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2023 Vol. 53, No. 9
Published: 2023-09-25
689
The reduction of brain volume ratio in different regions is associated with early Alzheimer’s disease
WANG Zhen, WANG Yan, ZHANG Mengli, ZHU Hanyu, Pan Zhiming, HUANG Guiqian, WEN Caiyun, XIONG Li, SHI Lin
DOI: 10.3969/j.issn.2095-9400.2023.09.001
Objective: AccuBrain
®
, an automatic brain volume analysis software based on 3D magnetic resonance imaging (MRI), was used to explore the differences in the volume ratios of each brain region in patients with early Alzheimer’s disease (AD). Methods: Twenty-nine patients with early AD and 20 healthy controls from the First Affiliated Hospital of Wenzhou Medical University during January 2018 to December 2020 were enrolled. Mini-mental state examination (MMSE), activity of daily living scale (ADL-MBI) and clinical dementia rating (CDR) were used for neuropsychological assessment. The new automatic segmentation software AccuBrain
®
was used to accurately calculate the volume ratio of each region in the brain. The volume ratios of different brain regions of the two groups were analyzed by t test, rank sum test and collinearity analysis. The different brain regions and regions of interest were selected for binary Logistic regression and receiver operating characteristic (ROC) curve joint diagnostic analysis. Results: Compared with the control group, the early AD patients had significant brain volume differences in bilateral hippocampus, amygdala, and inferior horn of lateral ventricle. After adjusting the confounding factors, it was found that the brain volume of right hippocampus, right occipital lobe atrophy, right cingulate gyrus, left inferior horn of lateral ventricle, and left insular lobe atrophy could be used for the diagnosis of early AD (AUC=0.919). Meamwhile, regions of interest (ROI) 1-5 were selected,and Logistic regression was used to establish models 1-5 to obtain predictive values and draw ROC curves. The AUC was 0.867, 0.860, 0.843, 0.876, 0.893, respectively. Conclusion: Multiple brain regions atrophy occurs in early AD patients. Cognitive decline is associated with atrophy of the medial temporal lobe and gray matter volume in the prefrontal lobe, occipital lobe, insular lobe, and cingulate gyrus. The right hippocampus plays an important role in the combined diagnosis. AccuBrain
®
technology can assist in the early clinical diagnosis of AD.
2023 Vol. 53 (9): 689-697 [
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689
Development and validation of the multiplex immunoassay of serum markers for liver cancer: receptor tyrosine kinase AXL, cartilage oligomeric matrix protein and osteopontin
LI Siping, HAN Jinyu, HU Di, WANG Yajie, YU Xiaobo
DOI: 10.3969/j.issn.2095-9400.2023.09.002
Objective: To develop a multiplex immunoassay of serum receptor tyrosine kinase AXL,cartilage oligomeric matrix protein (COMP) and osteopontin (OPN) for liver cancer detection. Methods: We developed a multiplex immunoassays containing alpha-fetoprotein (AFP), AXL, COMP and OPN using flow cytometry, which was tested on their performance in detecting liver cancer patients from two clinical cohorts.Results: The detection range for AFP, AXL, COMP and OPN was respectively 0.046-100.000, 0.014-30.000,0.007-15.000 and 0.023-50.000 ng/mL while the 1imit of detection was 0.010 ng/mL for AFP, 0.014 ng/mL for AXL, 0.004 ng/mL for COMP and 0.007 ng/mL for OPN. The intra-assay and inter-assay were below 8% and 5%, respectively. The recovery rate was 84%-101%, and the linearity was 95%-102%. The measurement for AXL, COMP and OPN showed that there was no significant cross-talking reaction. There was a high correlation between flow immunoassay and clinical chemiluminescence immunoassay (r=0.995, P<0.001). The level of AFP,AXL, COMP and OPN in liver cancer was all higher than that in healthy control, and the difference was statistically significant (P<0.01). In all serum samples (n=100), when receiver operating characteristic (ROC) curve was plotted for liver cancer versus healthy control, among the single markers, serum OPN with AUC 0.913 had the best diagnosis performance for liver cancer. The combination of AFP, AXL, OPN with area under the curve (AUC) 0.937 and the combination of four markers with AUC 0.940 had comparable diagnosis performance. Finally,AFP, AXL and OPN were used to generate liver cancer prediction model. Conclusion: We have successfully developed the assays for detecting four serum markers in HCC. AXL, COMP and OPN are potent serum markers for detection of liver cancer, and the liver cancer prediction model based on the combined of AXL, OPN and AFP showed excellent diagnostic performance. The results have important reference value for the further development of multiplex assay reagents for other markers.
2023 Vol. 53 (9): 689-705,713 [
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706
Preparation of intelligent responsive anti-infection coating based on hyaluronidase activity
HUANG Yixing, ZHENG Zhenyu, XU Guochao, ZOU Shengtao.
DOI: 10.3969/j.issn.2095-9400.2023.09.003
Objective: To prepare an anti-infection coating on the surface of bone implants that can achieve enzyme and bacterial responsive release of antibiotics. Methods: After the (MMT/HA-VA)5 coating structure was successfully loaded on the substrate surface by layer-on-layer assembly technology, the variation in surface roughness was observed; and after contact with bacteria and enzymes, the surface morphology, the size of antibacterial ring and the thickness of coating were observed. The antibacterial effect of multilayer coatings was evaluated by detecting the bacterial contents. Its biocompatibility and antibacterial effect in vivo were tested by cell and animal experiments. Results: As the antibacterial coating was assembled, the surface roughness of (MMT/HA-VA)5 coating increased compared with that of (MMT/HA-VA)1 coating (P<0.05). The coating was disintegrated to varying degrees after contact with enzymes or bacteria, and the changes in bacteriostasis ring and coating thickness also showed a concentration dependence (P<0.05). At each time point, the content of extracellular alkaline phosphatase, potassium ion, protein and nucleic acid in (MMT/HA-VA)5 group was higher than in the blank group. Cytocompatibility test showed that the coating extract had no significant adverse effect on the actin filament and nucleus of MC3T3 cells. In the in vivo experiment, there were significant differences on TNF-α level between the infection group and (MMT/HA-VA)5 group (P<0.05). However, there was no significant difference in TNF-α level between the (MMT/HA-VA)5 group and the blank group (P>0.05). A large number of bacteria were detected on the surface of Kirschner’s needles in the infection group, but neither in the (MMT/HA-VA)5 group nor in the blank group. HE staining of bone tissue showed a large number of inflammatory cells in the infection group, while the bone structure of the (MMT/HA-VA)5 group and the blank group was normal.Conclusion: The (MMT/HA-VA)5 composite multilayer antibacterial coating can automatically adjust the dosage of antibiotic sustained release according to the severity of infection, thus achieving precise prevention and efficient sterilization of infections related to bone implants.
2023 Vol. 53 (9): 706-713 [
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714
The effect of electrical stimulation on the cellular localization of HDAC4 protein in early denervated muscular atrophy and its related mechanisms
PAN Lulu, LIN Sujin, JIANG Xujian, CHEN Wenyu,ZHANG Guowei, ZHI Yinghao
DOI: 10.3969/j.issn.2095-9400.2023.09.004
Objective: To explore the effect of electrical stimulation on the cellular localization of HDAC4 protein in early denervation atrophy and its possible mechanism. Methods: SD rats were randomly divided into four groups: normal control group (NC group), simple atrophy model group (MA group), atrophy+ low-frequency electrical stimulation group (20 Hz, LE group), and atrophy+high-frequency electrical stimulation group (100 Hz, HE group), with n=6 in each group. After 8 days of experimentation, the gastrocnemius muscle tissue of the right hind limb was collected for measurement. The average cross-sectional area (CSA) of muscle fibers was detected by immunofluorescence staining, the ultrastructure of muscle fibers and mitochondria was observed by transmission electron microscopy, cAMP concentration was detected by ELISA, Ca
2+
concentration was detected by colorimetry, and the total protein expression of CaMKII, PKA, HDAC4 and the expression of nuclear and cytoplasmic proteins were detected by Western blot. Results: Compared with the NC group, the relative weight and CSA of gastrocnemius muscle in the MA group decreased (P<0.05), and the electron microscopy showed disordered arrangement of muscle fibers and degeneration of mitochondria. The total protein and nuclear
protein expression of HDAC4 in the MA group were higher than those in the NC group (P<0.05), while the cytoplasmic protein expression of HDAC4 showed no significant difference. The expression of Ca
2+
concentration and CaMKII was decreased (P<0.05), while the expression of cAMP and PKA was increased (P<0.05). Compared with the MA group, the relative weight, CSA, Ca
2+
concentration, cytoplasmic protein expression of HDAC4,and CaMKII protein expression in the HE group were increased (P<0.05), so were the nuclear protein expression of HDAC4 and the expression of cAMP and PKA (P<0.05), while the total protein expression of HDAC4 showed no significant difference. Compared with the MA group, the only significantly increased indicators in the LE group were Ca
2+
concentration and CaMKII expression (P<0.05), and the other indicators showed no significant difference. Conclusion: Muscle atrophy can occur early after denervation, and the nuclear accumulation of HDAC4 may be an important factor affecting muscle atrophy. High-frequency electrical stimulation (100 Hz) may reduce the nuclear accumulation of HDAC4 by increasing the expression of molecules related to the Ca
2+
/CaMKII axis and decreasing the expression of molecules related to the cAMP/PKA axis, thereby reversing muscle atrophy.
2023 Vol. 53 (9): 714-720,728 [
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721
Predicting Ki-67 expression level in laryngeal squamous cell carcinoma based on dual energy CT parameters and clinical pathological feature nomogram
ZHENG Pengwei, LIN Guihan, CHEN Weiyue,CHEN Chunmiao, YING Haifeng, JI Jiansong.
DOI: 10.3969/j.issn.2095-9400.2023.09.005
Objective: To assess the predictive value of a nomogram based on dual-energy CT parameters and clinicopathological features in the preoperative prediction of the Ki-67 expression level in patients with laryngeal squamous-cell carcinoma (LSCC). Methods: A total of 96 LSCC patients who underwent dual-energy CT examination and were pathologically confirmed at the Fifth Affiliated Hospital of Wenzhou Medical University between January 2019 and December 2021 were included. They were randomly divided as training set (67 cases) and validation set (29 cases) at a ratio of 7:3. Patients were classified into Ki-67 high-expression group and Ki-67 low-expression group based on immunohistochemistry results. The clinicopathological features for analysis included age, gender, smoking history, tumor location, clinical T stage, degree of differentiation, and CT-reported lymph node status. Dual-energy CT parameters consisted of standardized iodine concentration (NIC) and energy
spectrum curve slope during arterial and venous phases (λ
HU
) and normalized effective atomic number (nZ
eff
).Logistic regression analysis was performed to identify independent risk factors influencing Ki-67 high expression in LSCC patients. Subsequently, a combined model was developed to integrate clinicopathological features and dual-energy CT parameters, and a nomogram was generated. The performance of the nomogram was evaluated using receiver operating characteristic curve and calibration curve. The clinical utility was assessed using decision curve analysis. Results: In the training set, significant differences were observed in CT-reported lymph node status and differentiation degree between the two groups (all P<0.05). The arterial phase NIC, λ
HU
, nZ
eff
, as well as the venous phase NIC, were significantly higher in the Ki-67 high-expression group than in the Ki-67 lowexpression group (all P<0.05). Multifactorial Logistic regression analysis identified CT-reported positive lymph node (OR=10.219, 95%CI=1.591-65.651), low degree of differentiation (OR=3.555, 95%CI=1.165-10.852), high arterial phase NIC (OR=5.592, 95%CI=1.583-19.751), and high arterial phase nZ
eff
(OR=9.943, 95%CI=1.999-49.450) as independent risk factors for predicting Ki-67 high expression. The nomogram constructed based on the above four indicators exhibited a high predictive performance with area under the curve of being 0.939 and 0.875 in the training set and validation set, respectively. The calibration curve and decision curve analysis demonstrated the robustness and clinical utility of the nomogram. Conclusion: The nomogram based on dualenergy CT parameters and clinicopathological features has significant predictive value in determining Ki-67 expression in patients with LSCC.
2023 Vol. 53 (9): 721-728 [
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Angiotensin II inhibits ZO-1 expression in endothelial cells by down-regulating VE-cadherin
SHEN Hongfeng, CHA Wei, JIN Zhijiang, XIA Haijiang, LIU Longbin.
DOI: 10.3969/j.issn.2095-9400.2023.09.006
Objective: To explore the mechanism by which angiotensin (Ang II) disrupts microvascular permeability. Methods: The primary culture and identification of rat endothelial cells were conducted, and cells in passage 4-7 used for the experiment were divided as the control, Ang II and Ang II+valsartan groups; real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to test the expression of zonula occludens-1 (ZO-1) and vascular endothelial (VE)-cadherin in the cells; the distribution of ZO-1 protein was detected by immunofluorescence assay. After transfection of VE-cadherin into endothelial cells, the cells were
divided as the control, Ang II and Ang II+VE-cadherin groups. The expression and distribution of ZO-1 protein were also detected. Results: Compared with the control group, the expression of ZO-1 and VE-cadherin in Ang II group was significantly decreased in mRNA level and protein level (both P<0.01). Additionally, the peripheral
positioning of ZO-1 protein in cell membrane was remarkably depressed. However, over-expression of VEcadherin by transfecting over-expression plasmid could significantly reverse the expression and distribution of ZO-1 in Ang II-treated endothelial cells. Conclusion: Ang II inhibited the expression of ZO-1 protein in vascular
endothelial cells by down-regulating VE-cadherin, thus destroying the tight junction between endothelial cells,which may be the possible mechanism by which Ang II disrupts microvascular permeability.
2023 Vol. 53 (9): 729-733 [
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178
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734
The value of serum soluble trigger receptor expressed myeloid cell-1, procalcitonin and lactate in evaluating short-term prognosis of patients with severe pneumonia
FU Shunjin, LIAO Qiming, JIN Jianmin
DOI: 10.3969/j.issn.2095-9400.2023.09.007
Objective: To explore the value of serum soluble trigger receptor expressed myeloid cell-1 (sTREM-1), procalcitonin (PCT) and lactate levels in evaluating the short-term prognosis of patients with severe pneumonia. Methods: A total of 198 patients with severe pneumonia confirmed in Jinhua People’s Hospital from October 2021 to December 2022 were included. According to the clinical outcome after 28 days of treatment,they were divided as the survival group (n=153) and the death group (n=45). The clinical data (gender, age,admission APACHE II and SOFA scores, proportion of septic shock) and blood biochemistry (admission time and 7 days after treatment) including sTREM-1, PCT, lactate, neutrophil to lymphocyte ratio (NLR), blood creatinine and urea nitrogen, C-reactive protein (CRP), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), platelet to lymphocyte ratio (PLR) were compared. Multivariate Logistic regression was used to screen influencing factors,Spearman correlation analysis to analyze correlation, receiver operator characteristic curve (ROC) to calculate area under curve (AUC) and optimal critical value, Kaplan-Meier curve to plot cumulative survival rate. Results:The scores of APACHE II and SOFA, septic shock, sTREM-1, PCT, lactic acid, NLR, serum creatinine and urea nitrogen, CRP, IL-8 and TNF-α admission in the death group were significantly higher than in the survival group, while PLR was significantly decreased (P<0.05). Multivariate Logistic regression showed that the higher APACHE II score and increased sTREM-1, PCT and lactic acid were closely related to the 28-day death of severe pneumonia (P<0.05). Spearman correlation analysis showed that APACHE II score was significantly positively correlated with sTREM-1, PCT and lactate levels (r=0.620, 0.595 and 0.521, P<0.05). ROC showed AUC of sTREM-1, PCT and lactic acid for predicting death was 0.801, 0.698 and 0.745 respectively. AUC of sTREM-1 combined with lactic acid for predicting death was 0.899, with the cut-off value of sTREM-1≥35.6 mmol/L and lactic acid≥1.68 mmol/L, respectively. A total of 198 patients were divided into high-risk group (n=59,sTREM-1≥35.6 mmol/L and lactic acid≥1.68 mmol/L), medium-risk group (n=50, sTREM-1≥35.6 mmol/L or lactic acid≥1.68 mmol/L) and low-risk group (n=89, sTREM-1<35.6 mmol/L and lactic acid<1.68 mmol/L).The Kaplan-Meier survival curve showed that cumulative survival rate of high-risk group was the lowest (P<0.05). Conclusion: Early detection of sTREM-1, PCT and lactic acid for severe pneumonia is of great value in evaluating clinical outcome after 28-day treatment. sTREM-1 combined with lactic acid is the most valuable in predicting death, and sTREM-1≥35.6 mmol/L and lactic acid≥1.68 mmol/L are critical values.
2023 Vol. 53 (9): 734-739 [
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219
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740
The correlation between reduced serum uric acid levels and cognitive impairment in patients with depressive disorder
HUANG Ziye, ZHENG Ke, CHEN Ce, TU Wenzhen
DOI: 10.3969/j.issn.2095-9400.2023.09.008
Objective: To explore the changes in serum uric acid (SUA) levels and their relationship with cognitive impairment in patients with depression. Methods: A total of 110 depressive patients and healthy adults were recruited from January 2022 to December 2022 at the Seventh People’s Hospital of Wenzhou, who were divided as depression group (55) and a healthy control group (55). Repeatable Battery for the Assessment of Neuropsychological (RBANS) was used to assess the cognitive functions of the two groups, including immediate memory, visuospatial, language function, attention function, delayed memory, and SUA levels were also estimated. Results: After controlling covariates, the SUA levels, immediate memory, attention function, language function, delayed memory, and total RBANS score of the depression group were lower than those of the control group, with statistically significant difference (P<0.05). After Bonferroni correction, there were still significant differences between the two groups in immediate memory, language function, and attention (P<0.05). There was a positive correlation between SUA levels and immediate memory (r=0.315, P=0.019), attention function (r=0.401, P=0.002), language function (r=0.353, P=0.008), delayed memory (r=0.412, P=0.002), and RBANS total score (r=0.397, P=0.003) in the depression group. Multiple linear regression suggested a positive correlation between SUA levels and language (B=0.127, P=0.044) and attention function (B=0.166, P=0.036) in patients with depression.Conclusion: Our results suggest that reduced SUA levels might be implicated in the pathophysiology of cognitive impairment in depressive disorder.
2023 Vol. 53 (9): 740-743,748 [
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375
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744
Effect of lateral meniscus posterior root tears at different positions on tibiofemoral joint under knee extension
ZHAO Zhangwei, WANG Juncheng, DONG Yilong, CAI Chunyuan
DOI: 10.3969/j.issn.2095-9400.2023.09.009
Objective: To measure the effect of lateral meniscus posterior root (LMPR) tears at different positions on the both tibiofemoral compartments. Methods: Twelve cadaveric knees were tested under a 1 kN axial load at flexion angles 0°. The contact area and average contact pressure of both tibiofemoral compartments were
measured under 5 lateral meniscus conditions: intact, root avulsion, serial radial tear at 3 mm, 6 mm from the root attachment site, and total meniscectomy. Results: In the lateral compartment, the average contact pressure was (0.68±0.07)MPa and the contact area was (454.49±32.55)mm2 when the meniscus was intact. The lateral
meniscus posterior root (LMPR) avulsion and radial tear of 3 mm, 6 mm from the root attachment site resulted in significantly decreased contact area and increased average contact pressure of the lateral compartment, compared with the intact state (P<0.01). There was no difference among the three groups (P>0.05). Meniscectomy produced higher decreases than root tear in contact area and increases in average pressure (P<0.05). In the medial compartment, average contact pressure was (0.72±0.06)MPa and the contact area was (470.99±33.64)mm2 when the meniscus was intact. The lateral meniscus posterior root (LMPR) avulsion and radial tear had no effect on the average contact pressure or contact area of the medial compartment, but total lateral meniscectomy would reduce the contact area (P<0.01). Conclusion: The lateral meniscus posterior root (LMPR) avulsion and radial tear can significantly increase the average contact pressure and reduce the contact area of the lateral compartment, but there is no difference among the tears at three different positions in the experiment. Total lateral meniscectomy will further enhance the changes of the above indexes of the lateral compartment and reduce the contact area of the medial compartment
2023 Vol. 53 (9): 744-748 [
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749
Application of data mining technology in constructing self-management association rules for patients with non-alcoholic fatty liver disease
LIN Xiuli, BAO Shaorui, HUANG Haiping, SHU Meichun
DOI: 10.3969/j.issn.2095-9400.2023.09.010
Objective: To explore factors associated with the self-management ability of patients with non-alcoholic fatty liver disease (NAFLD) and to provide the basis for patients to develop reasonable selfmanagement plans. Methods: Collecting the baseline data of 241 NAFLD patients admitted to the First Affiliated Hospital Wenzhou Medical University from November 2020 to September 2021, including marital status, smoking history, education level, body mass index, fatty liver degree, etc. and their self-management ability. The researchers utilized the Apriori algorithm to mine frequent itemsets of association rules, analyze patient-related data and extract itemsets related to self-management from the database. Subsequently, association rules were constructed. Results:The self-management score of patients ranged from 60 to 130 points, with an average of (91.24±16.98) points,which were divided into high, medium and low levels. With conditions set, a total of 1 322 rules were screened
out through chi-square tests. Considering patient factors, clinical practice and professional nursing knowledge,the researchers decided on nine rules that were directly associated with self-management ability. Conclusion:The findings suggest that variables such as body mass index, number of comorbidities with chronic diseases,
degree of fatty liver disease, smoking history, marital status, and educational level are correlated with the selfmanagement ability of NAFLD patients. Therefore, it is recommended that patients from different cultural backgrounds adopt personalized education programs. Additionally, active involvement of family members in weight control and smoking cessation is encouraged to improve patients’ self-management ability and enhance the prognosis of NAFLD patients.
2023 Vol. 53 (9): 749-753 [
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761
Advances in the study of kisspeptin in assisted reproduction
SUN Yiqun, ZHAO Junzhao
DOI: 10.3969/j.issn.2095-9400.2023.09.013
Kisspeptin is a neuropeptide that regulates female reproduction by binding to the G proteincoupled receptor KISS1R and stimulating gonadotropin-releasing hormone release, which in turn regulates the hypothalamic-pituitary-gonadal axis. In addition to the hypothalamus, kisspeptin and its receptor KISS1R are also found to be expressed in the ovary, endometrium, trophectoderm and other tissues and cells. The locally expressed kisspeptin/KISS1R involved in a variety of physiological activities is significant for oocyte maturation and embryo implantation. In this paper, we review the progress of kisspeptin in reproduction-related fields,particularly ovulation and implantation, and briefly discuss kisspeptin’s potential significance in predicting pregnancy outcome and reproduction-related diseases such as recurrent transfer failure and recurrent miscarriage,in order to provide ideas for kisspeptin’s application in assisted reproductive technology.
2023 Vol. 53 (9): 761-767 [
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212
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768
Research progress of laparoscopic partial nephrectomy assisted by robotic surgery system
WANG Shuaibin, FAN Lailai, YU Haifeng, HE Youhua
DOI: 10.3969/j.issn.2095-9400.2023.09.014
Renal tumor is the common neoplasm in genitourinary system. As the proportion of patients with early renal tumors detected by medical imaging examination increases year by year, partial nephrectomy is also increasing. Nowadays, robot-assisted partial nephrectomy (RAPN) has been widely used in PN. With the expanded three-dimensional vision, multi-angle precise dissection of renal tumors and rapid suture, RAPN has reduced the intraoperative blood loss and shortened the time of renal warm ischemia. RAPN has become a new surgical choice for patients with renal tumors. This article reviews the current status and development of the application of RAPN in recent years.
2023 Vol. 53 (9): 768-774,封三 [
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