Photoelectrochemical Solution Gated Graphene Field-Effect Transistor Functionalized by Enzymatic Cascade Reaction for Organophosphate Detection.

Solution Gated Graphene Field-Effect Transistors (SGGT) are eagerly anticipated as an amplification platform for fabricating advanced ultra-sensitive sensors, allowing significant modulation of the drain current with minimal gate voltage. However, few studies have focused on light-matter interplay gating control for SGGT. Herein, this challenge is addressed by creating an innovative photoelectrochemical solution-gated graphene field-effect transistor (PEC-SGGT) functionalized with enzyme cascade reactions (ECR) for Organophosphorus (OPs) detection. The ECR system, consisting of acetylcholinesterase (AChE) and CuBTC nanomimetic enzymes, selectively recognizes OPs and forms o-phenylenediamine (oPD) oligomers sediment on the PEC electrode, with layer thickness related to the OPs concentration, demonstrating time-integrated amplification. Under light stimulation, the additional photovoltage generated on the PEC gate electrode is influenced by the oPD oligomers sediment layer, creating a differentiated voltage distribution along the gate path. PEC-SGGT, inherently equipped with built-in amplification circuits, sensitively captures gate voltage changes and delivers output with an impressive thousandfold current gain. The seamless integration of these three amplification modes in this advanced sensor allows a good linear range and highly sensitive detection of OPs, with a detection limit as low as 0.05 pm. This work provides a proof-of-concept for the feasibility of light-assisted functionalized gate-controlled PEC-SGGT for small molecule detection.

Meta-Analysis of the Efficacy and Safety Evaluation of Vandetanib in the Treatment of Medullary Thyroid Cancer.

The aim of the work was to systematically evaluate the efficacy and safety of Vandetanib in the treatment of advanced medullary thyroid carcinoma (MTC). MeSH entries to search for randomized controlled trials and clinical research literature on the application of Vandetanib in the treatment of medullary thyroid cancer from PubMed, Chinese national knowledge infrastructure (CNKI), and Web of Science databases since their establishment until March 2023 were used. In terms of efficacy, the analysis results showed that Vandetanib had a significantly higher objective response rate compared to the control group using placebo (OR=2.13, 95% CI: 1.38, 3.29). In terms of side effects, Vandetanib significantly increases the incidence of hypertension, rash, and diarrhea, and has statistical significance (p+<+0.05). Vandetanib has a better therapeutic effect on MTC, but it also increases the incidence of hypertension, rash, and diarrhea. Attention should be paid to the relief of side effects when using it.

Low-Intensity Resistance Exercise Based on Myofascial Chains Alters the Lower-Limb Tension and Improves Health Status in Female Individuals With Knee Osteoarthritis.

BACKGROUND: Low-intensity resistance exercise therapy (LIRET) based on myofascial chains, applied to both affected and nonlocal joints, is an effective method for knee osteoarthritis (OA) rehabilitation. This study applied LIRET in a comparison of prevalues and postvalues of lower-limb tension in female patients with knee OA and asymptomatic participants. METHODS: Twenty-four female participants with knee OA and 20 asymptomatic women took part in a 3-month long application of LIRET. Participants' ankle passive torque and ankle range of motion in the sagittal plane were assessed with an isokinetic dynamometer. The collected values were used to estimate the sagittal-plane lower-limb tension. RESULTS: Compared with the asymptomatic group, participants with knee OA presented decreased maximum ankle dorsiflexion (P < .001), decreased ankle plantar flexion range (P = .023), ankle resting position more inclined to dorsiflexion (P = .017), increased ankle dorsiflexion stiffness (P = .005), and lower ankle plantar flexion stiffness (P = .034). After exercise intervention, the knee OA group self-reported less knee pain (P < .001), improved physical function (P < .001), increased maximum dorsiflexion (P = .021), and increased plantar flexion range (P < .001). While plantar flexion stiffness increased (P = .037), dorsiflexion stiffness decreased (P = .015) and ankle resting position moved toward dorsiflexion (P = .002). Results suggest possible decreased anterior leg tension and possible increased posterior leg tension in patients with knee OA. CONCLUSIONS: The results supported that knee OA patients present imbalanced myofascial tension of lower limbs. LIRET based on myofascial chains appears to decrease pain, and stiffness, and improve physical function of patients with knee OA and change their lower-limb tension.

[Changes of perimysial junctional plates induced by excessive eccentric training and the effects of acupuncture intervention].

This study aimed to investigate the effects of acupuncture intervention on excessive eccentric training-induced changes of perimysial junctional plates (PJPs) domain. Thirty healthy male Wistar rats were randomly assigned to 5 groups: control group, four-week training group, four-week training + 1-week recovery group and four-week training + 1-week acupuncture group. Rats were subjected to continuous excessive eccentric training for 4 weeks (incline -16°, speed 16-20 m/min, 60-90 min/d, 5 day per week), and then were subjected to one-week spontaneous recovery or one-week recovery with acupuncture intervention (a piece of filiform needle for 4 min every day). The PJPs domain changes were observed under transmission electron microscopy, and the perimysial collagen network structural changes were examined by scanning electron microscopy with or without a digestion technique (NaOH). The following results were obtained: (1) Compared with control group, PJPs domain of four-week training group showed excessive shortening of sarcomere (P < 0.001), serious damage of sarcomere structure, and altered mitochondria morphology in intermyofibria and subsarcolemma; 54% degradation of sarcolemma, and increased number of caveolae (P < 0.01); reduced number of PJPs (P < 0.001). (2) In comparison with four-week training group, PJPs domain was slightly changed in four-week training + 1-week recovery group, i.e., partial recovery of sarcomere length and structure (accounting for 85.23% of control group), and recovery of intermyofibrial and subsarcolemmal mitochondria morphology; decreased sarcolemmal degradation (P < 0.001), and increased number of caveolae (P < 0.05); increased PJPs number (P < 0.001). (3) PJPs domain changed in four-week training + 1-week acupuncture group compared with four-week training + 1-week recovery group, which were substantial recovery of sarcomere length (accounting for 94.51% of control group), increased subsarcolemmal mitochondrial fusion (P < 0.001), decreased caveolae number (P < 0.001), and decreased PJPs number (P < 0.001). The results indicated that excessive eccentric training resulted in excessively reduced number of PJPs with altered PJPs domain homeostasis, thus impeding the adaptability to eccentric training. After 1 week of natural recovery, the number of PJPs was excessively increased, hindering muscle damage repair. Acupuncture intervention helped to recover PJPs number and PJPs domain homeostasis, thus significantly relieving overuse injuries.

Computer tomography imaging findings of adrenal cavernous hemangiomas: a report of 10 cases.

BACKGROUND: Cavernous hemangiomas (CHs) of the adrenal gland are extremely rare. To date, only a few studies of adrenal CH imaging have been reported. PURPOSE: To analyze the computed tomography (CT) imaging findings of adrenal CHs. MATERIAL AND METHODS: Ten cases of adrenal CHs confirmed by a histopathological examination were retrospectively analyzed. All of the patients had undergone unenhanced and enhanced CT examinations, and eight had also undergone multiphase CT enhancement examinations. CT characteristics, including shape, size, margin, attenuation, and enhancement patterns, were analyzed. RESULTS: The study included six women and four men with a mean age of 49.2 years (age range, 25-62 years) and no signs of abnormal endocrine activity. The unenhanced CTs showed well-defined, heterogeneous (n = 8) or homogeneous (n = 2) density masses with scattered (n = 8) or spread calcifications (n = 2) in six tumors. In the contrast-enhanced CTs, seven tumors appeared to be marked with heterogeneous enhancement, whereas three cases exhibited no obvious enhancement. The evaluation of the pattern of dynamic enhancement in eight patients revealed that the tumors showed early peripheral enhancement (n = 4), early central enhancement (n = 1), and mixed enhancement (n = 1) with progressive partial filling-in, and no obvious enhancement in any phases (n = 2). CONCLUSION: Adrenal CHs should be included in the differential diagnosis when an adrenal neoplasm is incidentally found and appears as a well-defined, heterogeneous mass with calcifications and various enhancement patterns, including heterogeneous enhancement with characteristic progressive partial filling-in, as well as lack of enhancement in any phase.

Primary renal synovial sarcoma: computed tomography imaging findings.

BACKGROUND: A synovial sarcoma arising from the kidney is extremely rare. To date, few data are available on their radiological features. PURPOSE: To identify the computer tomography (CT) imaging findings of primary renal synovial sarcomas (PRSSs). MATERIAL AND METHODS: Five cases of PRSS confirmed by histopathological and cytogenetic studies were retrospectively analyzed. All patients had undergone unenhanced and multiphase enhanced CT examinations (one patient underwent CT twice). The CT characteristics, including shape, size, margin, attenuation, and enhancement pattern after intravenous contrast medium injection, were analyzed. RESULTS: The study involved two female and three male patients (mean age, 27.4 years; range, 15-43 years). Unenhanced CT showed completely or partly well-defined masses, with heterogeneous (n = 5) or homogeneous (n = 1) patchy low density. On multiphase contrast-enhanced CT, in five of the six CT examinations, the tumors appeared as solid-cystic masses with cyst walls or pseudo-capsules, and demonstrated moderately heterogeneous (n = 5) and/or septate enhancement (n = 2), with a "rapid wash-in and slow wash-out" pattern of enhancement in the solid component. Only one tumor showed a simple cyst appearance and developed an irregular, intratumoral, septate soft density 8 months later. A renal vein and inferior vena cava thrombus was noticed in one patient, while lymphadenopathy was not observed in any patient. CONCLUSION: PRSS should be included in the differential diagnosis when an adolescent or young adult presents with a renal neoplasm appearing as a solid-cystic mass with well-defined borders, a cystic wall or pseudo-capsule, heterogeneous or septate enhancement, a "rapid wash-in and slow wash-out" pattern of enhancement in the solid component, and no sign of lymphadenopathy.

Abnormal regional homogeneity of resting-state brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy.

BACKGROUND: Many studies have reported that cognitive deficits exist in cirrhotic patients without overt hepatic encephalopathy (OHE). However, the neurobiological mechanisms underlying these deficits are still not fully understood. AIM: To investigate regional activity abnormalities in patients with hepatitis B virus-related cirrhosis (HBV-RC) without OHE using resting-state functional MRI (Rs-fMRI), and to examine the relationship between regional activity abnormalities and impaired cognition. METHODS: A newly reported regional homogeneity (ReHo) approach was used to compare the local synchronization of Rs-fMRI signals in 32 patients with HBV-RC without OHE and 32 well-matched healthy controls. Cognition was measured in all patients using psychometric hepatic encephalopathy score (PHES) tests, and the relationship between ReHo variation and PHES was analysed. RESULTS: Relative to healthy controls, the cirrhosis group showed high ReHo in the prefrontal cortex, and widespread low ReHo in visual association areas (left lingual gyrus, middle temporal gyrus and right middle occipital gyrus), motor association areas (bilateral precentral gyrus and paracentral lobule) and the bilateral precuneus. Correlation analysis of the mean ReHo values in different brain areas and PHES in cirrhotic patients revealed a significantly positive correlation in the left lingual gyrus (r = 0.352; P = 0.048), right middle occipital gyrus (r = 0.453; P = 0.009) and bilateral precentral gyrus (left: r = 0.436, P = 0.013; right: r = 0.582, P < 0.001), paracentral lobule (r = 0.485; P = 0.005) and precuneus (r = 0.468; P = 0.007). CONCLUSIONS: Our results provide information on the pathophysiological mechanisms underlying cognitive alterations in cirrhotic patients and demonstrate the feasibility of using Rs-fMRI with ReHo analysis as a noninvasive modality with which to detect the progression of cognitive changes in cirrhotic patients.

Abnormal baseline brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy revealed by resting-state functional MRI.

Neurocognitive dysfunction of varying degrees is common in patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE). However, the neurobiological mechanisms underlying these dysfunctions are not well understood. We sought to identify changes in the neural activity of patients with HBV-RC without OHE in the resting state by using the amplitude of low-frequency fluctuation (ALFF) method and to determine whether these changes were related to impaired cognition. Resting-state functional MRI data from 30 patients with HBV-RC and 30 healthy controls matched for age, sex, and years of education were compared to determine any differences in the ALFF between the two groups. Cognition was measured with the psychometric hepatic encephalopathy score (PHES), and the relationship between these scores and ALFF variation was assessed. Compared with controls, patients showed widespread lower standardized ALFF (mALFF) values in visual association areas (bilateral lingual gyrus, middle occipital gyrus, and left inferior temporal gyrus), motor-related areas (bilateral precentral gyrus, paracentral lobule, and right postcentral gyrus), and the default mode network (bilateral cuneus/precuneus and inferior parietal lobule). Higher mALFF values were found in the bilateral orbital gyrus/rectal gyrus. In patients, mALFF values were significantly positive correlated with the PHES in the right middle occipital gyrus and bilateral precentral gyrus. Our findings of resting-state abnormalities in patients with HBV-RC without OHE suggest that neurocognitive dysfunction in patients with HBV-RC without OHE may be caused by abnormal neural activity in multiple brain regions.

Factors associated with severe depressive symptoms among Chinese secondary school students in Hong Kong: a large cross-sectional survey.

Background: Many adolescents were reported to have severe depressive symptoms, and a careful assessment of its correlates is essential for prevention and intervention programs. This study aimed to gain insight into the prevalence of severe depressive symptoms and its association with factors at four levels (individual, relationship, school and society) in a large sample of Hong Kong Chinese secondary school students. Methods: Secondary school students from Secondary 1 through 7 were selected as participants using a cluster random sampling method. A questionnaire including inventories measuring 24 factors at the four levels (six individual factors, 11 relationship factors, three school factors, and four society factors) was completed by 8,963 participants (56.3% female) with a mean age of 15.1 (SD = 1.8) years. Students with a score of ≥15 on the Patient Health Questionnaire were defined as having severe depressive symptoms. The association between severe depressive symptoms and correlates were examined by t-test and χ2 test. Logistic regression models using a hierarchical approach then examined the individual contribution of these 24 factors to severe depressive symptoms with the control of other factors in the model. Results: 7.4% of the students have severe depressive symptoms. Twenty-two of the 24 factors were significantly associated with severe depressive symptoms in bivariate analyses. In the logistic regression, 11 factors (three individual factors: age, self-esteem and self-mastery; six relationship factors: tobacco use, alcohol drinking, drug use, paternal psychological control, dinner with parents, and perceived social support from friends; one school factor: felt pressure from homework; and one society factor: number of sibling) were statistically significant. Felt pressure from homework, alcohol drinking, and perceived social support from friends were the strongest correlates of severe depressive symptoms. Conclusion: The prevalence of self-reported severe depressive symptoms in Hong Kong Chinese secondary school students was high, and the identification of multiple associated factors at the four levels simultaneously provides a knowledge basis for the development of a comprehensive, multivariate model of factors influencing severe depressive symptoms in Chinese secondary school students. The factors identified in the present study may be helpful when designing and implementing preventive intervention programs.

CDK12 Promotes the Proliferation, Migration, and Angiogenesis of Gastric Carcinoma via Activating the PI3K/AKT/mTOR Signaling Pathway.

Cyclin-dependent kinase 12 (CDK12) has been found to regulate tumor progression. However, its function in gastric carcinoma (GC) remains controversial. This work aimed to explore the exact effect of CDK12 on GC progression. We detected the expression of CDK12 in GC cells and normal gastric mucosal epithelial cells. Then CDK12 function on GC cell proliferation, migration, and angiogenesis was researched by colony formation experiment, Transwell experiment, and angiogenesis assay. Moreover, CDK12 effect on the PI3K/AKT/mTOR pathway activity was explored by western blot. Further, we used LY294002 (10 µM) to treat GC cells to verify whether CDK12 regulates GC progression by activating the PI3K/AKT/mTOR pathway. Additionally, CDK12 effect on the expression of prognostic factors of GC was detected by western blot, including alkaline phosphatase (ALP) and Ki67. Quantitative real-time polymerase chain reaction and western blot were utilized to evaluate the expression of mRNAs and proteins. As a result, CDK12 was upregulated in GC cells. CDK12 overexpression facilitated the proliferation, migration, and angiogenesis of GC cells. However, CDK12 silencing showed an opposite result. CDK12 overexpression activated the PI3K/AKT/mTOR pathway, but CDK12 silencing inactivated it in GC cells. The blockage of the PI3K/AKT/mTOR pathway induced by LY294002 treatment counteracted the promotion of CDK12 on the proliferation, migration, and angiogenesis of GC. Further, CDK12 silencing suppressed the expression of ALP and Ki67 proteins in GC cells. Taken together, CDK12 promotes the proliferation, migration, and angiogenesis of GC by activating the PI3K/AKT/mTOR pathway. It may be a novel target for GC treatment.

[Evaluation of gefitinib plus radiotherapy in non-small-cell lung cancer patients with brain metastases].

OBJECTIVE: To evaluate the efficacies of gefitinib plus radiotherapy in the treatment of brain metastases in non-small-cell lung carcinoma (NSCLC) patients. METHODS: A retrospective analysis was conducted for 161 NSCLC patients with brain metastases treated in Xinqiao Hospital from January 2001 to January 2010. And 38 patients aged 38 - 77 years old received the combined regimen of gefitinib plus radiotherapy. It consisted of synchronically practicing general or stereotactic brain radiotherapy and an oral intake of gefitinib (250 mg, QD for at least 8 consecutive weeks). The efficacies and toxicity were evaluated at Week 12 after the initial treatment. A total of 123 patients aged 37 - 76 years old undergoing whole brain or stereotactic radiotherapy were used as control. χ(2) test between two groups was carried out to evaluate the objective response rate (ORR), disease control rate (DCR), brain metastasis related symptoms and III-IV degree of toxicity. Non-parametric rank tests were performed to compare the U.S. Eastern Cooperative Oncology Group (ECOG) performance status score between two groups. RESULTS: In the combination therapy group, the levels of ORR and DCR were significantly higher than those in the conventional treatment group (31.6%, 78.9% vs 15.4%, 60.2%). The differences were statistically significant (χ(2) = 4.859, P = 0.027 and χ(2) = 4.479, P = 0.034); significant difference existed in brain metastasis-related symptoms between two groups (χ(2) = 4.612, P = 0.037); the ECOG scores were evaluated in the combination therapy group. And they were as follows: 0 - 1 (n = 18), 2 (n = 11), 3 - 4 (n = 9) at pre-treatment vs 0 - 1 (n = 27), 2 (n = 6), 3 - 4 (n = 5) at post-treatment. The ECOG score significantly improved after treatment (Z = -2.012, P = 0.044). Regarding the III-IV degree of toxicity, the combination therapy group had 4 patients with acne-like rash and it was significantly higher than that in the conventional therapy group (n = 0) (P = 0.003). But no difference existed in the occurrence of fatigue, nausea, vomiting, diarrhea and myelosuppression. CONCLUSION: The combined regimen of gefitinib plus radiotherapy can improve the therapeutic efficacies of brain metastases and enhance the quality-of-life in NSCLC patients, side effects are tolerable.

Amplitude low-frequency oscillation abnormalities in the heroin users: a resting state fMRI study.

Functional neuroimaging studies have revealed abnormal functional organization of the heroin users' brain, including reward circuit, cognitive control circuit, memory circuit, motivation and salience evaluation circuits and so on. In the current study, we aimed to explore the functional changes in the regional brain of heroin users using the amplitude of low-frequency oscillations in the Blood Oxygenation Level Dependent (BOLD) signals. With fMRI data acquired during resting state from 24 chronic heroin users (all subjects were being treated with methadone) and 24 non-addicted controls, we investigated addiction related altered in the amplitude low-frequency fluctuate (ALFF) between the two groups. Compared with controls, we found that heroin addicts had decreased ALFF in the bilateral dorsal anterior cingulate cortex (dACC), bilateral medial orbit frontal cortex (mOFC), left dorsal lateral prefrontal cortex (dlPFC), left middle temporal gyrus, left inferior temporal gyrus, posterior cingulate cortex and left cuneus as well as increased ALFF in the bilateral angular gyrus, bilateral precuneus, bilateral supramarginal gyrus, left post cingulate cortex and left middle frontal gyrus. Moreover, we also found that the increased ALFF in the bilateral parietal lobe had a significantly positive correlation with the methadone does, thus we inferred that the reduced ALFF may due to heroin consumption, nevertheless, the increased ALFF in the bilateral parietal lobe may have resulted from the methadone treatment. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of heroin addicts.

Regional homogeneity changes in heroin-dependent individuals: resting-state functional MR imaging study.

PURPOSE: To identify heroin-related modulations of neural activity in the resting state in heroin-dependent individuals (HDIs) by using resting-state functional magnetic resonance (MR) imaging and a regional homogeneity method and to investigate whether these changes of neural activity can be related to duration of heroin use and to decision-making deficits in HDIs. MATERIALS AND METHODS: This prospective study was approved by the appropriate ethics committee, and written informed consent was obtained from each participant. Thirty-one HDIs receiving methadone-maintained treatment and 24 control subjects participated. Resting-state functional MR imaging was performed by using a gradient-echo echo-planar imaging sequence. Regional homogeneity was calculated by using software. Voxel-based analysis of the regional homogeneity maps between control and HDI groups was performed with two-sample t tests by using software. Statistical maps were set at P less than .05 and were corrected for multiple comparisons. The Iowa gambling task (IGT) was used to assess participant decision making during uncertainty. Abnormal clusters revealed by group comparison were extracted and correlated with behavioral performance at the IGT and with duration of heroin use. RESULTS: Regional homogeneity was diminished in the bilateral medial orbitofrontal cortex (OFC), bilateral dorsal medial thalamus, bilateral cuneus, and lingual gyrus in HDIs compared with control subjects. There were negative correlations between mean regional homogeneity in the medial OFC, bilateral cuneus, and lingual gyrus and duration of heroin use. There was a positive correlation between mean regional homogeneity in the medial OFC and performance level at the IGT. CONCLUSION: The present study reveals resting-state abnormalities in HDIs that may lead to further improvement of the understanding of the neural substrates of cognitive impairment in HDIs.

Nanoparticles-EPS corona increases the accumulation of heavy metals and biotoxicity of nanoparticles.

Microbial extracellular polymeric substances (EPS) coating nanoparticles (NPs) surface can form NPs-EPS corona, which significantly affect the adsorption of NPs to toxic substances and alter the ecotoxicological effect of NPs. In this work, the EPS coronas on TiO2 NPs (TNPs) and CeO2 NPs (CNPs) were characterized and the adsorption characteristics of NPs with and without EPS corona to five heavy metals were investigated in single-metal and multiple-metal systems. The results of spectral analysis showed that NPs-EPS corona exhibited new crystalline phases and abundant functional groups. Moreover, 42 and 13 proteins were identified in the TNPs-EPS and CNPs-EPS coronas, respectively. The rates of Cd2+, Pb2+, Cu2+, Ni2+ and Ag+ adsorption by NPs-EPS corona increased to values that were 6.7-7.6, 4.4-5.1, 4.2-5.5, 3.9-4.9 and 8.5-8.8 times those of NPs without EPS corona, respectively, in single-metal system. NPs-EPS coronas are effective in absorbing Ag+, Pb2+ and Cu2+ compared with Cd2+and Ni2+ in multiple metal adsorption. These results indicated that NPs-EPS corona effectively adsorb and remove heavy metals by forming NPs-EPS-metal complexes and inducing precipitation. However, NPs-EPS corona can enhance the toxicity of NPs by accumulating highly-toxic heavy metals in aquatic environments.

XMD-17-51 Inhibits DCLK1 Kinase and Prevents Lung Cancer Progression.

Doublecortin-like kinase 1 (DCLK1) is a cancer stem cell marker that is highly expressed in various types of human cancer, and a protein kinase target for cancer therapy that is attracting increasing interest. However, no drug candidates targeting DCLK1 kinase have been developed in clinical trials to date. XMD-17-51 was found herein to possess DCLK1 kinase inhibitory activities by cell-free enzymatic assay. In non-small cell lung carcinoma (NSCLC) cells, XMD-17-51 inhibited DCLK1 and cell proliferation, while DCLK1 overexpression impaired the anti-proliferative activity of XMD-17-51 in A549 cell lines. Consequently, XMD-17-51 decreased Snail-1 and zinc-finger-enhancer binding protein 1 protein levels, but increased those of E-cadherin, indicating that XMD-17-51 reduces epithelial-mesenchymal transition (EMT). Furthermore, sphere formation efficiency was significantly decreased upon XMD-17-51 treatment, and XMD-17-51 reduced the expression of stemness markers such as ß-catenin, and pluripotency factors such as SOX2, NANOG and OCT4. However, the percentage of ALDH+ cells was increased significantly following treatment with XMD-17-51 in A549 cells, possibly due to EMT inhibition. In combination, the present data indicated that XMD-17-51 inhibited DCLK1 kinase activity in a cell-free assay with an IC50 of 14.64 nM, and decreased DCLK1 protein levels, cell proliferation, EMT and stemness in NSCLC cell lines. XMD-17-51 has the potential to be a candidate drug for lung cancer therapy.

[Heterogeneity of angioarchitecture and their hemodynamic changes in benign and malignant breast tumors].

OBJECTIVE: To explore the differences between the angioarchitecture, hemodynamics, ultrastructure of neovasculr endothelial cells, and vascular distribution in different perfusion regions in benign and malignant breast tumors. METHODS: 30 cases of breast carcinoma (33 lesions) and 30 cases of breast fibroadenoma (34 lesions) were examined by contrast enhanced microvascular imaging (MVI), and perfusion indexes were collected both inside and at the margin of each focus according to time-intensity quantitative analysis, including peak intensity (PI), area under the curve (AUC), time to peak (TTP) and wash-out time (WOT). The ultrastructure of neovascular endothelial cells was examined by transmission electron microscopy. The expression of CD34, VEGF, Flk-1/KDR in both two groups were detected by immuhistochemistry. RESULTS: Significant differences were found between the two groups characterized with filling defect, vascular distortion, dilatation and uneven enhancement. Most of the curves of malignant group (87.9%, 29/33) ascended rapidly and dropped slowly while those of the benign group (79.4%, 27/34) ascended slowly and dropped rapidly. The AUC and WOT of malignant tumor group were significantly higher than those of benign group, while the PI and TTP had statistically no significant difference. In the malignant tumor group, PI, AUC and WOT collected from the margin of foci were significantly different from those collected inside the foci, however, there was no significant difference in the benign group. The margin of foci was characterized with dilated and distorted vessels, and the center of the foci was occupied by narrow or occluded blood vessels, sometimes with contracted endothelial cells and pericytes. Abundant microvascular areas located at the margin of foci. The ultrastructure of endothelial cells in the newly formed blood vessels of malignant group showed strong ability to divide, which was different from normal endothelium cells. CONCLUSION: The perfusion pattern, mode of time-intensity curve, mean perfusion parameter and variation of regional perfusion parameters provide a valuable diagnostic basis in distinguishing benign and malignant breast tumors. The density, morphology, distribution, structure and function of newly formed microvessels in tumor foci are also crucial factors when tumors are assessed by imaging examination.

[Evaluation of angiogenesis in the tumorigenesis and progression of breast cancer].

OBJECTIVES: To investigate the expression of CD34, vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR in precancerous lesion, atypical hyperplasia (AH) and infiltrating carcinoma of breast cancer and to explore the correlation between angiogenesis abnormality and the tumor progression. METHODS: One hundred and sixty cases of resected tissues from breast cancer patients were enrolled in the study and were divided into 5 groups: 30 cases as normal controls, 30 cases with simple hyperplasia, 30 cases with AH, 20 cases with intraductal carcinoma in situ and 50 cases with infiltrating ductal carcinoma. The expression of CD34, VEGF and its receptor, Flk-1/KDR in those tissues were determined with immunohistochemical techniques. The micro vascular density (MVD) in those tissues was determined with the expression of CD34. RESULTS: The expression level of CD34, VEGF and Flk-1/KDR were different among the groups, with the highest expression in the infiltrating ductal carcinoma group. With the progression of breast cancer, the major indexes showed no significant changes in the early stage of progression, but the expression of VEGF and Flk-1/KDR increased significantly from AH stage. Meanwhile, the MVD increased in the same way. There was significant difference between AH and intraductal carcinoma group in the expression of VEGF and Flk-1/KDR (P<0.05), but not in the MVD (P>0.05). CONCLUSIONS: Abnormality in angiogenesis may be an early event in the tumorigenesis of breast cancer. Abnormal expression of VEGF and Flk-1/KDR may be the initiating factor of angiogenesis in the process of breast hyperplasia-AH-breast cancer, it could be the molecular target of early diagnosis and treatment.

The relationship between chronic obstructive pulmonary disease and non-small cell lung cancer in the elderly.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) and NSCLC often coexist and have poor prognoses, but studies investigating the impact of COPD on NSCLC have reported inconsistent findings. The objective of this study was to compare survival between NSCLC patients with and without COPD. METHODS: Medical records were retrospectively collected from 301 elderly patients pathologically diagnosed with NSCLC from the Chinese PLA General Hospital. Ultimately, a total of 200 patients were enrolled in the analysis. The survival rates between the COPD-NSCLC and non-COPD NSCLC were assessed using log-rank and Cox proportional hazard regression analyses. RESULTS: A total of 117 COPD-NSCLC and 93 non-COPD NSCLC patients were enrolled in the analysis. The median overall survival times were 108.5 months in the non-COPD group and 45.0 months in the COPD group (HR: 2.05; 95% CI, 1.36-2.97, P = 0.0004). After 118 patients underwent propensity score matching, the median overall survival times were 100.6 months in the non-COPD group and 51.9 months in the COPD group (HR: 1.59; 95% CI, 1.096-2.64, P = 0.0459). The multivariate analysis showed that presence of COPD (HR 1.619, P = 0.030), old age (HR 1.007, P < 00001), an advanced disease stage (stage Ⅲ HR 5.513, P < 0.0001; stage Ⅳ HR 11.743, P < 0.0001), the squamous cell carcinoma histological subtype (HR 3.106, P < 0.0001), the presence of a cough (HR 2.463, P = 0.001) a higher serum carcinoembryonic antigen level (HR 1.001, P = 0.023) and higher NRL (HR 2.615, P = 0.007) were independent factors that were significantly associated with poorer survival. CONCLUSION: A diagnosis of COPD had significant poorer survival outcomes in NSCLC than that of patients without COPD in this elderly population.

[Effects of different Chinese herbal medicines on biochemical parameters in guinea-pig with pigment gallstones].

OBJECTIVE: To observe the effects of Qingdan Capsule (QDC) and Yanggan Lidan Granule (YGLDG), two kinds of compound traditional Chinese herbal medicines, on biochemical parameters in guinea-pigs with pigment gallstones. METHODS: An animal model of pigment gallstones was established in male guinea-pigs by hypodermic injection of lincomycin. The guinea-pigs were randomly divided into blank control group, untreated group, QDC group and YGLDG group. There were 8 guinea-pigs in each group. After ten-day treatment, animals were sacrificed and sampled to calculate the rate of stone formation, total bilirubin (TB), unconjugated bilirubin (UCB) and Ca2+ density in bile of the four groups. RESULTS: In comparison with the untreated group, the rates of stone formation in the QDC and YGLDG groups were significantly decreased (P<0.01). TBIL, UCB and Ca2+ content of bile in both QDC and YGLD groups was also significantly decreased (P<0.05, P<0.01). CONCLUSION: QDC and YGLD have good effects on biochemical changes of animal model of pigment gallstone in reversing the lithogenesity of bile by reducing the content of TB, UCB and Ca2+, hence resulting in clinical treatment and prevention of pigment gallstone disease.

[Effects of Shengqing Capsule on biochemical parameters in mice with cholesterol gallstone].

OBJECTIVE: To observe the effects of Shengqing Capsule (SQC), a compound of traditional Chinese herbal medicine, on biochemical parameters in C57BL/6J mice with cholesterol gallstone. METHODS: Thirty-eight C57BL/6J mice were randomly divided into normal control group (n=10), untreated group (n=15) and SQC group (n=13). Cholesterol gallstone was induced in mice of the latter two groups by feeding high cholesterol diet. Mice in the SQC group were intragastricly administered SQC 0.22 g/(kg.d). After 8-week treatment, animals were sacrificed and sampled to calculate the incidences of stone formation. The contents of serum cholesterols and Ca(2+), and the malonaldehyde (MDA) content and superoxide dismutase (SOD) activity in liver tissues were detected. RESULTS: The incidences of stone formation were 73.33% in untreated group, 0% in normal control group, and 23.08% in the SQC group. And the INCIDENCE in untreated group was significantly higher than those in the normal control group and the SQC group (P<0.01). Contents of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the SQC group were lower than that in the untreated group (P<0.01), and high-density lipoprotein cholesterol (HDL-C) in the SQC group was higher than that in the untreated group (P<0.01). SQC could increase the SOD activity and decrease the MDA content in liver tissues, showing significant differences as compared with those in the untreated group (P<0.05). CONCLUSION: SQC can decrease the incidence of stone formation and improve the biochemical parameters, which may be one of the mechanisms in the treatment and prevention of cholesterol gallstone disease.