[Coronary CT angiography derived fractional flow reserve: the consideration and practice of functional evaluation for cerebral arterial diseases].

Cerebrovascular disease is a significant global public health concern, despite the diagnosis and treatment of stroke has made great progress in recent years, however, its mainly guided by anatomical indicators, which still needs to be further improved, and there is an urgent need to explore a more accurate and comprehensive functional imaging assessment method. Rapid development of coronary CT angiography derived fractional flow reserve (CT-FFR) has become an important technique for noninvasive evaluation of coronary artery disease, and these successful application experiences inspiried neurologists to explore the functional evaluation technique of cerebral arteries and demonstrated broad application prospects. In this paper, by analyzing and comparing the coronary CT-FFR technology, the progress, existing problems and possible solutions of the functional evaluation for cerebral arterial stenosis are discussed from the aspects of coronary CT-FFR study, cerebral artery functional evaluation study, and the comparison and consideration of cerebral arterial and coronary CT-FFR.

[Risk factors associated with acute kidney injury caused by pesticide poisoning].

Objective: To analyze the clinical characteristics of pesticide poisoning patients and explore the risk factors of acute kidney injury (AKI) . Methods: In September 2020, the clinical data of 155 patients with pesticide poisoning in the department of nephropathy, the Affiliated Hospital of Southwest Medical University from September 2018 to August 2020 were retrospectively analyzed. The patients were divided into AKI group (44 cases) and non AKI group (111 cases) according to the occurrence of AKI. The clinical characteristics, organ or system involvement and auxiliary examination results of the two groups were analyzed. Logistic regression was used to analyze the risk factors of AKI in patients with pesticide poisoning. Results: The types of pesticides causing poisoning mainly included herbicides, insecticides and biochemical pesticides. Compared with non AKI group, patients in AKI group had higher proportion of blood purification treatment and ICU monitoring treatment (P<0.05) , and were more likely to be complicated with acute respiratory failure, pulmonary fibrosis, myocardial injury, multiple organ dysfunction syndrome (MODS) , acute pancreatitis and coagulation abnormalities (P<0.05) . The mortality of AKI group (18.2%, 8/14) was significantly higher than that of non AKI group (0.9%, 1/111) (P<0.05) . Univariate analysis showed that the time from poisoning to treatment > 6 h, high WBC count, neutrophil count, alanine aminotransferase, aspartate aminotransferase, high sensitive troponin T, myoglobin and creatine kinase isoenzyme were the risk factors of AKI in patients with pesticide poisoning (P<0.05) . Multivariate logistic regression analysis showed that the time from poisoning to treatment >6 h was an independent risk factor for AKI in patients with pesticide poisoning (P<0.05) . Conclusion: The mortality of AKI secondary to pesticide poisoning is high. Attention should be paid to the time from poisoning to treatment, inflammatory state and changes of liver and myocardial function.

MiR-492 exerts tumor-promoting function in prostate cancer through repressing SOCS2 expression.

OBJECTIVE: MiRNAs have been verified to play a role in the development and progression of prostate cancer (PCa). However, the role of miR-492 in PCa has not been mentioned. We aim to detect the expression of miR-492 in PCa and explore its underlying mechanism. PATIENTS AND METHODS: The relative expression of miR-492 in PCa tissue samples to normal prostate tissues was detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The level of miR-492 in PCa-derived cell lines compared with the normal prostate cell line was also measured. Cell counting kit-8 (CCK-8) and colony formation assays were employed to investigate the cell proliferation ability. Transwell assay and wound-healing assays were utilized to explore the cell invasion and migration abilities. Luciferase assay and Western blot were utilized to explore the underlying mechanism of miR-492 in PCa cells. RESULTS: MiR-492 expressed significantly higher in PCa tissues than that in the normal tissues. Its expression level was also over-expressed in PCa cells compared with that in the normal cells. The up-regulation of miR-492 promoted the growth, invasion, and migration of the cells, while down-regulation had the opposite effects. SOCS2 was identified as a potential target for miR-492 in PCa. Silencing of SOCS2 could neutralize the inhibitory function of miR-492 inhibitor in PCa cells. CONCLUSIONS: This study demonstrated that miR-492 was over-expressed in PCa and exerted tumor-promoting function in PCa cells via repressing SOCS2 expression. This might provide a new sight for future accurate therapy for PCa.

A gain-of-function mutation in TNFRSF13B is a candidate for predisposition to familial or sporadic immune thrombocytopenia.

Essentials Positive family histories suggest the existence of hereditary immune thrombocytopenia (ITP). The predisposing gene for familial ITP was screened in two familial ITP patients. The G76S mutation on TNFRSF13B led to immune dysfunction and induced megakaryocyte apoptosis. The G76S mutation on TNFRSF13B is a gain-of-function mutation and a predisposing variant for ITP. SUMMARY: Background Most immune thrombocytopenia (ITP) is sporadic but a positive family history of ITP in some patients suggests that hereditary forms exist. Because of the rarity of familial ITP families available for study and the heterogeneity of sporadic ITP, family linkage analysis or genome-wide association studies are limited. Objectives Based on one ITP pedigree, we try to identify the predisposing gene in familial or sporadic ITP and reveal the way in which it causes thrombocytopenia. Methods Gene expression profiling analysis and whole-exome sequencing were performed on samples from family members with ITP, sporadic ITP cases and healthy individuals. We also evaluated the influence of potential pathogenic mutation on immune function and megakaryocyte apoptosis. Results Whole-exome sequencing identified a potential pathologic p.G76S heterozygous mutation on the TNFRSF13B gene in familial ITP patients. ITP patients harboring the G76S mutation displayed an upregulated 'cytokine-cytokine receptor interaction' signal, increased serum TNFα, IL-17α, IFNγ and BAFF levels, and enhanced binding capacity of APRIL ligand to B cells. Additionally, Epstein-Barr virus (EBV)-transformed B cells with the G76S mutation could induce human megakaryocyte line (Meg-01) apoptosis significantly. Conclusion p.G76S mutation on the TNFRSF13B gene is responsible for ITP, and is a genetic predisposing factor for familial or sporadic ITP.

KRT19 directly interacts with ß-catenin/RAC1 complex to regulate NUMB-dependent NOTCH signaling pathway and breast cancer properties.

Studies have reported that interactions between keratins (KRTs) and other proteins initiate signaling cascades that regulate cell migration, invasion, and metastasis. In the current study, we found that expression of KRT19 was specifically high in breast cancers and significantly correlated with their invasiveness. Moreover, knockdown of KRT19 led to increased proliferation, migration, invasion, drug resistance, and sphere formation in breast cancer cells via an upregulated NOTCH signaling pathway. This was owing to reduced expression of NUMB, an inhibitory protein of the NOTCH signaling pathway. In addition, we found that KRT19 interacts with ß-catenin/RAC1 complex and enhances the nuclear translocation of ß-catenin. Concordantly, knockdown of KRT19 suppressed the nuclear translocation of ß-catenin as well as ß-catenin-mediated NUMB expression. Furthermore, modulation of KRT19-mediated regulation of NUMB and NOTCH1 expression led to the repression of the cancer stem cell properties of breast cancer patient-derived CD133high/CXCR4high/ALDH1high cancer stem-like cells (CSLCs), which showed very low KRT19 and high NOTCH1 expression. Taken together, our study suggests a novel function for KRT19 in the regulation of nuclear import of the ß-catenin/RAC1 complex, thus modulating the NUMB-dependent NOTCH signaling pathway in breast cancers and CSLCs, which might bear potential clinical implications for cancer or CSLC treatment.

[Finite element analysis of different load mode on tooth movement for space closure in patient with bimaxillary protrusion].

OBJECTIVE: To investigate the stress distribution on the maxillary anterior teeth retracted with sliding mechanics and micro-implant anchorage using different retraction hook heights and positions. METHODS: DICOM image data including maxilla and upper teeth were obtained with cone-beam CT. The three-dimensional finite element model was constructed using Mimics software. Brackets and archwire model were constructed using Creo software. The models were instantiated using Pro/Engineer software. Abaqus software was used to simulate the sliding mechanics by loading 2 N force on 0, 2, 4, 6, 8, 10 mm retraction hooks and three different positions, repectively. Rotation of the occlusal plane, the initial displacement and stress distribution of teeth were analyzed. RESULTS: Lingual rotation of maxillary central incisor(0.021°), gingival movement of the maxillary first molar(0.005 mm), and clockwise rotation of the maxillary occlusal plane(0.012°) were observed when the force application point located at the archwire level (0 mm). In contrast, 0.235° labial rotation of the maxillary central incisor, 0.015 mm occlusal movement of the maxillary first molar, and 0.075° anti-clockwise rotation of the maxillary occlusal plane were observed when the force application point located at the higher level(10 mm retraction hook). The more the force application point was located posteriorly at the archwire level, the less lingual rotation of the maxillary central incisor and the more buccal displacement of maxillary first molar was observed. CONCLUSIONS: Maxillary anterior tooth rotation and retraction, vertical displacement of posterior segment, and rotation of the occlusal plane could be controlled by adjusting the height and position of the retraction hook in space closure using miniscrew and sliding mechanics.

[Prenatal diagnosis of chromosome abnormalities and nine microdeletion syndromes using both traditional karyotyping and BoBs].

OBJECTIVE: To evaluate a new prenatal diagnosis model of chromosomal abnormalities and nine microdeletion syndromes by using both traditional karyotyping and a newly-developed rapid prenatal diagnosis technology, BACs-on-Beads (BoBs) technique. METHODS: From June 2012 to December 2014, 807 pregnant women with high risk after screening or with other indicators, were performed amniocentesis. Traditional karyotyping and BoBs were employed simultaneously for prenatal diagnosis. RESULTS: Thirty-two cases with chromosome aneupoidies were successfully detected both by BoBs and karyotyping, including 18 cases of trisomy 21, 6 cases of trisomy 18, 1 case of trisomy 13, and 7 cases with sex chromosome abnormality. All 8 fetuses with chromosome structural abnormalities detected by karyotyping were missed by BoBs; while BoBs contributed more in detection of five microdeletion syndrome cases, including 3 cases of DiGeorge syndromes (two with microduplication and one with microdeletion), one case of Miller-Dieker syndrome, and one case of Wolf-Hirschhorn syndrome. CONCLUSION: Combined use of traditional karyotyping and BoBs, is a rapid and effective prenatal diagnosis model that may enlarge our horizon on chromosomal diseases and should be widely used in future clinical service.

Molecular diagnosis of HIV and relevant novel technologies in mutation analysis.

HIV infection is one of the major threats to human health due to the lack of relevant vaccine and drugs to cure AIDS. Its early diagnosis is thus important in controlling HIV transmission. Molecular diagnosis of HIV can be performed qualitatively and quantitatively. Currently, molecular diagnosis of HIV infection is only used as a complementary diagnosis although viral load test is used to monitor disease progression and responsiveness to antiviral therapy. To optimize HIV assays, a variety of technological advances, such as the introduction of dUTP/UNG system, real-time detection platform, and coupling of more than one enzyme in molecular identification, have been integrated into new methods. With the development of more reliable HIV assays in the future, the molecular diagnosis of HIV is expected to be accepted as one of the standards in determining whether there is a HIV infection in resource-rich laboratories, which will play a crucial role in reducing HIV transmission.

[Study on mitochondrial ultrastructure, trace elements and correlative factors of gastric mucosa in patients with spleen deficiency syndrome].

Eighty-eight gastropathic patients with Spleen deficiency syndrome by using transmission electron microscope (TEM), X-ray energy disperse analysis system (EDAX), histochemical staining and radioimmuno methods were examined. The authors found that the gastric mucosa cAMP, SOD level, the quantity of mitochondria and its crista, the ratio of diameter between ventricle and cavity of mitochondria and the content of Zn, Cu of mitochondria were reduced in the trend of healthy control group, Spleen Qi deficiency group, Spleen deficiency with Qi stagnation group; chronic superficial gastritis group, chronic atrophic gastritis group, gastric cancer group: complete small intestinal metaplasia group, incomplete small intestinal metaplasia group, complete colonic intestinal metaplasia group, incomplete colonic intestinal metaplasia group (P < 0.05-0.001). While the degeneration rate of mitochondria, the Cu/Zn ratio of mitochondria, the metaplasia rate of gastric, the rate of incomplete colonic intestinal metaplasia and the content of serum LPO were increased in the above turn. It is suggested that the comprehensive effect of the degeneration of mitochondria and the quantitative changes of its correlative factors is the physiopathologic base for inducing Spleen deficiency disease, gastric mucosa metaplasia and canceration. Much attention must be paid in clinic to the cancerization trend of gastric disease with Spleen deficiency syndrome.

[Effect of zhuchun pill on immunity and endocrine function of elderly with kidney-yang deficiency].

After randomly dividing 45 elderly males with Kidney-Yang Deficiency into Zhuchun Pill (ZCP) group and placebo (starch capsule) group by single blind method, and treating them for 3 months, we found that ZCP could greatly improve the main symptoms of Kidney-Yang Deficiency, P < 0.01 by comparison with control group: the 3H-TdR lymphocyte transformation (3H-TdR LCT) rate, level of serum C3, IgA, IgD, IgG & IgM went up (P < 0.01); contents of plasma adrenocortical hormone (ACTH), testosterone (T) and cyclic adenosine monophosphate (cAMP) increased (P < 0.01-0.001): the level of superoxide dismutase (SOD) in serum also increased while lipid peroxide (LPO) in plasma decreased (P < 0.01). But for control group, there were no remarkable changes after treatment, so it revealed that the improvement of Kidney-Yang Deficiency by ZCP is realized through regulating the organism's immunity and endocrine function as well as through scavenging the free radical agents.