Application experience and research progress of different emerging technologies in plastic surgery.

In the diagnosis and treatment of plastic surgery, there are structural processing problems, such as positioning, moving, and reconstructing complex three-dimensional structures. Doctors operate according to their own experience, and the inability to accurately locate these structures is an important problem in plastic surgery. Emerging digital technologies such as virtual reality, augmented reality, and three-dimensional printing are widely used in the medical field, particularly in plastic surgery. This article reviews the development of these three technical concepts, introduces the technical elements and specific applications required in plastic surgery, summarizes the application status of the three technologies in plastic surgery, and summarizes prospects for future development.

A Comparison of Two Molecular Methods for Detecting CALR Mutations in Myeloproliferative Neoplasms.

BACKGROUND: Myeloproliferative neoplasms (MPN) are hematopoietic disorders characterized by abnormal proliferation of the myeloid lineage. Three classic subtypes are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These disorders are well known for their association with the JAK2 V617F mutation, in addition to mutations in MPL exon 10, and JAK2 exon 12. CALR mutations were detected in approximately 20% to 25% of patients with ET and PMF and not in patients with PV. Most CALR mutations were deletions and insertions in exon 9, which caused frameshift mutations. METHODS: This study included 60 Taiwanese patients with MPN. We identified CALR mutations in patients with MPN using the high-resolution melting (HRM) analysis. Additionally, the HRM analysis was compared with ipsogen CALR RGQ PCR. To confirm the results of HRM and ipsogen CALR RGQ PCR, sequencing analysis was also conducted all the samples. RESULTS: Up to 6.25% of CALR mutations were successfully detected in patients with MPN using HRM analysis. Eight out of 65 patients (12.3%) were positive for the presence of CALR mutation, including p.L367fs*46 and p.K385fs*47. The results proved 100% comparable to those obtained using ipsogen CALR RGQ PCR. CONCLUSIONS: The HRM analysis and ipsogen CALR RGQ PCR are feasible and reliable techniques for the detection of CALR mutation. Furthermore, HRM offers several benefits, for example, it is time-saving, inexpensive, and does not require many personnel.

CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism.

B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the effect of CDK9i on B-ALL cells and the underlying mechanisms remain unclear. In this study, we showed that CDK9i induced the apoptosis of B-ALL cells in vitro by activating the apoptotic pathways. In addition, CDK9i restrained the glycolytic metabolism of B-ALL cells, and CDK9i-induced apoptosis was enhanced by co-treatment with glycolysis inhibitors. Furthermore, CDK9i restained the glycolysis of B-ALL cell lines by markedly downregulating the expression of glucose transporter type 1 (GLUT1) and the key rate-limiting enzymes of glycolysis, such as hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Moreover, cell apoptosis was rescued in B-ALL cells with over-expressed c-Myc after treatment with CDK9i, which is involved in the enhancement of glycolytic metabolism. In summary, our findings suggest that CDK9 inhibitors induce the apoptosis of B-ALL cells by inhibiting c-Myc-mediated glycolytic metabolism, thus providing a new strategy for the treatment of B-ALL.

Bromodomains and Extra-Terminal (BET) Inhibitor JQ1 Suppresses Proliferation of Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolysis.

BACKGROUND Acute lymphocytic leukemia (ALL) is a common blood cancer which induces high mortality in children. Bromodomains and extra-terminal (BET) protein inhibitors, such as JQ1 and ARV-825, are promising cancer therapeutic agents that can be used by targeting c-Myc. A recent work reported that JQ1 effectively attenuates ALL in vitro by suppressing cell proliferation and accelerating apoptosis. The purpose of this research was to probe into the potential mechanism of how JQ1 inhibits ALL cell proliferation in vitro. MATERIAL AND METHODS Cell viability of ALL cells were measured by CTG after treatment by JQ1. Cell cycle analysis was done by EdU and PI staining. Cell apoptosis was assessed by Annexin V/PI staining. Glycolysis was detected using Seahorse and LC-MS kits. The expression of glycolytic rate-limiting enzymes was assessed by RNA-seq, qRT-PCR, and Western blot. RESULTS JQ1 suppressed cell proliferation by arresting the cell cycle and inducing the apoptosis of acute lymphocytic leukemia cells. JQ1 inhibited cell proliferation of B-ALL cells by restraining glycolysis. Conversely, the cell cycle block of B-ALL cells induced by JQ1 was partially abolished after pretreatment with 2-Deoxy-D-glucose (2-DG), an inhibitor of glycolysis. Furthermore, JQ1 restrained the glycolysis of B-ALL cell lines by remarkably downregulating the rate-limiting enzymes of glycolysis, such as hexokinase 2, phosphofructokinase, and lactate dehydrogenase A. Moreover, the cell cycle arrest was reversed in B-ALL cells with overexpressed c-Myc treated by JQ1, which is involved in the enhancement of glycolysis. CONCLUSIONS The BET inhibitor JQ1 suppresses the proliferation of ALL by inhibiting c-Myc-mediated glycolysis, thus providing a new strategy for the treatment of ALL.

Steroidal constituents from Helleborus thibetanus and their cytotoxicities.

Thibetanosides E-H (1-4), four new steroidal constituents including three rare sulfonates (2-4), were isolated from the roots and rhizomes of Helleborus thibetanus, together with nine known steroidal compounds (5-13). Their structures were elucidated by detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical evidence. In this study, compounds 2-13 were evaluated for their cytotoxic activities against HCT116, A549 and HepG2 tumor cell lines in vitro. Among them, compound 8 (thibetanoside C) showed cytotoxicities against A549 cells(IC50 39.6 ± 1.9 µmol·L-1) and HepG2 cells(IC50 41.5 ± 1.1 µmol·L-1), respectively. Compound 9 (23S, 24S)-24-[(O-ß-D-fucopyranosyl)oxy]-3ß, 23-dihydroxy-spirosta-5, 25(27)-diene-1ß-ylO-(4-O-acetyl- α-L-rhamnopyranosyl)-(1→2)-O-[ß-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside) showed cytotoxicity against HCT116 cells(IC50 33.6 ± 2.1 µmol·L-1).

Effect of adenovirus-mediated overexpression of PTEN on brain oxidative damage and neuroinflammation in a rat kindling model of epilepsy.

BACKGROUND: Epilepsy is a chronic and severe neurological disorder. Phosphatase and tensin homolog deleted on chromosome ten (PTEN)-deficient mice exhibit learning and memory deficits and spontaneous epilepsy. The aim of this study was to investigate the role of PTEN in brain oxidative damage and neuroinflammation in a rat model of epilepsy. METHODS: An adenovirus (Ad)-PTEN vector was constructed, and status epilepticus (SE) was induced in 41 model rats using lithium chloride-pilocarpine. Thirty-six SE rats were then allocated into the Ad-PTEN, Ad-LacZ, and SE groups, those were administered intracerebroventricular injections of Ad-PTEN, Ad-enhanced green fluorescent protein, and phosphate buffer saline, respectively. The normal group was comprised of healthy Sprague-Dawley rats. Nissl staining was conducted to evaluate neuronal damage, and immunohistochemistry was conducted to observe the morphology of cells in the hippocampal CA1 region and the distribution of ionized calcium-binding adaptor molecule 1 (Iba1) and ED1 (rat homologue of human CD68). Levels of apoptosis-related proteins, inflammatory-related factors, and oxidative stress-related markers (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD], and malondialdehyde [MDA]) were measured. Comparisons between multiple groups were conducted using one-way analysis of variance (ANOVA), and pairwise comparisons after ANOVA were conducted using the Tukey multiple comparisons test. RESULTS: After SE induction, PTEN expression in the rat brain exhibited a four-fold decrease (P = 0.000) and the expression of both Iba1 and ED1 increased. Furthermore, significant neuronal loss, oxidative damage, and neuroinflammation were observed in the SE rat brain. After intracerebroventricular injection of Ad-PTEN, PTEN expression exhibited a three-fold increase (P = 0.003), and the expression of both Iba1 and ED1 decreased. Additionally, neurons were restored and neuronal apoptosis was inhibited. Furthermore, ROS and MDA levels decreased, GSH level and SOD activity increased, and neuroinflammation was reduced. CONCLUSION: Our study demonstrated that brain oxidative damage and neuroinflammation in SE rats were ameliorated by intracerebroventricular injection of Ad-PTEN.

Five new polyhydroxylated furostanol saponins from the rhizomes of Tupistra chinensis.

Five new polyhydroxylated furostanol saponins were isolated from the roots and rhizomes of Tupistra chinensis, and their structures were determined as tupistrosides J-N (1-5), together with four known furostanol saponins (6-9), on the basis of physico-chemical properties and spectral analysis. Among them, compounds 3 and 5 showed cytotoxicity against human cancer cell lines SW620 with IC50 values of 72.5 ± 2.4 and 77.3 ± 2.5 µmol·L-1, respectively. Compound 4 showed cytotoxicity against human cancer cell line HepG2 with IC50 value of 88.6 ± 2.1 µmol·L-1.

Blocking ATM-dependent NF-κB pathway overcomes niche protection and improves chemotherapy response in acute lymphoblastic leukemia.

Bone marrow (BM) niche responds to chemotherapy-induced cytokines secreted from acute lymphoblastic leukemia (ALL) cells and protects the residual cells from chemotherapeutics in vivo. However, the underlying molecular mechanisms for the induction of cytokines by chemotherapy remain unknown. Here, we found that chemotherapeutic drugs (e.g., Ara-C, DNR, 6-MP) induced the expression of niche-protecting cytokines (GDF15, CCL3 and CCL4) in both ALL cell lines and primary cells in vitro. The ATM and NF-κB pathways were activated after chemotherapy treatment, and the pharmacological or genetic inhibition of these pathways significantly reversed the cytokine upregulation. Besides, chemotherapy-induced NF-κB activation was dependent on ATM-TRAF6 signaling, and NF-κB transcription factor p65 directly regulated the cytokines expression. Furthermore, we found that both pharmacological and genetic perturbation of ATM and p65 significantly decreased the residual ALL cells after Ara-C treatment in ALL xenograft mouse models. Together, these results demonstrated that ATM-dependent NF-κB activation mediated the cytokines induction by chemotherapy and ALL resistance to chemotherapeutics. Inhibition of ATM-dependent NF-κB pathway can sensitize ALL to chemotherapeutics, providing a new strategy to eradicate residual chemo-resistant ALL cells.

The potential neuritogenic activity of aqueous extracts from Morchella importuna in rat pheochromocytoma cells.

The aim of this study was to explore the neuritogenic effects of aqueous extracts from the fruiting bodies of Morchella importuna (MEA). 3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was carried out to assess the cytotoxicity of MEA. Neurite outgrowth stimulation assay was used to evaluate the potentiation of neuritogenic activity induced by MEA. The specific inhibitors for TrkA, MEK/ERK and PI3K signaling pathway were served to clarify the mechanism of MEA's neuritogenic effects. It was shown that MEA could mimic neuritogenic activity of NGF, a kind of representative neurotrophic factors with no significant cytotoxicity, and stimulate neurite outgrowth in a dose-dependent manner of PC12 cells. The neuritogenic activity induced by MEA required activity of PI3K/Akt and MEK/ERK1/2 signaling pathways, as well as parts of TrkA receptor. Accordingly, MEA could be used as a promising neuritogenic-stimulation compound for nervous diseases treatment.

Guidelines for treating iron overload in myelodysplastic syndromes: a Taiwan consensus statement.

Iron overload is common in myelodysplastic syndrome (MDS) patients, and an accumulation of evidence shows that iron chelation may have benefits in these patients. However, discussion and consensus about iron chelation therapy (ICT) for MDS patients is lacking in Taiwan and other Southeast Asian countries. An Expert Panel in Taiwan was organized in 2011 to develop iron overload guidelines and provide a uniform reference for physicians treating MDS patients with iron overload, with specific regard to when to initiate ICT, in which patients, and the clinical and scientific rationale behind its use.

[Expression and significance of telomerase activity of lens epithelial cells in posterior capsule opacification of rabbits].

OBJECTIVE: To explore the expression of telomerase activity of the lens epithelial cells in posterior capsule opacification of rabbits. METHODS: Clear corneal tunnel phacoemulsification was performed in both eyes of 11 New Zealand rabbits. After the model of posterior capsule opacification succeed in all eyes. Then, telomerase activity of the lens epithelial cells in the equator and posterior capsule opacification of 20 eyes was detected with TRAP-ELISA and TRAP-PAGE techniques. RESULTS: HepG2 cells were used as positive controls. Telomerase activity was detected in the lens epithelial cells in the equator capsule and posterior capsule opacification in rabbits, which showed several dim gradient stripped electrophoresis pattern. A450 - 690 value of telomerase activity in the equator capsule and posterior capsule opacification was 0.85 +/- 0.23 and 0.67 +/- 0.19, respectively, indicating statistically significant difference (t = 2.526, 0.021; P < 0.05). CONCLUSIONS: Telomerase activity exists in the lens epithelial cells of posterior capsule opacification in rabbits. The telomerase activity in this area is lower than that in the equator capsule.

[Pathological study of unexpected sudden death clustered in family or village in Yunnan province: report of 29 cases of autopsy].

OBJECTIVE: To investigate the pathological features and causes of sudden death clustered in family or village in Yunnan province so as to provide the morphological basis for exploring its etiology and medical intervention. METHODS: Autopsy was performed on 29 cases of clustered in family or village in Yunnan province during the period 1991-2006, 16 males and 13 females, aged 32 (8-69), accounting for 10.2% of whole sudden unexpected deaths occurring in the same period. The heart, lung, liver, spleen, brain, kidney, intestinal tract, and other organs were examined macroscopically and histologically, including a study of cardiac conduction system in 5 cases. Pathological diagnosis of myocarditis was based on the Dallas Criteria and World Heart Federation's consensus while the histological evaluation of Keshan disease referred the China national guideline for pathological diagnosis of Keshan disease. RESULTS: Based on the main pathological changes and the causes of death, these cases were classified into seven groups (group A-G). Group A comprised 11 cases (38%) with lymphocytic myocarditis accompanied with focal myocardial necrosis or degeneration. Group B comprised 3 cases (10%) with neutrophil myocarditis accompanied with focal myocytolysis or coagulation necrosis. Group C comprised 4 cases (14%) with arrhythmogenic right ventricle cardiomyopathy in which fatty infiltration of myocardium was the only pathological finding. Group D comprised 2 cases (7%) with ischemic heart disease in which fresh or old foci of myocardial infarction were found but coronary stenosis was shown only in one case. Group E comprised 2 cases (7%) with left ventricle hypertrophy and obstructive muscle bundle in the outflow of left ventricle. Group F comprised 2 cases (7%) with allergic bronchitis or chronic bronchitis and pulmonary emphysema. Group G comprised the remaining 5 cases (17%) without any pathological finding that could explain sudden death. No cases suffered with Keshan disease and dilated cardiomyopathy. Focal but not diffuse inflammatory infiltration was the prominent histological feature of myocarditis in Yunnan cases. Among the five cases with histological examination of cardiac conduction system, 2 cases were detected to suffer from acute hemorrhage in His bundle and its left branching site, and the atrioventricular node of 1 case was involved. Different pathological changes coexisted in 4 pairs of family members as a cluster of sudden deaths. 3 of 4 first deaths had focal myocarditis and the other one had chronic infection. But 3 secondary deaths had myocardial ischemia and the other one had arrhythmogenic right ventricle cardiomyopathy. Pulmonary edema, acute respiratory infection and congestive or ischemic liver necrosis were found in some cases simultaneously. CONCLUSION: The pathological changes of the cases of clustered sudden death in Yunnan province are various, such as myocarditis, myocardial dysplasia and the other lethal heart-lung disorders. No case of Keshan disease has been found. Arrhythmogenic right ventricle cardiomyopathy and other foundational heart diseases might act as a background. It is very hard to contribute only one etiological factor to the clustering of sudden death in Yunnan. It was most likely that multiple factors cluster and trigger an outbreak of death in a definite time and space.

[Electrocardiogram analysis in high risk population of unexplained sudden death in Yunnan province].

OBJECTIVE: The purpose of this study was to analyze the electrocardiographic features of the people living in the area with high incidence of unexplained sudden deaths in Yunnan province. METHOD: The electrocardiograms of 338 residents from three villages (Dayao, Ninglang, Heqing) with high incidence of unexplained sudden deaths and one control village (Dali) were analyzed [averaged age was (33.4 +/- 11.7) years, 175 men and 163 women]. RESULTS: The incidence of cardiac arrhythmias was similar low in all groups. The left ventricular hypertrophy was observed in 34.6% of residents from Dayao. QTc significantly prolonged in the residents from all 3 high incidence areas compare the control area of Dali [control (386.8 +/- 27.22) ms, Ninglang (428.92 +/- 25.71) ms, Heqing (440.67 +/- 28.03) ms, Dayao (417.7 +/- 24.00) ms, P < 0.05 vs. control]. Incidence of U wave was significantly higher in Heqing village than that in control village (P < 0.05). The QUc of these 3 villages was: (613.67 +/- 37.34) ms, (597.19 +/- 46.47) ms, (608.59 +/- 39.59) ms respectively, and also significantly longer than the control village of Dali (589.33 +/- 41.27) ms (P < 0.05). The typical pattern of U wave presents as enlarged U wave and apparent T-U complex. In the 7 residents who have the family history of unexplained sudden death, 6 residents have U wave, and 4 of them present typical U wave pattern. CONCLUSION: The significant ECG changes in villages with high incidence of unexplained sudden death in Yunnan province were prolonged QTc, enlarged U wave and apparent T-U complex and these ECG features suggested the repolarization abnormalities of the heart in these subjects.