusion. MATERIALS AND METHODS: Thirty-six Sprague-Dawley rats were randomly allocated to three groups: sham, model, and HLYND. Daily administration of HLYND or volume-matched vehicle by gavage was initiated 1 day after bilateral carotid artery stenosis (BCAS) and continued for 42 days. The Morris water maze (MWM) test was used to assess cognitive functions from days 36-42. Via western blot and immunofluorescent staining, restoration of neuronal plasticity and remyelination of white matter were evaluated by analyzing the expression profiles of MAP-2, synaptophysin and MBP. In addition, macrophage/microglial activation was assessed by quantifying changes in Iba1, and macrophage/microglial polarization was assessed by changes in iNOS and CD16 (M1 markers), as well as Arg1 and CD206 (M2 markers). RESULTS: In the MWM test, BCAS rats showed significantly extended escape latency and reduced platform crossing times, while those in the HLYND group had shortened escape latency and increased frequency of platform crossing. In addition, rats in the model group showed decreased levels and abnormal morphological changes of MAP-2, synaptophysin and MBP, whereas HLYND administration reversed these effects. As expected, Iba1 levels were elevated in both the model and HLYND groups but rats in the model group showed increased levels of the M1 markers, iNOS and CD16, and a correspondent decrease in the M2 marker, Arg1. In contrast, in the HLYND group, iNOS and CD16 levels were suppressed, while Arg1 levels were elevated. CONCLUSIONS: Our findings demonstrate that HLYND mitigates cognitive impairment after chronic cerebral hypoperfusion in rats through mechanisms involving increased neuronal plasticity and white matter remyelination, with a subtile modulation of macrophage/microglial polarization toward the M2 phenotype.

Apatinib for treating advanced intrahepatic cholangiocarcinoma after failed chemotherapy: A case report and literature review.

RATIONALE: Intrahepatic cholangiocarcinoma (ICC) originates from the secondary branch of the bile duct and the intrahepatic bile duct epithelial cells, and is a rare pathological type of primary liver cancer. Recently, apatinib has been successfully used for a variety of malignancies. PATIENT CONCERNS: A 23-year-old female was noted with intermittent right upper abdominal distension, abdominal pain, and vomiting after eating for more than 1 month. The enhanced CT scan revealed multiple intrahepatic lesions, portal vein and right branch tumor emboli were present. DIAGNOSIS: Combined with the patient's medical history and pathology and immunohistochemistry, the diagnosis was confirmed as locally advanced unresectable ICC (cT4N1M1, Stage IVB). INTERVENTIONS: The disease progressed after six cycles of gemcitabine plus capecitabine chemotherapy. She received oral apatinib treatment since September 30, 2017. Due to related adverse reactions, the patient could not tolerate the treatment, and the subsequent reduction therapy was given. OUTCOMES: On April 11, 2018, the review of CT evaluation suggested that the disease was progressed. Hence, in this patient, apatinib as second-line treatment for advanced ICC showed a progression-free survival with 6 months. LESSONS: Apatinib as second-line treatment for advanced ICC is effective, and the adverse effects are tolerable. However, the efficacy and safety of apatinib in the treatment of ICC need to be further confirmed by large sample of prospective randomized controlled trials.

High-throughput sequencing of microbial community diversity in soil, grapes, leaves, grape juice and wine of grapevine from China.

In this study Illumina MiSeq was performed to investigate microbial diversity in soil, leaves, grape, grape juice and wine. A total of 1,043,102 fungal Internal Transcribed Spacer (ITS) reads and 2,422,188 high quality bacterial 16S rDNA sequences were used for taxonomic classification, revealed five fungal and eight bacterial phyla. At the genus level, the dominant fungi were Ascomycota, Sordariales, Tetracladium and Geomyces in soil, Aureobasidium and Pleosporaceae in grapes leaves, Aureobasidium in grape and grape juice. The dominant bacteria were Kaistobacter, Arthrobacter, Skermanella and Sphingomonas in soil, Pseudomonas, Acinetobacter and Kaistobacter in grape and grapes leaves, and Oenococcus in grape juice and wine. Principal coordinate analysis showed structural separation between the composition of fungi and bacteria in all samples. This is the first study to understand microbiome population in soil, grape, grapes leaves, grape juice and wine in Xinjiang through High-throughput Sequencing and identify microorganisms like Saccharomyces cerevisiae and Oenococcus spp. that may contribute to the quality and flavor of wine.

Luoyutong Treatment Promotes Functional Recovery and Neuronal Plasticity after Cerebral Ischemia-Reperfusion Injury in Rats.

Luoyutong (LYT) capsule has been used to treat cerebrovascular diseases clinically in China and is now patented and approved by the State Food and Drug Administration. In this retrospective validation study we investigated the ability of LYT to protect against cerebral ischemia-reperfusion injury in rats. Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion followed by reperfusion. Capsule containing LYT (high dose and medium dose) as treatment group and Citicoline Sodium as positive control treatment group were administered daily to rats 30 min after reperfusion. Treatment was continued for either 3 days or 14 days. A saline solution was administered to control animals. Behavior tests were performed after 3 and 14 days of treatment. Our findings revealed that LYT treatment improved the neurological outcome, decreased cerebral infarction volume, and reduced apoptosis. Additionally, LYT improved neural plasticity, as the expression of synaptophysin, microtubule associated protein, and myelin basic protein was upregulated by LYT treatment, while neurofilament 200 expression was reduced. Moreover, levels of brain derived neurotrophic factor and basic fibroblast growth factor were increased. Our results suggest that LYT treatment may protect against ischemic injury and improve neural plasticity.

[Relationship between the level of waist circumference and the impaired fasting glucose of pre-diabetes].

OBJECTIVE: To explore the relationship between the level of waist circumference (WC) and the impaired fasting glucose (IFG) in people working for the Kailuan Enterprise. METHODS: A total of 101 510 subjects from the employees of Kailuan Group who took part in the health examination between 2006 to 2007, with fasting plasma glucose (FPG) < 6.1 mmol/L, no history of diabetes, completed data on FPG and WC examination and without using hypoglycemic agents, were selected as the observation cohort. Subjects who did not participate in the health examination from 2010 to 2011 and had incomplete data were finally excluded, ended up with 52 099 subjects available for final analysis. According to the baseline WC measurements and its quartile in the health examinations during 2006 to 2007, people under observation were divided into four groups (first, second, third and the forth quartile groups). Multiple logistic regression analysis was used to test the relation between the increasing of WC and IFG. RESULTS: (1) The incidence rate of IFG in the obese group was higher than that in non-obese group (10.5% vs. 6.8% , P < 0.01), along with an increasing WC noticed in the 4 quartile groups and the incidence rates of IFG were progressively increased, being 6.0%, 7.1%, 8.6% and 11.0% respectively in the total population(7.0%, 7.9%, 9.1% and 11.4% in males, 2.5%, 4.6%, 6.8% and 9.8% in females). (2)Results from the multiple logistic regression analysis showed that, when compared with the first quartile group, the second, third and fourth quartile groups had increased risks of IFG after adjustment on age, gender and other risk factors in the total population, with the OR values being 1.03, 1.15 and 1.30 respectively. After adjusting the above factors in genders, we also noticed the increased risks of IFG, with the OR value being 1.45, 1.66 and 2.08 in males, while 1.00, 1.09 and 1.23 in females, respectively. The influence of the second and third quartile groups on IFG was not significant in females, however. CONCLUSION: The incidence of IFG showed an increasing trend with the increase of WC.

[Impact of baseline pulse pressure on new-onset cardio-and cerebrovascular events in diabetic population].

OBJECTIVE: To observe the association between baseline pulse pressure (PP) level and new-onset cardio-cerebrovascular events in diabetic population. METHODS: Physical examination data between July 2006 to October 2007 from a total of 101 510 employees of Kailuan Group were reviewed, 8306 subjects with a fasting plasma glucose level of ≥ 7.0 mmol/L or with confirmed diabetes diagnosis and were enrolled in this prospective cohort study. Subjects were followed up for 38-53 (48.1 ± 3.1) months and the cardio-cerebrovascular events were obtained every six months, association between baseline PP and new-onset cardio-cerebrovascular events in the diabetic population were analyzed. RESULTS: (1) Incidences of total cardio-cerebrovascular events in the PP groups were 3.4%, 2.8%, 4.5%, 6.4%, respectively. Incidences of cerebral infarction events and myocardial infarction were 2.1%, 1.6%, 2.9%, 3.9% and 1.1%, 0.7%, 1.0%, 1.7%, respectively. (2) Multivariate Cox's proportional hazards regression analysis indicated that baseline PP group was the risk factor for total cardio-cerebrovascular events, cerebral infarction events and myocardial infarction, and the risk for all the events of the PP ≥ 60 mm Hg (1 mm Hg = 0.133 kPa) group was increasing. The values of RR(95%CI) were 1.88 (95%CI 1.34-2.65, P < 0.01), 1.92 (95%CI 1.23-2.99, P < 0.01) and 1.52 (95%CI 0.82-2.81, P > 0.05) after adjust the other factors.(3) In line with increasing level of baseline PP, age, BMI, SBP, DBP, HDL-C, and hs-CRP levels significantly increased in this diabetic population (P < 0.01 or P < 0.05). CONCLUSION: The level of high baseline PP is a risk factor for new-onset cardio-cerebrovascular events in diabetic population.

[Association between baseline high sensitivity C-reactive protein level and the first cardio-cerebral vascular event in diabetic population: a prospective cohort study].

OBJECTIVE: To evaluate the predictive value of baseline serum high sensitivity C-reactive protein for the first cardio-cerebral vascular event in the population with diabetes. METHOD: In this prospective cohort study, a total of 101 510 employees of Kai Luan Group, who received healthy examination from July 2006 to October 2007, were screened and 7865 subjects with fasting plasma glucose ≥ 7.0 mmol/L or known diabetes mellitus and under insulin or hypoglycemic drugs therapy were followed up for 38 - 53 (48.02 ± 3.14) months. RESULTS: (1) Incidence rates of total cardio-cerebral vascular events, cerebral infarction and myocardial infarction increased in proportion to increased levels of baseline hsCRP (P < 0.01). After adjusting for age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and cigarette smoking, multivariate Cox's proportional hazards regression analysis indicated that the individuals in the highest quartile of hsCRP levels group (hsCRP ≥ 2.50 mg/L) had an increased risk of total cardio-cerebral vascular events (RR: 1.64, 95% CI: 1.20 - 2.24), cerebral infarction (RR: 1.52, 95% CI: 1.03 - 2.24), myocardial infarction (RR: 2.57, 95% CI: 1.34 - 4.91) compared with those in the lowest quartile group (hsCRP < 0.41 mg/L). (2) Higher baseline hsCRP levels were associated with aging, female gender, higher BMI, SBP, DBP, fasting blood glucose, TC, TG, LDL-C levels and lower HDL-C levels (all P < 0.05). CONCLUSION: Baseline hsCRP level is associated with increased first cardio-cerebral vascular event in the population with diabetes.

[The distribution and influential factors of serum high sensitivity C-reactive protein in general population].

OBJECTIVE: To observe the distribution and influence factors of serum high sensitivity C-reactive protein (hs-CRP) in general population. METHODS: In a cross-sectional population survey, a total of 101 510 subjects who were employed by Kailuan Group had been carried out a healthy examination in the period of 2006 to 2007. In the statistical analysis, we observed 91 123 subjects (males 72 805, females 18 318) who had full information and met the inclusion criteria of the study. RESULTS: (1) The geometric means of hs-CRP were 0.70 mg/L, 0.70 mg/L and 0.73 mg/L in all subjects, males and females, respectively, the 95th percentiles were 6.28 mg/L, 6.20 mg/L and 6.49 mg/L, respectively. The concentrations of hs-CRP increased with age in both males and females (P trend = 0.001). Serum hs-CRP geometric mean was 0.54 mg/L and the 95th percentile was 5.40 mg/L in health group, while the geometric mean was 0.80 mg/L and the 95th percentile was 6.57 mg/L in non-health group. (2) Multiple linear regression analysis showed that concentrations of hs-CRP were positively associated with gender, age, systolic blood pressure, body mass index, total cholesterol, triglycerides, fasting blood glucose, smoking history, history of coronary heart disease and stroke history, but concentrations of hs-CRP were inversely related with diastolic blood pressure, high-density lipoprotein cholesterol and alcohol history. CONCLUSION: Serum concentrations of hs-CRP level increased with age, concentrations of hs-CRP were higher in females than males; a variety of cardiovascular factors effected the concentrations of hs-CRP.

2-(2-Chloro-pyrimidin-4-yl)-3,5,6,7,8,9-hexahydro-2H-1,2,4-triazolo[4,3-a]azepin-3-one.

In the title compound, C(11)H(12)ClN(5)O, the triazolone and pyrimidine rings are almost coplanar [dihedral angle = 2.98 (14)°]. The total puckering amplitude Q(T) of the seven-membered lactam ring is 0.706 (3) Å.

1-Allyl-3-amino-1H-pyrazole-4-carboxylic acid.

The title compound, C(7)H(9)N(3)O(2), was prepared by alkaline hydrolysis of ethyl 1-allyl-3-amino-1H-pyrazole-4-carboxyl-ate. The crystal structure is stabilized by three types of inter-molecular hydrogen bond (N-H⋯O, N-H⋯N and O-H⋯N).

[Non-saponins from Solanum nigrum L].

OBJECTIVE: Chemical constituents of the non-saponins from Solonum nigrum L. were studied. METHODS: The separation was performed on the silic gel CC, Sephadex-LH20 CC as well as preparative HPLC. The constituents were isolated and identified by spectral methods. RESULTS: Five compounds isolated from 60% ethanol extract werre identified as 6-methoy-hydroxycoumarin (I), syringaresinol-4-O-beta-D-glucopyranoside (II), pinoresinol-4-O-beta-D-glucopyranoside (III), 3, 4-dihydroxhbenzoic acid (IV), p-hydroxybenzoic acid (V), 3-methoxy-4-hydroxyienzoic acid (VI), adenosine (VII). CONCLUSION: II, III, and VII were isolated from this genus for the first time.

[Comparison between tow methods of acute physiology and chronic health evaluation III and acute lung injury scale to evaluate the severity and prognosis of severe acute respiratory syndrome].

OBJECTIVE: To evaluate the acute physiology and chronic health evaluation III (APACHE III) and acute lung injury (ALI) scale in the severity and prognosis of severe acute respiratory syndrome (SARS). METHODS: The clinical data of 38 SARS patients, including survivors (24 cases) and no survivors (14 cases) were collected and evaluated with APACHE III and ALI scoring systems. The correlation of scores and prognosis was evaluated. RESULTS: The scores of APACHE III in the non survivors were higher remarkably than those in the survivor group (P < 0.001). The scores of APACHE III had positive correlation with the overall fatality rate. When the scores of APACHE III was higher than 60, the mortality increased obviously (chi(2) = 3.886, P < 0.05). Elderly patients with SARS who were over 60 years old had a high mortality (chi(2) = 8.660, P < 0.05). The scores of ALI in the non survivors had not statistical significance than those in the survivor group (P = 0.127). CONCLUSIONS: The score of APACHE III in the SARS are correlated with the patient's condition and prognosis. Elderly patients with SARS have a high mortality.