1.Predictive value of T2-FLAIR signal suppression rate for 1p/19q molecular features in lower-grade gliomas
Hanwei WANG ; Linlan ZENG ; Mimi ZHAO ; Xuan LI ; Qisheng RAN ; Jing TIAN ; Jie SUN ; Lizhao CHEN ; Shunan WANG
Journal of Army Medical University 2024;46(18):2121-2129
Objective To evaluate the predictive value of T2-fluid attenuated inversion recovery (FLAIR)signal suppression rate for the short arm of chromosome 1 and long arm of chromosome 19 (1p/19q)molecular features in lower-grade gliomas (LGG),and to construct and verify the predictive model based on magnetic resonance imaging (MRI)tumor features and T2-FLAIR signal suppression rate.Methods Clincal and imaging data of the patients with pathologically confirmed supratentorial LGG (WHO grade 2~3)in our medical center from 2017 to 2021 were collected and retrospectively analyzed.According to the results of postoperative molecular pathology,they were divided into 1 p/19q-codeleted (1 p/19q-Codel)and 1 p/19q-noncodeleted (1 p/19q-Noncodel)groups.MRI tumor features were blindly assessed by 2 neuroradiologists.Five circular regions of interest were respectively delineated in the tumor area and the normal-appearing white matter in contralateral semioval center using the hot-spot method in order to calculate the T2-FLAIR signal suppression rate.The differences of clinical features,MRI tumor features and T2-FLAIR signal suppression rate were analyzed between the 2 groups.Univariate and multivariate logistic regression analyses were used to screen independent predictors and constructa predictive model and nomogram.Receiver operating characteristic (ROC)curve,calibration curve and Hosmer-Lemeshow test were applied to assess the model performance,and the model was internally validated by bootstrap method.Results A total of 146 supratentorial LGG patients were enrolled,including 68 being assigned into the 1 p/19q-Codel group and 78 into the 1 p/19q-Noncodel group.The T2-FLAIR signal suppression rate was 0.43 (0.28,0.62)in the 1 p/19q-Noncodel group,which was significantly higher than that in the 1 p/19q-Codel group[0.29 (0.24,0.35),P<0.001].Multivariate logistic regression analysis showed that T2-FLAIR signal suppression rate>0.374 (P<0.001),cortex infiltration (P=0.001) and calcification (P=0.004) were independent predictors for 1 p/19q status.The AUC value of T2-FLAIR signal suppression rate>0.374 in predicting 1 p/19q-Noncodel was 0.720,the sensitivity was 60.26% and the specificity was 83.82%.DeLong test indicated that T2-FLAIR signal suppression rate>0.374 was more effective than T2-FLAIR mismatch sign in predicting 1 p/19q molecular features (P<0.001).ROC curve analysis suggested that the predictive model established by T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification had good performance,with an AUC value of 0.808,and the AUC value verified internally by bootstrap method was 0.807.At the same time,the calibration and goodness of fit of the model were good.Conclusion T2-FLAIR signal suppression rate can be used as a quantitative imaging marker to predict 1 p/19q-Noncodel LGG.The predictive model with T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification can effectively predict 1 p/19q molecular features.
2.MicroRNA-145 Gene Modification Enhances the Retention of Bone Marrow-Derived Mesenchymal Stem Cells within Corpus Cavernosum by Targeting Krüppel-Like Factor 4
Daoyuan HU ; Yunlong GE ; Yuhang XI ; Jialiang CHEN ; Hua WANG ; Chi ZHANG ; Yubin CUI ; Lizhao HE ; Ying SU ; Jun CHEN ; Cheng HU ; Hengjun XIAO
The World Journal of Men's Health 2024;42(3):638-649
Purpose:
The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated.
Materials and Methods:
The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system.
Results:
In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2′-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253.
Conclusions
Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.
3.Association Between Metabolic Risk Factors and Cognitive Impairment in Schizophrenia Based on Sex
Hongna HUANG ; Lizhao DU ; Zhengping PU ; Yuan SHI ; Zifan XIAO ; Xi CHEN ; Shun YAO ; Lijun WANG ; Zezhi LI ; Ting XUE ; Donghong CUI
Psychiatry Investigation 2023;20(10):930-939
Objective:
Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association.
Methods:
We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia.
Results:
Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients.
Conclusion
Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.
4.Correlation between systemic immune-inflammation index and prognosis in patients with hepatic alveolar echinococcosis
Xiaobin CHEN ; Jiaqi YUAN ; Zhixin WANG ; Haining FAN ; Zhaojun XU ; Xuepeng MEI ; Haijiu WANG ; Jiamin MA ; Ying ZHOU ; Lizhao HOU
Journal of Clinical Hepatology 2021;37(2):375-379
ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P<0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII >758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of >50% and a mean survival time of 55.584 months (95% confidence interval[CI]: 53550-57.617), while the high SII group had a cumulative survival rate of <50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P<005). The univariate analysis showed that SII >758.92 (hazard ratio [HR]=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.
5. Application of continuous iliac fascial interstitial obstruction in the placement of anaesthesia in the vertebral canal of the elderly femoral fractures and postoperative analgesia
Lizhao JIN ; Tijie DING ; Meihua HUANG ; Xianghuan CHEN
Chinese Journal of Primary Medicine and Pharmacy 2018;25(9):1121-1125
Objective:
To investigate the effect of continuous iliac fascia space block on the placement of body position and postoperative analgesia in patients with femoral fractures.
Methods:
60 patients with senile selective unilateral femoral fracture, aged 68-87 years old, weight 49-70kg, ASA grade II-III were selected, and they were randomly divided into iliac fascia block group (A group) and intravenous analgesia group (B group) according to the digital, 30 cases in each group.The two groups underwent lumbar epidural anesthesia, A group received continuous fascia iliaca compartment block 15 min before the the body position.B group was routinely given combination of lumbar and hard anesthesia.After operation, A group was connected with the automatic infusion pump continuous infusion of 0.2% ropivacaine 0.1mL·kg-1·h-1.B group received controlled intravenous analgesia, postoperative given loading dose of dezocine intravenous infusion of 5mg with automatic injection pump for dezocine 0.01mg·kg-1·h-1.When the patients entered the room (T0) and just after the placement of the body position (T1), the heart rate, diastolic blood pressure and systolic blood pressure were measured and recorded.At postoperative 2, 4, 6, 12, 24 and 48h, the VAS scores and pethidine usage during surgery, the adverse reaction were recorded.
Results:
The heart rate, diastolic pressure and systolic pressure at T1 in A group had no significant change compared with T0 (all
6.CD133 epitope vaccine with gp96 as adjuvant elicits an antitumor T cell response against leukemia.
Shuo WANG ; Hongxia FAN ; Yang LI ; Huaguo ZHENG ; Xin LI ; Changfei LI ; Lizhao CHEN ; Ying JU ; Songdong MENG
Chinese Journal of Biotechnology 2017;33(6):1006-1017
Cancer stem cells are currently under intensive investigation due to their capabilities for tumor initiation, self-renewal, and resistance to chemotherapy. CD133 is implicated in stemness and the malignancy of tumor cells. Here, we explored heat shock protein gp96 adjuvanted CD133 epitope vaccine against leukemia. We screened and identified three H2-Kd-restricted cytotoxic T lymphocyte (CTL) epitopes derived from CD133, CD133₄₁₉₋₄₂₈, CD133₇₀₂₋₇₁₀ and CD133₇₆₀₋₇₆₉. The immunogenicity and antitumor activity of the epitope vaccine using heat shock protein gp96 as adjuvant were further determined in CD133⁺ leukemia xenograft mice. Finally, we demonstrate that adoptive transfer of epitope-specific CTLs led to suppression of leukemia growth. Our data therefore provide the basis for designing a CD133 epitope vaccine to activate specific CTLs against CD133⁺ leukemia and other cancers.
7.Pharmacokinetics characterization and toxicology of PNIPAAm-PEO nanoparticles loaded norvancomycin in rabbit eyes
Lizhao, WANG ; Xiang, CHEN ; Yusheng, WANG ; Xiaonong, CHEN ; Qingwei, WANG
Chinese Journal of Experimental Ophthalmology 2014;32(3):200-205
Background The penetration of bacterial agents into the vitreous cavity is difficult because of the existence of blood-retina barrier.So conventional drug therapy is not enough effective on endophthalmitis.Drug delivery systems can decrease drug dose and reduce the drug toxicity.To construct nano controlled-release system of anti-bacterial agents is very important for the treatment of intraocular infectious diseases.Objective This study was to investigate the toxicology and intraocular pharmacoklnetics of intravitreal PNIPAAm-PEO loaded norvancomycin nanoparticles (NV-PNIPAAm-PEO) in normal rabbit eyes.Methods NV-PNIPAAm-PEO was constructed with the drug-loading rate about 22%,and then the drug gelatin solution (20 g/L) was prepared using normal saline solution.Forty-one New Zealand albino rabbits were randomized divided into experimental group and control group.20 g/L drug gelatin solution 0.1 ml was monocularly injected into the vitreous cavity in the experimental group,and the equal volume of sterilized normal saline solution was used in the control group.In 1 day,2,3,7,14,21 and 28 days after injection,ocular anterior and posterior segments were examined by slit lamp microscope and Bsonography,and electroretinogram (ERG) was recorded and the histopathological examination was performed to evaluate the biotoxicity of the drug.Norvancomycin contents in the cornea homogenate,aqueous humor,vitreous,retinochoroid homogenate were detected by high performance liquid chromatography (HPLC) system.Results The anterior and posterior segments were normal by the slit lamp microscope and B-sonography 1-28 days after injection of NV-PNIPAAm-PEO.In 7,14,21 and 28 days after injection,there were no statistically significant difference in the a-wave latency and amplitude of max-ERG between the two groups,as well as the b-wave amplitude(P>0.05).The histopathological examination showed that the retinal structure was normal in both groups.HPLC assay showed that the norvancomycin level was gradually declined in different eye tissues from 1 day through 28 days after injection.Norvancomycin was undetectable in the cornea during the observing duration.The maximal norvancomycin content in the blood plasma was (0.34 ± 0.11) mg/L in the second day,and norvancomycin content ranged (0.08 ± 0.04)-(2.16±0.07) mg/L in the aqueous humor,(0.11 ±0.22)-(2.54 ±0.38) μg/g in the chorioretina,respectively.The drug concentration was (5.65 ± 1.14)-(406.69 ± 21.05) mg/L in the vitreous,which was higher than the minimal inhibitory concentration (MIC) to the most gram-positive bacteria.Conclusions The intravitreal injection of 22% NV-PNIPAAm-PEO maintains the therapeutic drug concentration till 21 days in vitreous without the toxic effect on eye tissues,suggesting a great treating potential for intraocular infecting diseases.
8.Protein kinase A signal pathway regulating corticotropin-releasing hormone mRNA expression in hypothalamic slice of rats in vitro
Lizhao CHEN ; Minhui XU ; Jihon ZHOU
Journal of Third Military Medical University 2003;0(10):-
Objective To investigate protein kinase A (PKA) signal regulatory mechanism of corticotropin-releasing hormone (CRH) mRNA expression, after CRH stimulated neuron of hypothalamic slices in rats in vitro. Methods After CRH stimulated corticotropin-releasing hormone type 1 receptor (CRH1R) of hypothalamic slices in rats in vitro, the changes of activity of PKA signal pathway and their relationship with CRH mRNA expression were observed by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting. Results CRH may cause the remarkable increase in phosphorylated PKA (P-PKA), phosphorylated cyclic adenosine monophosphate response element-binding protein (P-CREB) and CRH mRNA content in hypothalamic slices in rats. However, CP-l54526 or H89 could have significant inhibition effects on the synthesis of P-PKA, P-CREB and CRH. Conclusion PKA signal pathway in ultrashort positive feedback control of CRH secretion in hypothalamus in the stress due to severe traumas.
9.Endovascular therapy for intracranial vertibrobasil dissectimng aneurysm
Journal of Third Military Medical University 2003;0(15):-
Objective To summarize the radiographic characteristic and endovascular interventional technique in patients with intracranial vertibrobasil dissectimng aneurysm.Methods Totally 30 patients of intracranial vertibrobasil dissectimng aneurysm were embolized by endovascular therapy,4 with stent implantation technique,26 with stent assisted coiling technique.Results Patency of parent artery was restored in 25 cases(83.3%),and except 1 case(3.3%) of postoperative intracerebral hemorrhage,no other complications occurred.All patients were followed up from 5 months to 34 months(average 11.2).All cases recovered well.No case died in the cohort.Conclusion Intracranial vertibrobasil dissectimng aneurysm has following angiographic features: string sign,pearl and string sign,and double lumen sign.Therapeutic strategies depend on clinical symptoms,the location,configuration of the dissection,and the relationship of vital branches around.The results suggested that embolization of intracranial vertibrobasil dissectimng aneurysm with coils is minimally invasive,safe,effective and reliable.
10.Treatment of idiopathic trigeminal neuralgia with gamma knife: a report of 87 cases
Lizhao CHEN ; Minhui XU ; Yongwen ZOU ; Guangxin CHEN ;
Journal of Third Military Medical University 2003;0(16):-
Objective To evaluate the therapeutic efficacy of gamma knife for the treatment of idiopathic trigeminal neuralgia Methods An analysis of 87 cases with idiopathic trigeminal neuralgia treated by gamma knife in our department in the past 5 years was performed In all cases, 4 mm isocenter was targeted at the proximal nerve at the root entry zone located by MRI The target dose varied from 70-90 Gy Results After a follow up of 6-67 months, complete relief of pain occurred in 66 patients (75 9%), 50%-90% relief in 18(20 7%), relief less than 50% in 2(2 3%) but no relief in 1(1 1%) Repeated radiosurgery was performed in 2 patients (2 3%) with recurrent pain After the second radiosurgical procedure, complete relief of pain was found in the 2 patients Two patients(2 3%) experienced facial numbness after radiosurgical procedure Conclusion Gamma knife radiosurgery is a minimally invasive technique for the treatment of trigeminal neuralgia with few complications Repeated radiosurgical procedure may result in relief of pain, but the long term outcome of gamma knife surgery for trigeminal neuralgia needs to be further studied

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