1.Application of virtual reality technology in the foot fracture-assisted surgery
Manman HAN ; Quanwei CUI ; Yong TENG ; Wenju ZHANG
Chinese Journal of Tissue Engineering Research 2017;21(3):378-382
BACKGROUND:The application of virtual reality technology in preoperative simulation can reduce the risk in operation effectively and improve the quality of surgery. Virtual reality technology has very important practical significance in the application of surgery. OBJECTIVE:The reverse engineering and virtual reality technology were used to achieve the preoperative simulation of a case of Pilon fracture. METHODS:The affected bones were reconstructed according to the CT data using the patient’s ankle portion in MIMICS software, and the separated bone fractures were restored. According to the characteristics of virtual reality technology, further processing on bone model was carried out using Geomagic software;the models of the fractured bones were exported with STL format. The restored bone fragments were checked up to determine integrity in the virtual reality operation platform. These models were used to do simulated operations in the virtual reality operation platform. RESULTS AND CONCLUSION:A case of Pilon fracture was simulated by using reverse engineering and virtual reality technology preoperatively. The processed 3D model was introduced into the virtual reality system to simulate the operation and help doctors choose the type, position and direction of the surgical approach and plate;the effect is good.
2.Preparation and in vitro evaluation of borneol and folic acid co-modified doxorubicin loaded PAMAM drug delivery system.
Jingjing LI ; Manman GUO ; Shunping HAN ; Yue SUN ; Weidong FEI ; Xiuiing XU ; Fanzhu LI
Acta Pharmaceutica Sinica 2015;50(7):899-905
A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.
3.Study regional homogeneity and low frequency amplitude of brain resting state functional magnetic resonance imaging in patients with depression
Bing ZHAO ; Xilin WANG ; Manman CHEN ; Ying LIU ; Han ZHANG ; Jinmin LIAO ; Yue GAO
Chinese Journal of Behavioral Medicine and Brain Science 2016;25(11):986-991
Objective To explore the abnormally functional brain regions of female patients with depression by resting state functional magnetic resonance imaging (fMRI),and analyze the correlation with the severity of depressive symptoms.Methods 32 female patients diagnosed with depressive disorder and 40 matched healthy controls completed resting state fMRI scans.The whole brain's regional homogeneity (ReHo) and amplitude of low-frequency fluctuation(ALFF) were calculated,and the correlation analysis be tween ReHo and ALFF of brain regions with significant difference and the severity of depressive symptoms was conducted.Results Compared with control group,the left precuneus/left cuneus (MNI:-18,-81,45),bilateral precentral gyrus (MNI:-58,-5,35 and 57,-6,33),left inferior parietal lobule (MNI:-42,-36,45) and right inferior temporal gyrus(MN1:60,-45,-18) (P<0.05,corrected by AlphaSim)in the case group showed significantly decreased ReHo,with statistical significance.Compared with control group,the left cuneus(MNI:-3,-87,30),right inferior temporal gyrus(MNI:60,-48,-18) and left precentral gyrus(MNI:-63,-3,26) (P<0.05,corrected by AlphasSim)in the case group showed significantly decreased ALFF.The ReHo in the right inferior temporal gyrus was negative correlated with the HAMD-17 total score and retarda tion factor(r=-0.484,P=0.017;r=-0.408,P=0.048),the ALFF in the right inferior temporal gyrus was positively correlated with weight factor(r=0.574,P=0.003),and negative correlated with the number of depressive episodes(r=-0.416,P=0.043).Conclusion Female with depression in resting state have several abnormally functional brain regions and the extent of damage is correlated with the severity of depressive symptoms.Combination of the two parameters may yield a more comprehensive pathophy-siological mechanism for depressive disorder.
4.Cognitive functions in patients with depressive disorder,hyperlipidemia disorder, and comorbid both of the disorders
Yuqing SONG ; Hongguang CHEN ; Jinmin LIAO ; Han ZHANG ; Manman CHEN ; Xilin WANG
Chinese Mental Health Journal 2018;32(2):112-117
Objective:To compare the cognitive functions in patients with depressive disorder,hyperlipidemia disorder,and comorbid both of the disorders.Methods:A cross-sectional study was performed in age,gender and education year matched patients with depressive disorder (n =51)(according to the ICD-10),hypedipidemia(n =38) (according to the Chinese adult lipid guideline),comorbid both of the disorders(n =40) and normal controls (n =56) were recruited in this study.All subjects received a battery of neuropsychological tests to access the anxiety and depression symptoms and cognitive function.Results:The scores of MoCA were lower in the patients with comorbid both disorders and patients with depression than patients with hypedipidemia [(24 ± 3),(24 ± 4)vs.(26 ± 3),Ps <0.05],and were lower in patients with depression than in normal controls(25 ±3),P <0.05.Stroop color test amends numbers were higher in patients with comorbid disorder than in the other three groups (Ps <0.05).The scores of immediate and delayed logical memory were higher in patients with hyperlipidemia than in other three groups (Ps <0.05).The total number of words in verbal fluency test were lower in patients with comorbid disorders and patients with depression than in patients with hyperlipidemia (Ps <0.05).Wisconsin card sorting test category completes were lower in patients with comorbid disorders and patients with depression than in patients with hyperlipidemia and normal controls (Ps < 0.05).The scores of persistent errors were higher in patients with comorbid disorders and patients with depression than in patients with hyperlipidemia and normal controls (Ps <0.05).Conclusion:In this study,patients with depressive disorder have impairment of cognitive function,while hyperlipidemia may probably do not impair cognitive function.
5.Changes of autophagy-related genes in the brains of the rats in the developmental stage with epilepsy
Qin-Rui LI ; Ying HAN ; Junbao DU ; Hongfang JIN ; Jing ZHANG ; Manman NIU ; Jiong QIN
Chinese Journal of Applied Clinical Pediatrics 2018;33(12):909-912
Objective To explore the changes of Beclin-1,P62/SQSTM1,microtubule-associated protein 1 light chain 3 (LC3)and unc-51 like autophagy activating kinase 1 (ULK-1)in the brains of the rats in the deve-lopmental stage with epilepsy. Methods Seventy-two male Sprague Dawley (SD)rats aged 21 days were randomly divided into the control group and the epilepsy group. The rats in 2 groups were randomly subdivided into 4 groups according to the time intervals (3 h,6 h,12 h and 48 h),respectively,with 9 rats in each group. The rats in the epilep-sy group were injected with kainic acid (12 mg/kg)to induce epilepsy,and the rats in the control group were injected with equal volume of saline. The rats in 2 groups were anaesthetized and sacrificed. Then,the brain tissues of the rats were quickly removed according to the time intervals. The brain damages were determined by adopting Nissl staining method. The apoptotic cells were detected by Terminal - deoxynucleoitidyl transferase mediated nick end labeling (TUNEL)assays. The expressions of Beclin-1,P62/SQSTM1,LC3 and ULK-1 mRNA levels in cortex were mea-sured by using real-time quantitative polymerase chain reaction (qPCR)analysis. Results Nissl staining indicated that many neurons were damaged performing vague outline,irregularly aligned,pyknotic nuclei and shrunken somata in the epilepsy 48 h group. In addition,there was a huge loss of neurons in cortex in the epilepsy 48 h group [(82 ± 8)num-bers],compared with the control group [(122 ± 8)numbers],and the difference was statistically significant (F=3. 768, P=0. 01). The apoptotic cells tremendously increased in the epilepsy 48 h group [(13 ± 7)numbers],compared with the control group [(2 ± 1)numbers]by TUNEL analysis,and the diffe-rence was statistically significant (t= -3. 821, P=0. 003). qPCR showed the mRNA levels of Beclin-1,P62/SQSTM1,LC3 and ULK-1 were upregulated in the epi-lepsy 12 h group (1. 70 ± 0. 75,1. 75 ± 0. 77,1. 52 ± 0. 43,7. 48 ± 6. 12)and the epilepsy 48 h group (1. 63 ± 0. 43, 1. 48 ± 0. 74,1. 74 ± 0. 55,7. 69 ± 5. 65),compared with the control group (1. 00,1. 00,1. 00,1. 00),and the differences were statistically significant (F=2. 820,3. 452,5. 811,5. 002,all P<0. 05). Conclusion The autophagy activates be-fore apoptosis occurs,and autophagy-related genes probably are involved in epilepsy-induced brain damage.
6.Honokiol attenuates mitochondrial fission and cell apoptosis by activating Sirt3 in intracerebral hemorrhage
Xuecheng ZHENG ; Junling GAO ; Manman ZHAO ; Lingling HAN ; Dexin ZHANG ; Kaijie WANG ; Jianzhong CUI
Chinese Medical Journal 2023;136(6):719-731
Background::Sirtuin-3 (Sirt3) has been documented to protect against mitochondrial dysfunction and apoptosis. Honokiol (HKL) is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders. The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage (ICH).Methods::An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia. PC12 cells were stimulated with hemin. For the in vivo investigation, the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits. Hematoxylin-Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis. Immunohistochemical staining was used to investigate the expression of Sirt3. Adenosine triphosphate (ATP) levels were quantified to assess mitochondrial dysfunction. Cell counting kit-8, lactate dehydrogenase assay, and flow cytometry were used to analyze cell vitality and apoptosis in vitro. Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1 (Drp1) localization to mitochondria. Western blot was applied to quantify the expression of Sirt3, Bax, Bcl-2, cleaved-caspase-3, Drp1, phosphorylation of Drp1 at serine-616, and phosphorylation of Drp1 at serine-637 in vivo and in vitro.Results::HKL treatment alleviated neurological deficits, attenuated the histopathological damage and cell apoptosis, and restored the decreased ATP levels in ICH rats. HKL improved cell survival rate, reduced cell apoptosis, and inhibited mitochondrial fission in PC12 cells. Moreover, both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616, and reduced phosphorylation of Drp1 at Ser637. Meanwhile, immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells. The phosphorylation and mitochondrial translocation of Drp1 were effectively reversed by HKL treatment. Importantly, the selective Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine suppressed these effects. Conclusion::Our findings demonstrated that HKL ameliorated ICH-induced apoptosis and mitochondrial fission by Sirt3, suggesting that HKL has immense prospects for the treatment of ICH.
7.Construction and verification of a fall fear risk prediction model for elderly patients after operation for intertrochanteric fracture of femur
Yumei ZHA ; Xue SHAN ; Manman LI ; Qian HAN ; Fei LI ; Min LI ; Na KONG
Chinese Journal of Practical Nursing 2024;40(14):1097-1104
Objective:To investigate the current situation of fall fear in elderly patients after operation of intertrochanteric fracture, analyze the influencing factors and build a prediction model.Methods:A prospective cohort study and convenient sampling method were used to select 303 elderly patients with intertrochanteric fracture after surgery in the Department of Orthopedics, Affiliated Hospital of Jining Medical University from January 2021 to December 2022 as the modeling group. According to the scores of fall fear when getting out of bed for the first time, they were divided into 211 cases in the fall fear group and 92 cases in the non-fall fear group. Multivariate Logistic regression was used to analyze the influencing factors of fall fear after operation of femoral intertrochanteric fracture in elderly patients, and a risk prediction score model was established. ROC curve was used to evaluate the differentiation of the model, calibration chart was used to evaluate the calibration degree of the model, and Bootstrap method was used for internal verification. Data of 81 elderly patients with intertrochanteric fracture treated from January to May 2023 were collected as a validation set for external verification of the model.Results:A total of 6 influencing factors were included in the prediction of fall fear risk model for elderly patients after operation of intertrochanteric fracture: gender ( OR = 3.229, 95% CI 1.672 - 6.401), number of co-existing diseases ( OR = 9.578, 95% CI 4.532 - 20.245), pain ( OR = 1.684, 95% CI 1.074 - 2.463), depression ( OR = 1.719, 95% CI 1.371 - 2.155), social support ( OR = 0.859, 95% CI 0.784 - 0.942), and ability to perform activities of daily living ( OR = 0.960, 95% CI 0.932 - 0.989) (all P<0.05). The area under ROC curve of the prediction model was 0.853, the sensitivity was 0.896, and the specificity was 0.663. The area under the externally verified ROC curve was 0.766, the sensitivity was 0.800, and the specificity was 0.645. The calibration curve was close to the reference curve in the model prediction, indicating that the model hasd a good prediction effect. Conclusions:The prediction effect of this model is good, and it can quickly predict the risk of fall fear in elderly patients after operation of intertrochanteric fracture, and provide a basis for medical personnel to provide timely intervention measures.
8.A new perspective on acute-on-chronic liver failure based on clinical outcome of dynamic classification criteria
Manman XU ; Ming KONG ; Yingying CAO ; Fang LIU ; Tao HAN ; Zhongping DUAN ; Yu CHEN
Chinese Journal of Hepatology 2020;28(4):319-325
Objective:To analyze the clinical characteristics among types of acute-on-chronic liver failure (ACLF) and explore the new classification criteria for judging the prognosis of acute-on-chronic liver failure, so as to provide a basis for the formulation of more precise therapeutic schedule.Methods:388 cases with ACLF diagnosed in two tertiary level hospitals were included. Patients demographic characteristics, clinical examination information, diagnostic and treatment process information were collected. Laboratory examination data of day 1, 3, 7, 14, 21, 28 and of week 12 or prior to discharge after improvement and at 24 h prior to liver transplantation or death from the diagnosis of ACLF were collected. According to the change trend of the patient's prothrombin activity (PTA), the changes within 4 weeks and 12 weeks were divided into: increased to > 40 %, increase but still ≤ 40%, progressively decreasing or not continuously rising. Moreover, the change trend of total bilirubin (TBil) was divided into: decreasing degree≥50%, decreasing degree < 50%, progressively increasing or not decreasing. Patients meeting the requirements of dynamic classification were screened. PTA and TBil variation tendency of each patient at week 4 and 12 was synthesized, and prognostic condition for dynamic classification was formulated. The clinical characteristics of ACLF patients were analyzed by χ2 test. Results:A total of 262 screened cases were enrolled. At the 4th week of the course of disease, 45% of the patients' PTA had increased to > 40%, and 40.8% of the patients' TBIL had decreased by 50%. When the course of disease was progressed to 12 weeks, 65.3% of the patients' PTA had increased to > 40%, and 63.4% of the patients' TBIL had decreased by 50%. Combined with the prognosis of the patients at the 4th and 12th week, the patients' disease evolution process was divided into five types: Type A: 60 cases (22.9%) of rapid progression; Type B: 82 cases (31.3%) of rapid recovery; Type C: 48 cases (18.3%) of slow progression; Type D: 43 cases (16.4%) of slow recovering; Type E: 29 cases (11.1%) of slow persistence. The proportions of patients with rapid progression combined with upper gastrointestinal hemorrhage, hepatic encephalopathy, and acute renal injury were 16.7%, 33.3%, and 33.3%, respectively; while the above-mentioned complications accounted for 3.7%, 7.3%, and 12.2% only in the rapid recovery type, χ2 = 14.411, 20.060, 12.140, P < 0.05, and the differences were statistically significant. Fungal infection rates were 21.7%, and 10.4% in patients who died of disease or liver transplantation (i.e., patients with rapid progression and slow-progressing types), respectively, and 1.2%, 14%, and 6.9% in patients with rapid progression type, slow-recovering type, and slow persistence type, respectively, and the difference between the rapid progression type and the rapid recovery type was significant, χ2 = 18.925, and the difference was statistically significant ( P < 0.05). Conclusion:The course of disease progression in ACLF patients can be divided into rapid progression type, rapid recovery type, slow progression type, slow recovering type, and slow persistence type. The basis of liver disease, accompanied with fungal infection, gastrointestinal hemorrhage, hepatic encephalopathy and acute renal injury can affect the development of ACLF.
9.Comparison of clinical features between patients with acute-on-chronic liver failure and decompensated liver cirrhosis combined with acute kidney injury
Weiwei KANG ; Liping DUAN ; Manman XU ; Ming KONG ; Yingying CAO ; Fang LIU ; Tao HAN ; Zhongping DUAN ; Yu CHEN
Chinese Journal of Hepatology 2020;28(5):391-396
Objective:To compare the clinical features between patients with acute-on-chronic liver failure (ACLF) and decompensated liver cirrhosis (DC) combined with acute kidney injury (AKI).Methods:Demographic data, clinical examination results, diagnosis and treatment information of ACLF and DC patients were collected retrospectively. Clinical characteristics of ACLF combined with AKI and DC combined with AKI and their impact on the 90-day mortality risk were compared.Results:The clinical characteristics of patients with ACLF-AKI and DC-AKI were compared. The results showed that the leukocyte count, absolute neutrophil count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) of ACLF-AKI patients were higher than those of DC-AKI patients, while prothrombin activity (PTA), and albumin were lower than those of DC-AKI patients, and the difference was statistically significant ( P < 0.05). The co-infection rate in patients with ACLF-AKI was significantly higher than that of DC-AKI group (96.9% vs. 39.5%) ( P < 0.05), and during the diagnosis of AKI, the median value of serum creatinine in ACLF patients was 147 μmol / L (IQR: 122-189), while that in DC group was 123.5 μmol / L (IQR: 103.8-155.5), and the difference between the two groups was statistically significant ( P < 0.05). According to the HRS-AKI diagnostic criteria for liver cirrhosis, 44 (68.8%) cases of ACLF-AKI met the diagnosis of HRS -AKI, which was significantly higher than the proportion of 18 (47.4%) cases of DC-AKI ( P < 0.05). Four (10.5%) cases of DC-AKI had died or underwent liver transplantation within 30 days and eight (21.1%) cases had died or underwent liver transplantation within 90 days, while 22 (34.4%) cases of ACLF-AKI patients had died or underwent liver transplantation within 30 days and 35 (54.7%) cases had died or underwent liver transplantation within 90 days, and χ2 values was 7.140 and 11.062, respectively ( P < 0.05). The results of multivariate regression analysis suggested that the independent risk factors that affect the 90-days mortality rate of DC patients were hepatic encephalopathy, gastrointestinal bleeding, and TBil, while the independent risk factors affecting the 90-days death risk of ACLF patients included AKI, PTA and TBil. Conclusion:Compared with DC-AKI patients, ACLF-AKI patients have a higher proportion of infection rate, higher serum creatinine level when diagnosed AKI, and faster disease progression, leading to a greater risk of death.
10.Physiological characteristics of Bacillus thuringiensis subspecies israelensis with double mutations of cwlE and sigK and its activity against larvae of Culex pipiens pallens
Lixin HUANG ; Guangjie HAN ; Chuanming LI ; Manman LIN ; Nan ZHANG ; Jian XU
Chinese Journal of Schistosomiasis Control 2024;36(6):606-613
Objective To investigate the physiological characteristics of Bacillus thuringiensis subspecies israelensis (Bti) with double mutations of cwlE and sigK genes and to assess the activity of Bti against larvae of Culex pipiens pallens under different external factors, so as to provide the theoretical evidence for the use of engineered bacteria of Bti for effective mosquito control. Methods B. thuringiensis wild-type strain Bt-59 and Bt-59 strain with cwlE mutation [Bt-59 (ΔcwlE)] were cultured in nutrient broth media for 24 hours, and Bt-59 strains with sigK mutation [Bt-59 (ΔsigK)] and double mutations of cwlE and sigK [Bt-59 (ΔcwlE-sigK)] were cultured in nutrient broth media for 48 hours. Then, 5 μL of culture media were transferred to glass sides, and cell morphology and mother cell lysis were observed under an optical microscope. The optical densities of Bti strain culture media were measured at different time points of culture, and the growth curves of Bt-59, Bt-59 (ΔcwlE), Bt-59 (ΔsigK), and Bt-59 (ΔcwlE-sigK) strains were plotted. The differences in carbon source metabolism of four Bti strains were analyzed using the Biolog microplate culture method, and the metabolic activity of these strains was estimated with average well color development (AWCD). The fermentation media of these four Bti strains were diluted into final concentrations of 2.000, 1.000, 0.500, 0.250, and 0.125 μL/L, and the median lethal concentrations (LC50 values) of these four strains against the third instar larvae of Cx. pipiens pallens were determined. In addition, the fermentation media of Bti strains were processed as follows: pH adjusted to 5, 7 and 9; treated at 30, 40 ℃ and 50 ℃ for 12 hours; and exposed to irradiation with ultraviolet lights for 0 hour and 6 hours. Then, 20 third instar larvae of Cx. pipiens pallens were exposed to the above processed fermentation media at a final concentration of 1 μL/L in 200 mL of water at 26 ℃ for 24 hours, and the mosquito mortality was estimated to evaluate the effects of pH, temperature and ultraviolet irradiation on the larvicidal activity of four Bti strains. Results The growth curves of the Bt-59 strain and its mutants shared a similar changing trend, and both experienced a stable phase 6 hours post-culture. Both spores and crystal proteins were found in Bt-59 and Bt-59 (ΔcwlE) cells, and only crystal proteins were found in Bt-59 (ΔsigK) and Bt-59 (ΔcwlE-sigK) cells. No lysis was found in the cell wall of the Bt-59 (ΔcwlE-sigK) strain, and the crystal protein was embedded in the mother cell. Biolog microplate culture assay showed that the AWCD values of four Bti strains showed a similar changing trend over time, and 33 carbon sources were found to be metabolized by all of the four strains, including dextrin, D-maltose and D-trehalose. The LC50 values of the fermentation media of Bt-59, Bt-59 (ΔcwlE), Bt-59 (ΔsigK), and Bt-59 (ΔcwlE-sigK) strains were 0.60, 0.51, 0.70 μL/L and 0.72 μL/L against Cx. pipiens pallens, respectively. The adjusted mortality of larval Cx. pipiens pallens reduced by 76.60%, 76.00%, 66.67%, and 0 following exposure to the fermentation media of Bt-59, Bt-59 (ΔcwlE), Bt-59 (ΔsigK), and Bt-59 (ΔcwlE-sigK) strains at a pH of 5 relative to at a pH of 7, and the adjusted mortality reduced by 49.02%, 51.06%, 36.36%, and 4.44% following 6-hour exposure to ultraviolet irradiation relative to 0-hour exposure, while the adjusted mortality was 68.33% to 83.33% following treatment with the fermentation media of four Bti strains at different temperatures. Conclusions Bt-59 (ΔcwlE-sigK) strains do not generate spores, and the absence of cwlE and sigK does not affect the growth, carbon source metabolism, and larvicidal activity of Bti strains against larval Cx. pipiens pallens. Cell wall embedding of Bt-59 (ΔcwlE-sigK) strains may protect larvicidal crystal proteins of Bti strains from external environmental factors, including ultraviolet irradiation, and pH alteration.