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1.
Int J Biol Sci ; 20(7): 2640-2657, 2024.
Article En | MEDLINE | ID: mdl-38725843

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.


Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , HMGA1a Protein , MTOR Inhibitors , Proto-Oncogene Protein c-ets-1 , Humans , Cell Line, Tumor , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/genetics , Proto-Oncogene Protein c-ets-1/metabolism , Proto-Oncogene Protein c-ets-1/genetics , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , HMGA1a Protein/metabolism , HMGA1a Protein/genetics , MTOR Inhibitors/pharmacology , MTOR Inhibitors/therapeutic use , Tacrolimus Binding Protein 1A/metabolism , Tacrolimus Binding Protein 1A/genetics , Animals , Sirolimus/pharmacology , Sirolimus/therapeutic use , Signal Transduction/drug effects , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/drug therapy , TOR Serine-Threonine Kinases/metabolism , Mice , Mice, Nude
2.
Mol Psychiatry ; 2024 Jan 25.
Article En | MEDLINE | ID: mdl-38273109

Microbial infection as a type of environmental risk factors is considered to be associated with long-term increased risk of dementia, including Alzheimer's disease (AD). AD is characterized by two neuropathologically molecular hallmarks of hyperphosphorylated tau and amyloid-ß (Aß), the latter generated by several biochemically reactive enzymes, including γ-secretase. However, how infectious risk factors contribute to pathological development of the AD core molecules remains to be addressed. In this work, we utilized a modified herpes simplex virus type 1 (mHSV-1) and found that its hippocampal infection locally promotes Aß pathology in 5 × FAD mice, the commonly used amyloid model. Mechanistically, we identified HSV-1 membrane glycoprotein US7 (Envelope gI) that interacts with and modulates γ-secretase and consequently facilitates Aß production. Furthermore, we presented evidence that adenovirus-associated virus-mediated locally hippocampal overexpression of the US7 aggravates Aß pathology in 5 × FAD mice. Collectively, these findings identify a herpesviral factor regulating γ-secretase in the development and progression of AD and represent a causal molecular link between infectious pathogens and neurodegeneration.

3.
J Med Virol ; 96(1): e29357, 2024 01.
Article En | MEDLINE | ID: mdl-38235532

The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global threat, exacerbated by the emergence of viral variants. Two variants of SARS-CoV-2, Omicron BA.2.75 and BA.5, led to global infection peaks between May 2022 and May 2023, yet their precise characteristics in pathogenesis are not well understood. In this study, we compared these two Omicron sublineages with the previously dominant Delta variant using a human angiotensin-converting enzyme 2 knock-in mouse model. As expected, Delta exhibited higher viral replication in the lung and brain than both Omicron sublineages which induced less severe lung damage and immune activation. In contrast, the Omicron variants especially BA.5.2 showed a propensity for cellular proliferation and developmental pathways. Both Delta and BA.5.2 variants, but not BA.2.75, led to decreased pulmonary lymphocytes, indicating differential adaptive immune response. Neuroinvasiveness was shared with all strains, accompanied by vascular abnormalities, synaptic injury, and loss of astrocytes. However, Immunostaining assays and transcriptomic analysis showed that BA.5.2 displayed stronger immune suppression and neurodegeneration, while BA.2.75 exhibited more similar characteristics to Delta in the cortex. Such differentially infectious features could be partially attributed to the weakened interaction between Omicron Spike protein and host proteomes decoded via co-immunoprecipitation followed by mass spectrometry in neuronal cells. Our present study supports attenuated replication and pathogenicity of Omicron variants but also highlights their newly infectious characteristics in the lung and brain, especially with BA.5.2 demonstrating enhanced immune evasion and neural damage that could exacerbate neurological sequelae.


COVID-19 , Communicable Diseases , Nervous System Diseases , Animals , Mice , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
4.
Gut Microbes ; 15(2): 2293312, 2023 Dec.
Article En | MEDLINE | ID: mdl-38087436

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.


Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Metformin , Humans , Mice , Animals , Intestines , Verrucomicrobia/metabolism
5.
Exp Neurol ; 365: 114418, 2023 07.
Article En | MEDLINE | ID: mdl-37085003

Subarachnoid hemorrhage (SAH) is a severe acute cerebrovascular event that not only impairs the central nervous system but also negatively affects various other organs, including the heart. The underlying mechanisms, however, remain unclear. In this study, we discovered that mice with SAH exhibited significant cardiac injuries, such as extended QT and QTc intervals, cardiac fibrosis, and reduced cardiac ejection fractions. This phenomenon was accompanied by increased galectin-3 expression in the cardiac ventricle and can be reversed by galectin-3 inhibitor TD139. Interestingly, we also observed increased co-expression of galectin-3 in macrophage within the heart tissue of SAH mice. Additionally, when macrophage activation was suppressed using the beta-blocker propranolol, cardiac function improved, and galectin-3 expression in the cardiac tissue decreased. Collectively, our findings offer new insights into the role of galectin-3 in SAH-related cardiac dysfunction and suggest a macrophage-galectin-3 axis as a potential therapeutic strategy.


Heart Diseases , Subarachnoid Hemorrhage , Animals , Mice , Galectin 3/genetics , Galectin 3/metabolism , Subarachnoid Hemorrhage/metabolism , Heart , Macrophages/metabolism , Heart Diseases/complications
6.
Ther Adv Chronic Dis ; 14: 20406223231160688, 2023.
Article En | MEDLINE | ID: mdl-36969501

Background: Systemic lupus erythematosus-associated immune thrombocytopenia (SLE-ITP) is characterized by relapse. The risk factors of relapse and appropriate maintenance therapy strategy deserve further exploration. Objectives: To determine the risk factors for relapse and appropriate maintenance therapy in significant SLE-ITP patients (a platelet count ⩽30 × 109/l) after the first complete response. Design: Retrospective cohort study using the medical records of 105 patients diagnosed as significant SLE-ITP in Fujian Medical University Union Hospital during December 2012 to March 2021. Patients were followed through a call for observations in January 2022. Methods: Data including demographics, initial clinical feature, induction and maintenance therapy, and outcome at the end of follow-up were analyzed. Risk factors for significant relapse were analyzed using multivariate logistic regression models. The cumulative hazard of significant relapse and the duration of response were estimated, and the differences in outcome between groups were compared using the Cox regression analysis. Results: A total of 65 significant SLE-ITP patients were eligible for the final analysis. Median [interquartile range (IQR)] follow-up duration and median [IQR] duration of response were 62.2 [41.0-79.6] months and 43.4 [20.3-68.7] months, respectively. After the first complete response, 19/65 (29.2%) had a significant relapse. Compared with sustained clinical remission (SCR) + sustained response (SR) group, significant relapse group had a higher proportion of discontinued patients (47.4% versus 8.7%, p = 0.001). Among the 13 discontinued patients, the duration of maintenance therapy of the patients in significant relapse group was significantly shorter than that of the patients in SCR + SR group (months, median [IQR], 43.1 [32.0-62.4] versus 12.0 [5.1-22.0], p = 0.009). Multivariate logistic regression analysis showed that drug withdrawal was an independent risk factor for significant relapse [odds ratio (OR) = 10.4, confidence interval (CI) 95% 2.2-47.8, p = 0.003]. There was no significant difference between glucocorticoids (GCs) + hydroxychloroquine (HCQ) group and GCs + HCQ + immunosuppressive agents (ISAs) group in significant relapse rate (26.7% versus 22.2%, p > 0.05). The two SR curves of GCs + HCQ and GCs + HCQ+ ISA group basically coincided by the Cox regression analysis, demonstrating comparable long-term outcomes (p > 0.05). Conclusion: Drug withdrawal, especially abrupt withdrawal with insufficient duration of maintenance therapy, is an independent risk factor for significant relapse of SLE-ITP. HCQ combined with GCs is expected to be the first choice of the maintenance therapy for SLE-ITP patients.

7.
Biotechnol Prog ; 39(3): e3328, 2023.
Article En | MEDLINE | ID: mdl-36700726

Oxidative damage has been implicated in the pathogenesis of numerous disorders by affecting the normal functions of several tissues. Further, oxidative stress acts within cells to influence cell morphology and the behavior of cell migration. The movement and migration of cells are crucial during the development of organisms as they transition from embryo to adult, and for the homeostasis of adult tissues. Epicatechin (EC) is a natural flavonoid derived mostly from tea, chocolate, and red wine. We investigated the protective impact of EC on D-galactose(D-gal)/rotenone-injured NIH3T3 cells and found alterations in cell dynamics throughout the procedure. The results reveal that D-gal/rotenone stimulation can cause the cell area to expand and the number of cellular protrusions to increase. EC intervention can considerably minimize the oxidative damage of rotenone on NIH3T3 cells (p < 0.05) but showed little influence on cell damage induced by D-gal. Furthermore, the corrective ability of EC as an antioxidant is reflected in a dose-dependent effect on cell movement, including variations in movement speed and distance. Overall, from the perspective of cell morphology and cell motility, EC has a good protective impact on cells harmed by rotenone induced oxidative damage, as well as corrective properties as an antioxidant to balance intracellular oxidative stress, which allowing for a more comprehensive evaluation of antioxidant performance of EC.


Antioxidants , Catechin , Animals , Mice , Antioxidants/pharmacology , Catechin/pharmacology , NIH 3T3 Cells , Oxidative Stress/drug effects , Rotenone/pharmacology , Galactose/pharmacology , Cell Shape/drug effects , Cell Surface Extensions/drug effects , Protective Agents/pharmacology
8.
Article Zh | WPRIM | ID: wpr-971419

Objective: To introduce a classification of alar retraction, and to discuss the therapeutic strategy of alar retraction with cartilage graft and the satisfaction evaluation of patients after operation. Methods: A retrospective analysis was performed on 88 patients with alar retraction admitted to the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University from January 2015 to December 2020, including 20 males and 68 females, aged 20 to 48 years, with an average age of 28.98 years. All patients underwent external rhinoplasty according to a series of treatment plans determined by the classification of alar retraction based on nostril exposure. Visual Analogue Scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE) were used to conduct satisfaction survey before and 12 months after operation. Wilcoxon signed-rank test was used to analyze patient satisfaction. Results: A total of 88 patients were included in this study. According to the classification of alar retraction based on nostril exposure, 45 cases were mild, 23 cases were moderate, and 20 cases were severe. There were 16 cases of unilateral and 72 cases of bilateral alar retraction. The patients were followed up for 12 to 18 months, with an average of 13.37 months. The VAS score and ROE score after each type of surgery were higher than those before surgery, with statistically significant (all P<0.05). Among them, the difference in VAS score (6.75±1.29) and in ROE satisfaction (67.70±7.38) of patients with severe alar retraction were the most significant improvement. Conclusion: The classification of alar retraction based on nostril exposure in the frontal view can comprehensively evaluate the severity of alar retraction, and makes the treatment algorithms systematic and comprehensive. The satisfaction of patients is relatively high.


Male , Female , Humans , Adult , Rhinoplasty , Retrospective Studies , Patient Satisfaction , Treatment Outcome , Esthetics , Nose/surgery
9.
Acta Pharmaceutica Sinica B ; (6): 2683-2694, 2022.
Article En | WPRIM | ID: wpr-939934

Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.

10.
J Orthop Surg Res ; 16(1): 595, 2021 Oct 14.
Article En | MEDLINE | ID: mdl-34649564

BACKGROUND: Osteoarthritis (OA) is characterized by joint pain and joint function limitation. Hsa_circ_0045714 (circ_0045714) is a novel OA-related circular RNA. However, its repertoire remains to be further clarified in joint chondrocytes. METHODS: RNA and protein expression levels and inflammatory factor levels were detected by real-time quantitative polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. Cell proliferation and apoptosis were determined by colony formation assay, cell counting kit-8 assay and apoptosis assay. Direct interaction was predicted by bioinformatics method and confirmed by dual-luciferase reporter assay. RESULTS: Expression of circ_0045714 and phosphoinositide-3-kinase (PI3K) regulatory subunit 3 (PIK3R3) was declined, and microRNA (miR)-331-3p was promoted in knee articular cartilages and cells from OA patients, as well as interleukin (IL)-1ß-challenged human articular chondrocytes (HAC) cell line. In stimulation of IL-1ß, HAC cells showed a loss of colony formation ability, cell viability and expression of Bcl-2 and Collagen II, allied with an increase in apoptosis rate and levels of IL-6, IL-8 and tumor necrosis factor-α, Bcl-2-associated X protein, cleaved caspase-3, and ADAM with thrombospondin motif-5. Noticeably, overexpressing circ_0045714 and inhibiting miR-331-3p could suppress IL-1ß-evoked these effects, and both were through up-regulating PIK3R3, a key gene in PI3K/AKT signaling pathway. Mechanically, circ_0045714 functioned as competing endogenous RNA (ceRNA) for miR-331-3p and further regulated expression of the downstream target gene PIK3R3. CONCLUSION: There was a novel circ_0045714/miR-331-3p/PIK3R3 ceRNA axis in HAC, and its inhibition might be one mechanism of HAC injury in OA.


MicroRNAs , Osteoarthritis , Chondrocytes , Humans , MicroRNAs/genetics , Osteoarthritis/genetics , Phosphatidylinositol 3-Kinases , RNA, Circular
11.
Article Zh | WPRIM | ID: wpr-798822

Objective@#To investigate the clinical effect of diced cartilage in correcting nasal alar base depression after cleft lip surgery.@*Methods@#A retrospective study was conducted in 15 patients of nasal deformity after lip surgery from January 2018 to January 2019. All the patients were taken from autologous costal cartilage to reconstruct the outline of nasal malformation, and the remaining autologous costal cartilage was cut into 0.5-1.0 mm pieces and filled into the basilar lacunar space of the nasal alar by the 1 ml syringe whose anterior needle nipples was removed. The effects of visual images before and after operation were compared and analyzed by Adobe Photoshop CS6 software. The patients were followed up for 6-15 months (mean 10months). The satisfaction and complications of the patients were investigated.@*Results@#The nasal alar base was significantly elevated and the outline of the nasal deformity was improved in 15 patients after operation. The overall effect was satisfactory and no obvious complications were found. No obvious absorption was found in the follow-up.@*Conclusions@#The application of diced cartilage to correct the nasal alar base depression after cleft lip surgery was a feasible method with important clinical value. It advanced in taking good use of the remaining cartilage and reducing the damage to both the donor and recipient area.

12.
Article Zh | WPRIM | ID: wpr-805722

Objective@#To study the tissue size, calcification characteristics and the correlation between calcification and age and lateral side of 6, 7 and 8 costal cartilage in women, so as to provide reference for clinical application.@*Methods@#From the radiology storage center of Second Xiangya Hospital, 70 cases of female costal cartilage were treated with dual-source CT three-dimensional reconstruction. The reconstructed images were treated with maximum intensity projection (MIP) and volume reconstruction (VR). The length, width and thickness of bilateral 6, 7 and 8 costal cartilage were measured by VR images, and the correlation between calcification rate, calcification degree, calcification type, calcification location, calcification with age and side was observed and analyzed on VR and MIP images. The data were analyzed by SPSS 20.0 and compared by corresponding statistical method, including independent sample t test, chi-square test, logistic regression analysis and variance analysis.@*Results@#(1) The length of costal cartilage on the left was (98.7 ±12.7) mm, (132.8 ±13.8) mm, (81.5 ±11.6) mm, width (12.6 ±1.5) mm, (11.0 ±1.4) mm, (7.4 ±1.1) mm, thickness (8.1 ±0.5) mm, (7.7 ±0.6) mm, (6.6 ±0.6) mm. On the right side, the length of costal cartilage was (95.8 ±11.3) mm, (133.1 ±12.0) mm, (81.7 ±12.3) mm, width (12.2 ±1.4) mm, (11.11 ±1.5) mm, (7.4 ±1.1) mm, thickness (8.2 ±0.6) mm, (7.7 ±0.5) mm, (6.5 ±0.6) mm. There was no significant difference in the length, width and thickness of the left and right sides of the costal cartilage in the same sequence (P>0.05). There were significant differences in length, width and thickness between unilateral costal cartilage with different ordinal numbers (P<0.01). (2) The total calcification rates of left and right costal cartilage were 61.9% (130/210) and 60.0% (126/210), respectively, and there was no significant difference between the two groups (The chi-square was equal to 0.160. The P value was equal to 0.689), but there was no significant difference in left and right total calcification types, total calcification location and total calcification count (P>0.05). There was no significant difference in the total calcification type between left and right, the total calcification location and the total calcification degree count (P>0.05). There was also no significant difference between the two groups (P>0.05). There was no significant difference in the calcification rate between the left and right sides of the 6th, 7th and 8th costal cartilage, but there was significant difference in the total calcification types of the 6th, 7th and 8th costal cartilage (The chi-square was equal to 61.541, P value was less than 0.001). (3)The relationship between calcification rate and age was analyzed by univariate analysis and logistic regression equation. The higher the age, the higher the calcification rate. The relationship between the calcification degree and age of the 6th, 7th and 8th costal cartilage was tested by variance test, and the regression equation showed that the calcification degree of the 6th, 7th and 8th costal cartilage was higher with the age.@*Conclusions@#Preoperative three-dimensional reconstruction and image post-processing of costal cartilage with dual-source CT can accurately measure the amount of cartilage tissue and define the characteristics of calcification, so as to guide the clinical selection of costal cartilage that meets the requirements of operative method. In female patients of different ages undergoing rhinoplasty and external ear reconstruction, the calcification rate of costal cartilage increased with age, but there was no positive correlation. With the increase of calcification with age, artificial materials can be used for cases with severe calcification to avoid the blindness of surgery.

13.
Article Zh | WPRIM | ID: wpr-712367

Objective To introduce the experience of using costal cartilage in oriental secondary rhinoplasty.Methods From January 2012 to December 2016,we used costal cartilage grafts to obtain a functional and aesthetic reconstruction,in which silicone was used in 34 previous cases and e-PTFE was used in 5 cases.Results The mean duration of follow-up was 1.5 years,43 (86%) patients showed high satisfaction with the shape of nose.1 case of infection and 2 cases of costal cartilage warping occurred.1 case was somewhat dissatisfactied with outcome.There was no case of chest wall deformity and pneumothorax,but scar on the chest wall at the donor site was observed in 2 cases.Conclusions We have obtained good aesthetic results using costal cartilage grafts which could display sufficient and stable support for the scaffold of nose.We can conclude that costal cartilage is a good material in secondary rhinoplasty,and can be used to reconstruct an aesthetic nose.

14.
Article Zh | WPRIM | ID: wpr-735093

Objective To discuss the prevention and treatment of the complications of rib rhinoplasty in Chinese.Methods A total of 209 patients received rib rhinoplasty in which postoperative complications happened in 14 cases from Jan.2010 to Aug.2017,and the clinical data were analyzed retrospectively.Results 195 patients showed satisfactory results and no complications.Postoperative complications occurred in 14 cases.There were 12 cases of rib cartilage warping (incidence rate was 5.7%).4 cases were thought that warping was within acceptable range,and 8 cases had satisfactory results after the secondary repair surgery.There were 3 cases of resorption of rib cartilage (incidence rate was 1.4%),of which 2 cases were complicated with cartilage warping and 1 case complicated with infection.None of them underwent repair surgery.The infection complicated with cartilage resorption was 1 case (0.5%).The infection was improved by conservative treatment and the cartilage was not removed.There was 1 case of hypertropic scar on chest wall (incidence rate was 0.5%).Conclusions The warping of cartilage can be significantly reduced by selecting straight section of costal cartilage,preserving the central costal cartilage grafts,symmetrically carving and crosscutting.Meanwhile,sterility and accurate operation can decrease the incidence of infection,aerothorax and scars.

15.
Article Zh | WPRIM | ID: wpr-687423

In order to optimize the prescription and preparation process of norcantharidin/tetrandrine dual loaded liposomes, the dual drug loaded liposomes were prepared by film dispersion-ultrasonic method using norcantharidin-mesoporous silica nanoparticles(MSN-NCTD)and tetrandrine(Tet). With particle size and encapsulation efficiency as comprehensive indexes, the influences of phospholipid cholesterol amount, ultrasonic time and ultrasonic power on prescription process were investigated by orthogonal test; the release characteristics of liposomes were investigated by dialysis method. The results indicated that the best prescription process of prepared norcantharidin/tetrandrine dual loaded liposomes was as follows: phospholipid-cholesterol ratio 2.5:1, ultrasonic time 4 min, ultrasonic power 40%; the encapsulation efficiency was 86.62% and 79.19%respectively for NCTD and Tet;liposomes were well-shaped under the transmission microscope, with average particle size of (207.5±3.6) nm, Zeta potential of (1.345±0.173) mV; and the 48 h cumulative release rates of NCTD and Tet were 85.14% and 85.00% respectively. The experiment results proved that the dual drug loaded liposomes prepared by film dispersion-ultrasonic method had uniform particle size, high encapsulation efficiency and sustained release characteristics.

16.
Article Zh | WPRIM | ID: wpr-807498

Objective@#To investigate the treatment and clinical effect of thin anterolateral thigh perforator flap with sensory nerve in the repair of soft tissue defect of dorsal foot.@*Methods@#During January 2012 to February 2017, 14 cases of soft tissue defect of dorsalis pedis were treated. The flap was designed according to the three-dimensional structure of the defect in the recipient area, and the lateral femoral cutaneous nerve was carried. Free transplantation was performed for repair of soft tissue defect of dorsal foot after fine thinning under microscope. The selected size of the flap ranged from 6 cm×4 cm to 15 cm×9 cm, 10 cases of donor site width is less than or equal to 8 cm with direct suture, 4 cases of donor site wound greater than 8 cm, Free skin graft on the wound surface.@*Results@#After operation, all flaps survived. Meanwhile, superficial necrosis occurred in the distal part of the flap in 1 case due to local infection, and healed after dressing change. All patients were followed up for 6-24 months, the appearance of the flap was pleasant, the texture, color and elasticity of the flap were satisfactory. In addition, Partial skin flap two-point discrimination was 6-10 mm with S2, S3 sensory recovery. During the follow-up, patients were able to walk with normal shoes, no ulcer occurred in the flap, and healed well in donor site.@*Conclusions@#The application of thin anterolateral thigh perforator flap with sensory nerve is safe and reliable in the repair of soft tissue defect of dorsal foot. After the repair, the skin flap has a good appearance and can restore part of the sensation.

17.
Article Zh | WPRIM | ID: wpr-808001

Objective@#To explore flap thinning based on the study of the arterial structure and blood perfusion of the deep inferior epigastric artery perforator (DIEP) flap using computed tomography (CT) angiography.@*Methods@#Clinical imaging study: Preoperative CT angiography was performed in 15 patients with DIEP flap reconstruction to investigate the vascular structure of arterial perforator. Cadaveric imaging study: 10 abdominal specimens harvested from fresh cadavers were cannulated with trocar and injected with contrast medium in the deep inferior epigastric artery perforator. During the perfusion of the contrast medium in the flap, the flap was scanned by three-dimensional CT. The CT data was then sent to CT workstation and the images were processed and reformatted to study the vascular structure of arterial perforators and the blood perfusion.@*Results@#75 artery perforators in clinical study and 40 artery perforators in cadaveric study were chosen and analyzed. The major deep inferior epigastric artery perforators run directly across the deep layer of adipose tissue without bifurcating beneath the Scarpa′s fascia. Above the Scarpa′s fascia, the artery perforators bifurcate and ultimately terminate in the subdermal vascular plexus. Blood perfusion mode: The subdermal vascular plexus served as the only pathway for blood perfusion between perforasomes. There are two different pathways for blood perfusion in the perforasome: the subdermal plexus and the existing vascular structure of perforator.@*Conclusions@#Based on the vascular structure of arterial perforator and blood perfusion of the DIEP flap, thinning of the DIEP flap under the Scarpa′s fascia is safe while thinning above the Scarpa′s fascia should performed according to the blood supply zone of the DIEP flap.

18.
J Neurol Surg A Cent Eur Neurosurg ; 77(4): 321-5, 2016 Jul.
Article En | MEDLINE | ID: mdl-25798798

Background Hemifacial spasm (HFS) is generally treated by microvascular decompression (MVD). Inadequate separation of vessel and nerve or adhesive inflammation surrounding the nerve root may cause recurrence. Objective To explore a method to reduce the incidence of adhesions and to ensure sufficient separation of the offending vessel and nerve during MVD. Methods Fifty-one patients diagnosed with HFS were studied. During the MVD procedure, Teflon sponges were placed between the offending vessels and medulla oblongata to push compressing vessels away from the facial nerve without contacting the nerve. Results Our method of placement of the Teflon sponge effectively shifts the compressing artery and ensures that both the Teflon sponge and offending vessels do not contact the root exit zone. This method also ensures that the Teflon sponge is fixed in place. Conclusion The technique described for the treatment of HFS provides an effective, safe, and durable resolution to patient symptoms that minimizes surgical complications and may be useful in treating HFS.


Hemifacial Spasm/surgery , Microvascular Decompression Surgery/methods , Surgical Sponges , Tissue Adhesions/prevention & control , Adult , Aged , Female , Humans , Male , Microvascular Decompression Surgery/adverse effects , Middle Aged , Polytetrafluoroethylene , Tissue Adhesions/etiology , Treatment Outcome , Young Adult
19.
Article En | WPRIM | ID: wpr-285231

Evidence suggested that glycogen synthase kinase-3β (GSK-3β) is involved in Nogo-66 inhibiting axonal regeneration in vitro, but its effect in vivo was poorly understood. We showed that stereotactic injection of shRNA GSK-3β-adeno associated virus (GSK-3β-AAV) diminished syringomyelia and promoted axonal regeneration after spinal cord injury (SCI), using stereotactic injection of shRNA GSK-3β-AAV (tested with Western blotting and RT-PCR) into the sensorimotor cortex of rats with SCI and by the detection of biotin dextran amine (BDA)-labeled axonal regeneration. We also determined the right position to inject into the sensorimotor cortex. Our findings consolidate the hypothesis that downregulation of GSK-3β promotes axonal regeneration after SCI.


Animals , Humans , Rats , Axons , Metabolism , Dependovirus , Genetics , Glycogen Synthase Kinase 3 beta , Genetics , Metabolism , Nerve Regeneration , Genetics , RNA, Small Interfering , Genetics , Sensorimotor Cortex , Pathology , Spinal Cord Injuries , Genetics , Pathology , Therapeutics , Syringomyelia , Genetics , Pathology , Therapeutics
20.
Article Zh | WPRIM | ID: wpr-815259

OBJECTIVE@#To investigate the association between angiopoietin-like 4 (ANGPTL4) and aldolase A (ALDOA) in human melanoma cell. 
@*METHODS@#Overexpression or knockdown of ANGPTL4 was performed in WM-115 or WM-266-4 cells, respectively. The expression of ANGPTL4 and ALDOA was measured by RT-PCR and Western blot, respectively. The promoter activity of ALDOA gene was determined by luciferase assay.
@*RESULTS@#The promoter activity of ALDOA gene and the expression of ALDOA (mRNA and protein) were increased or decreased in the melanoma cells with overexpression or knockdown of ANGPTL4, which was blocked by selective protein kinase C (PKC) inhibitor or restored by PKC agonist, respectively.
@*CONCLUSION@#ANGPTL4 promotes ALDOA expression in human melanoma cell in a PKC dependent manner.


Humans , Angiopoietin-Like Protein 4 , Angiopoietins , Genetics , Metabolism , Blotting, Western , Cell Line, Tumor , Fructose-Bisphosphate Aldolase , Metabolism , Gene Knockdown Techniques , Melanoma , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism
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