1.A real-world study of the clinical application of the Paris system for reporting urinary cytology in cancer hospital
Huan ZHAO ; Zhihui ZHANG ; Huiqin GUO ; Na WEI ; Haiyue MA ; Linlin ZHAO ; Yue SUN ; Cong WANG ; Xinxiang CHANG ; Xingang BI ; Nianzeng XING
Chinese Journal of Oncology 2024;46(7):703-709
Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P<0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P<0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.
2.Preparation of copolymer 7-hydroxyethyl chrysin loaded PLGA nanoparticles and the in vitro release
Xiaojuan WANG ; Baole YANG ; Chuan MA ; Lei HE ; Linlin JING ; Qiong HUANG ; Huiping MA
Journal of Zhejiang University. Medical sciences 2024;53(1):116-125
Objective:To prepare 7-hydroxyethyl chrysin(7-HEC)loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles and to detect the in vitro release.Methods:The 7-HEC/PLGA nanoparticles were prepared by emulsification solvent volatilization method.The particle size,polydispersity index(PDI),encapsulation rate,drug loading and zeta potential were measured.The prescription was optimized by single factor investigation combined with Box-Behnken response surface method.Mannitol was used as protectant to prepare lyophilized powder,and the optimal formulation was characterized and studied for the in vitro release.Results:The optimal formulation of 7-HEC/PLGA nanoparticles was as follows:drug loading ratio of 2.12∶20,oil-water volume ratio of 1∶14.7,and 2.72%soybean phospholipid as emulsifier.With the optimal formulation,the average particle size of 7-HEC/PLGA nanoparticles was(240.28±0.96)nm,the PDI was 0.25±0.69,the encapsulation rate was(75.74±0.80)%,the drug loading capacity was(6.98±0.83)%,and the potentiostatic potential was(-18.17±0.17)mV.The cumulative in vitro release reached more than 50%within 48 h.Conclusions:The optimized formulation is stable and easy to operate.The prepared 7-HEC/PLGA nanoparticles have uniform particle size,high encapsulation rate and significantly higher dissolution rate than 7-HEC.
3.A real-world study of the clinical application of the Paris system for reporting urinary cytology in cancer hospital
Huan ZHAO ; Zhihui ZHANG ; Huiqin GUO ; Na WEI ; Haiyue MA ; Linlin ZHAO ; Yue SUN ; Cong WANG ; Xinxiang CHANG ; Xingang BI ; Nianzeng XING
Chinese Journal of Oncology 2024;46(7):703-709
Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P<0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P<0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.
4.Role of cathepsin D in cardiovascular events following acute ST-segment elevation myocardial infarction
Journal of China Medical University 2024;53(10):929-933
Objective To determine the role of cathepsin D(CTSD)in cardiovascular events after acute ST-segment elevation myocar-dial infarction(STEMI).Methods A total of 96 patients with STEMI admitted to the Department of Cardiovascular Medicine of Second Hospital Affiliated to Shenyang Medical College from November 2022 to July 2023 were selected as the STEMI group.In addition,20 patients with normal coronary angiography hospitalized during the same period were selected as the control group.Coronary blood was collected from both groups,and the relative expression levels of CTSD in the arterial blood were detected and compared using real-time quantitative polymerase chain reaction.The STEMI group was divided into low,medium,and high CTSD groups based on CTSD expression,and major adverse cardiovascular events(MACE)that occurred within 6 months following percutaneous coronary interven-tion(PCI)were monitored.Results Arterial blood CTSD expression(1.31[1.03-1.75])in the STEMI group was higher than that in the control group(1.02[0.67-1.48])(P<0.05).Statistically significant differences in platelet count as well as troponin T,N-terminal pro-B natriuretic peptide,and high-density lipoprotein cholesterol levels were observed among the three groups(P<0.05).The incidence of MACE was significantly higher in the low CTSD group(65%)than in the high CTSD group(10%,P<0.05).Receiver operating cha-racteristic(ROC)curve analysis showed that the area under the ROC curve for predicting MACE within 6 months after PCI in patients with STEMI was 0.765(95%CI:0.658-0.872,P<0.001).Conclusion Whole blood CTSD expression level is abnormal in STEMI patient.CTSD may be an indicator for predicting the prognosis of STEMI and,therefore,a drug target for preventing and treating STEMI.
5.Survey on child health service capacity of community health institutions in Shenzhen city
Hongling MA ; Yang LIU ; Renping WANG ; Wenzhu LI ; Yucai ZHANG ; Linlin DONG ; Yuejie ZHENG
Chinese Journal of General Practitioners 2024;23(9):951-956
Objective:To survey the child health service capacity of community health service institutions in Shenzhen city.Methods:This was a cross-sectional study. An online survey was conducted among 559 community health service centers, stations and clinics in Shenzhen from January 23, 2024 to February 3, 2024. The questionnaire contents included the development of child health management, vaccination, diagnosis and treatment of common diseases in children, management of children′s chronic diseases, appropriate technology, availability of children′s special drug dosage forms, provision of special Chinese patent medicine and appropriate technology of traditional Chinese medicine for children, referral and remote consultation in 2019 and 2023. The reasons of unavailable service items were asked in the questionnaire and the questionnaire also contained an open-ended question about the suggestions for improving the capacity of child health services.Results:A total of 559 valid questionnaires were collected, accounting for 64.48% (559/867) of the community health service centers, stations and health clinics in Shenzhen in 2023. Compared to 2019, there was a significant increase in the rate of pediatric health services provided in 2023, including the diagnosis and treatment of common diseases in children under 6 years (96.06%, 537 institutions), nebulized inhalation therapy (96.60%, 540 institutions), influenza and other respiratory pathogen detection (90.70%, 507 institutions), rotavirus and other intestinal pathogen detection (34.53%, 193 institutions), allergen detection (81.75%, 457 institutions), blood oxygen saturation monitoring (84.44%, 472 institutions), pediatric-specific formulations of Western medicine (90.52%, 506 institutions), pediatric-specific formulations of traditional Chinese medicine (89.27%, 499 institutions), appropriate Chinese medicine techniques (88.19%, 493 institutions), relatively fixed referral hospitals (95.17%, 532 institutions), and remote consultation service (19.14%, 107 institutions); and the differences were statistically significant ( P<0.01). The reasons for unavailable service items were lack of space and personnel for the basic public health services, lack of space, personnel and a deficiency in knowledge and technical capabilities for diagnostic tests, and lack of equipment and personnel for remote consultation service. Suggestions made by 394 respondent institutions (70.48%) for further improvement included: conducting and strengthening various training (44.42%, 175/394), consultation and teaching by expert visiting (18.53%, 73/394), increasing the space and equipment (9.39%, 37/394), and further study at higher-level units (98.88%, 35/394). Conclusions:The child health services have been greatly improved in community health service institutions in Shenzhen, but there are still rooms for further improvement such as the ability of child health management, vaccination, chronic disease managements and provision of remote consultation.
6.Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention
Zhao BINBIN ; Wei DONGFENG ; Long QINGHUA ; Chen QINGJIE ; Wang FUSHUN ; Chen LINLIN ; Li ZEFEI ; Li TONG ; Ma TAO ; Liu WEI ; Wang LINSHUANG ; Yang CAISHUI ; Zhang XIAXIA ; Wang PING ; Zhang ZHANJUN
Journal of Pharmaceutical Analysis 2024;14(3):348-370
Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.
7.Establishment and evaluation of the nomogram prognostic model for oral squamous cell carcinoma
Journal of Practical Stomatology 2024;40(4):529-536
Objective:To investigate the prognostic factors of patients with oral squamous cell carcinoma(OSCC)and to establish a nomogram predictive model for the prediction of overall survival(OS)and disease-free survival(DFS)of the patients with OSCC.Methods:A retrospective analysis was performed on clinicopathological data of 361 OSCC patients underwent surgical treatment.Log-rank test and Cox regression model were used to analyze the prognosis of patients with OSCC.The nomogram was established based on the results of multivariate analysis and the consistency index(C index).Receiver operating characteristic curve(ROC)and calibration curve were used to evaluate the prediction ability and accuracy of the nomogram.Results:277 patients(76.73%)were followed up in this study.Univariate and multivariate analysis showed that age,perineural invasion,tumor differentiation and N stage were the inde-pendent risk factors for OS of patients,while age,perineural invasion,tumor differentiation and clinical stage were the independent risk factors for DFS of the patients(all P<0.05).The C index of the nomogram for OS and DFS of OSCC patients established by this method was 0.741 and 0.763,respectively.ROC and calibration curves showed that the OS and DFS models fitted well with the actual observa-tion results.Conclusion:The OS and DFS nomogram prognostic model of OSCC patients constructed based on age,perineural inva-sion,tumor differentiation,N stage and clinical stage has good predictive ability and accuracy,may help clinicians to accurately assess the prognosis of the patients,and have important significance for the individualized treatment of OSCC patients.
8.Synthesis,antioxidant and anti-hypoxia activities of 6-hydroxygenistein and its methylated derivatives
Pengpeng ZHANG ; Jie ZHANG ; Yiting TIAN ; Zhiqun SHI ; Huiping MA ; Linlin JING
Journal of Central South University(Medical Sciences) 2024;49(2):236-246
Objective:Hypoxia is a common pathological phenomenon,usually caused by insufficient oxygen supply or inability to use oxygen effectively.Hydroxylated and methoxylated flavonoids have significant anti-hypoxia activity.This study aims to explore the synthesis,antioxidant and anti-hypoxia activities of 6-hydroxygenistein(6-OHG)and its methoxylated derivatives. Methods:The 6-OHG and its methoxylated derivatives,including 4',6,7-trimethoxy-5-hydroxyisoflavone(compound 3),4',5,6,7-tetramethoxyisoflavone(compound 4),4',6-imethoxy-5,7-dihydroxyisoflavone(compound 6),and 4'-methoxy-5,6,7-trihydroxyisoflavone(compound 7),were synthesized by methylation,bromination,methoxylation,and demethylation using biochanin A as raw material.The structure of these products were characterized by 1hydrogen-nuclear magnetic resonance spectroscopy(1H-NMR)and mass spectrometry(MS).The purity of these compounds was detected by high pressure chromatography(HPLC).The antioxidant activity in vitro was investigated by 1,1-diphenyl-2-picrylhydrazyl radical(DPPH)free radical scavenging assay.PC12 cells were divided into a normal group,a hypoxia model group,rutin(1×10-9-1×10-5 mol/L)groups,and target compounds(1×10-9-1×10-5 mol/L)groups under normal and hypoxic conditions.Cell viability was detected by cell counting kit-8(CCK-8)assay,the target compounds with excellent anti-hypoxia activity and the drug concentration at the maximum anti-hypoxia activity were screened.PC12 cells were treated with the optimal concentration of the target compound or rutin with excellent anti-hypoxia activity,and the cell morphology was observed under light microscope.The apoptotic rate was determined by flow cytometry,and the expressions of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by Western blotting. Results:The structure of 6-OHG and its 4 methylated derivatives were correct,and the purity was all more than 97%.When the concentration was 4 mmol/L,the DPPH free radical removal rates of chemical compounds 7 and 6-OHG were 81.16%and 86.94%,respectively,which were higher than those of rutin,the positive control.The removal rates of chemical compounds 3,4,and 6 were all lower than 20%.Compared with the normal group,the cell viability of the hypoxia model group was significantly decreased(P<0.01).Compared with the hypoxia model group,compounds 3,4,and 6 had no significant effect on cell viability under hypoxic conditions.At all experimental concentrations,the cell viability of the 6-OHG group was significantly higher than that of the hypoxia model group(all P<0.05).The cell viability of compound 7 group at 1×10-7 and 1×10-6 mol/L was significantly higher than that of the hypoxia model group(both P<0.05).The anti-hypoxia activity of 6-OHG and compound 7 was excellent,and the optimal drug concentration was 1×10-6 and 1×10-7 mol/L.After PC12 cells was treated with 6-OHG(1×10-6 mol/L)and compound 7(1×10-7 mol/L),the cell damage was reduced,the apoptotic rate was significantly decreased(P<0.01),and the protein expression levels of HIF-1α and VEGF were significantly decreased in comparison with the hypoxia model group(both P<0.01). Conclusion:The optimized synthesis route can increase the yield of 6-OHG and obtain 4 derivatives by methylation and selective demethylation.6-OHG and compound 7 have excellent antioxidant and anti-hypoxia activities,which are related to the structure of the A-ring ortho-triphenol hydroxyl group in the molecule.
9.Application and prospect of image registration technology in the diagnosis and treatment of temporomandibular joint disor-ders
Yuting XIE ; Wen TANG ; Yue WU ; Libo CAO ; Jiajun MA ; Iman IZADIKHAH ; Yan CHEN ; Dan CAO ; Bin YAN ; Linlin ZHU ; Lizhe XIE
STOMATOLOGY 2024;44(10):770-774
With advancements in radiology,endoscopic techniques,surgical treatments,cell biology and molecular biology,the un-derstanding of temporomandibular disorders(TMD)has increased.The temporomandibular joint(TMJ)is a complex structure comprising both soft and hard tissues.Within the TMJ,the temporomandibular disc is a soft tissue structure that connects the mandible to the skull,providing cushioning and stability during joint movement.Different imaging techniques have their own advantages and limi-tations in the diagnosis and treatment of TMD.Therefore,using image registration technology to assess the condition and position of the articular disc provides new research perspectives for evaluating TMD,which may contribute to the diagnosis and treatment.This article reviews the latest advancements in TMJ imaging,explores the applications of various image registration techniques,particularly in the context of TMD diagnosis and treatment,and discusses future prospects.Combining the research results of some scholars at home and a-broad with the author’s clinical experience,the article aims to provide valuable insights for clinicians.
10.Effect of Early Intervention of Yishen Huazhuo Prescription on Learning and Memory of Accelerated Aging SAMP8 Mice and Its Mechanism
Shujie ZAN ; Kai WANG ; Jiachun XU ; Weiming SUN ; Daoyan NI ; Linlin ZHANG ; Shuang LIU ; Yan MA ; Pengjuan XU ; Lin LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):91-99
ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription (YHP) on the learning and memory of accelerated aging model mice, as well as its underlying mechanism. MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups, including the model group, low-dose YHP group, high-dose YHP group, and donepezil group. Additionally, 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group, each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg-1 and 12.48 g·kg-1, while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial (MG) polarization marker inducible nitric oxide synthase (iNOS) and M2 MG polarization marker arginase-1 (Arg-1) in the hippocampus region. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of pro-inflammatory factor interleukin 1β (IL-1β) and anti-inflammatory factor transforming growth factor-β1 (TGF-β1). Furthermore, Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 (Aβ1-42) along with triggering receptor expressed on myeloid cells 2 (TREM2)/nuclear factor kappa B (NF-κB) signaling pathway-related proteins TREM2, phospho (p)-NF-κB p65, and phospho-inhibitory kappa B kinase β (IKKβ) in the hippocampus. ResultCompared with the control group, the model group exhibited a significantly prolonged escape latency (P<0.01), a significant reduction in neuron-specific nuclear protein (NeuN) expression in the hippocampus, a significant increase in iNOS expression in MG, and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased, while the TGF-β1 content was significantly decreased. Additionally, there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions (P<0.05, P<0.01). However, no significant changes were observed in escape latency, times of crossing the platform, and hippocampal NeuN expression in the YHP treatment control group. Conversely, iNOS expression in MG as well as the hippocampal p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions were significantly decreased. Furthermore, TREM2 expression was significantly increased (P<0.05, P<0.01). In comparison to the model group, the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform (P<0.05, P<0.01). In the high-dose YHP group, the escape latency was significantly shortened (P<0.05). In the low-dose YHP group, high-dose YHP group, the expression of NeuN in the hippocampus was significantly increased, the expression of iNOS in MG was significantly decreased, and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased, while the TGF-β1 content was significantly increased. Furthermore, the expression of TREM2 in the hippocampus was significantly increased, and the expressions of p-NF-κB p65, p-IKKβ, and Aβ1-42 were significantly decreased (P<0.01). ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway, reduce the release of neuroinflammatory factors, protect hippocampal neurons, and reduce the deposition of Aβ1-42, and finally delay the occurrence of learning and memory decline in SAMP8 mice.

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