[The regulation of APGAT4 on the growth and lenvatinib resistance of hepatocellular carcinoma].

Objective: To investigate the effect of 1-acyl-sn-glycerol-3-phosphate acyltransferaseδ (APGAT4) on the growth and lenvatinib resistance of hepatocellular carcinoma (HCC), and provide novel targets for HCC treatment. Methods: Using the bioinformatics methods to screen out upregulated genes in lenvatinib resistant cell lines from GEO dataset and survival related genes from TCGA dataset. Immumohistochemical staining was used to detect the expression AGPAT4 in HCC tissues, and its correlation with patients' survival. CCK8, EdU, cell cycle, and cell apoptosis assays were used to investigate the impact of role AGPAT4 on the proliferation and lenvatinib reistance of HCC cells. AGPAT4 stable knockdown cell line and subcutaneous nude mouse model were established to test the therapeutic effects of Lenvatinib. Analysis of variance was used to compare the differences between data sets. Results: APGAT4 was the common factor that predicted poor survival and Lenvatinib resistance. The mRNA and protein levels of APGAT4 were significantly upregulated in HCC tissues compared to the para-tumor tissues (P < 0.05). Using siRNA could significantly knocked down the mRNA and protein expression of APGAT4 in HCC cell lines Hep3B and HCCLM3. Compared with the control group, the proliferation ability of HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group was significantly inhibited, and the cell cycle was arrested in G2/M phase (P < 0.05). In addition, compared to the control group, HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group showed significant decrease in the Lenvatinib half maximal inhibitory concentration, and were more sensitive to lenvatinib-induced apoptosis (P < 0.05). In HCC subcutaneous nude mouse model, compared to the control group, the growth of tumor in APGAT4 knockdown group was significantly suppressed, and more apoptosis cells were induced (P < 0.05). Conclusion: APGAT4 promotes the growth and Lenvatinib resistance of HCC, which is a potential target for HCC treatment. Targeting APGAT4 treatment is conducive to inhibit the growth and Lenvatinib resistance of HCC.

Effect of Wnt/ß-catenin signal pathway on of matrix metalloproteinase-7 and vascular endothelial growth factor gene expressions in endometriosis.

PURPOSE: To explore the function of Wnt/ß-catenin signal pathway on promoting the adhesion, invasion, and metastasis of endometriosis tissues by analyzing its effects on the expressions of matrix metalloproteinase-7 (MMP-7) and vascular endothelial growth factor in en- dometriosis. MATERIALS AND METHODS: Endometriosis nude mice models were included. Small RNA interference technology was used to block Wnt/ß-catenin signal pathway. HE staining technique was adopted to observe the difference of pathological morphology among groups. The immunohistochemistry and real-time quantitative PCR were perfonned to analyze the expressions of $-catenin, MMP-7 and VEGF from pro- tein and mRNA levels. RESULTS: Whether the Wnt/ß-catenin signal pathway was blocked or not had little effect on the pathological mor- phology of lesions. The expressions of P-catenin, MMP-7 and VEGF in siRNA group were much lower than those in negative control group and control group (p < 0.05), while there was no statistical significance in the difference of expressions between negative control group and control group (p > 0.05). CONCLUSION: Blocking of Wnt/ß-catenin signal pathway caused the decrease of MMP-7 and VEGF expressions, in- dicating that Wnt/ß-catenin signal pathway plays an important role in the adhesion, invasion, and metastasis of endometriosis tissues.

Protocol for constructing subject-specific biomechanical models of knee joint.

A robust protocol for building subject-specific biomechanical models of the human knee joint is proposed which uses magnetic resonance imaging, motion analysis and force platform data in conjunction with detailed 3D finite element models. The proposed protocol can be used for determining stress and strain distributions and contact kinetics in different knee elements at different body postures during various physical activities. Several examples are provided to highlight the capabilities and potential applications of the proposed protocol. This includes preliminary results on the role of body weight on the stresses and strains induced in the knee articular cartilages and meniscus during single-leg stance and calculations of the induced stresses and ligament forces during the gait cycle.

Computer-controlled acupuncture. Quantification and separation of specific effects.

The effects of acupuncture have been described and handed down empirically for centuries but there are few reports based on objective data. The aim of this study was to provide selective evidence of a specific effect of acupuncture on the brain and the eye using a Doppler ultrasound technique. A transcranial Doppler sonography arrangement was developed to monitor blood flow profiles in the supratrochlear and middle cerebral arteries simultaneously and continuously. Two acupuncture schemas were tested in a randomized cross-over study with 13 patients with ophthalmologic diseases. Applying acupuncture needles to special eye points increased the blood flow velocity in the supratrochlear artery significantly (p < 0.001) compared to the reference interval before acupuncture. In the middle cerebral artery only a minimal, non-significant increase in blood flow velocity was seen. In contrast, acupuncture of points that are held to increase cerebral blood flow velocity increased blood flow velocity in the middle cerebral artery significantly (p < 0.001) while leaving that in the supratrochlear artery unchanged. Specific acupuncture produce specific, reproducible quantifiable effects on blood flow velocity in arteries to the brain and eye.

Ultrasound-monitored effects of acupuncture on brain and eye.

A new transcranial Doppler sonography arrangement was used to monitor blood flow profiles in the supratrochlear and middle cerebral arteries simultaneously and continuously. The technique selectively demonstrated the specific effect of acupuncture on the cranial arteries, in a 25-year-old female with pigmentary retinopathy. Stimulation of points Zanzhu and Yuyao led to a marked increase of blood flow velocity in the supratrochlear artery and to a decrease of flow velocity, in the middle cerebral artery. These acupuncture-induced effects were reproducible even though both arteries originate from the same major vessel.

[Computer-controlled acupuncture. A new construction for simultaneous measurement of blood flow velocity of the supratrochlear and middle cerebral arteries]. / Computerkontrollierte Akupunktur: Eine neue Konstruktion zur simultanen und kontinuierlichen Erfassung der Blutflussgeschwindigkeit in der A. Supratrochlearis und der A. Cerebri media.

Acupuncture has been used for over 5,000 years and a large body of evidence exists. Transcranial Doppler (TCD) ultrasound, introduced more than a decade ago, has evolved into a dynamic, reliable, reproducible and practical diagnostic tool. In this study we describe simultaneous and continuous TCD monitoring of the supratrochlear and middle cerebral arteries in two patients with ophthalmologic diseases undergoing computer-controlled acupuncture (CCA). During eye acupuncture scheme there was a significant increase in the mean bloodflow velocity (vm) of the A. supratrochlearis (+39% patient 1; +15% patient 2; p < 0.001, t-test) in both patients. The effect was still evident after the needles were removed. There was a smaller increase (+4% and +3%; n.s.) of vm in the A. cerebri media. These results suggest that eye acupuncture could have a specific effect on intra- and extracerebral arteries. CCA might improve the quality of acupuncture.

Screen for MAOA mutations in target human groups.

Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-580] described males with an MAO-A deficiency state resulting from a premature stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urine and plasma of affected males, as well as low normal intelligence and apparent difficulty in impulse control, including inappropriate sexual behavior. In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant behavior, as well as normal controls, healthy males, and patients with other diseases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma samples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol (MHPG), a metabolite of norepinephrine which serves as the most sensitive index of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not available, were screened for nucleotide variations in the coding region of the MAOA gene by single-strand conformational polymorphism (SSCP) analysis across all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations disrupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males participating in a sexual disorders clinic (N = 46), as well as control groups (N = 75). These studies indicate that MAOA deficiency states are not common in humans.