1.Value of APTw imaging combined with DCE-MRI quantitative parameters for preoperative assessment of Her-2 gene expression in endometrial cancer
Changjun MA ; Shifeng TIAN ; Qingling SONG ; Lihua CHEN ; Nan WANG ; Qingwei SONG ; Ailian LIU
Chinese Journal of Radiology 2024;58(6):620-626
Objective:To investigate the value of quantitative parameters of amide proton transfer-weighted (APTw) imaging and dynamic contrast-enhanced (DCE)-MRI for preoperative assessment of human epidermal growth factor receptor 2 (Her-2) gene expression in endometrial cancer (EC).Methods:This research conducted a diagnostic pilot study involving 68 patients with pathologically confirmed EC at the First Hospital of Dalian Medical University from August 2019 to August 2023. Patients were categorized into Her-2-positive group (33 cases) and Her-2-negative group (35 cases) based on postoperative Her-2 gene expression results. Utilizing the APTw and DCE-MRI sequences, quantitative parameters including the asymmetric magnetization transfer ratio (MTR asym) for APTw and the volumetric transfer constant (K trans), plasma volume fraction (V p), extracellular mesenchymal space (V e), and rate constant (K ep) for DCE-MRI were acquired for the lesion site. Statistical differences in the values of each quantitative parameter between the two groups were evaluated using two independent sample t test or Mann-Whitney U test. The study incorporated quantitative parameters and clinicopathological data of patients to identify independent predictors of EC Her-2 gene expression through logistic regression analysis. A diagnostic model was developed using binary logistic regression analysis. The effectiveness of the parameters and diagnostic model was evaluated using receiver operating characteristic curves. DeLong test was used to compare the differences between the areas under the curves (AUC). Results:The study found statistically significant differences in MTR asym, K trans, and V e between the Her-2-positive group and the Her-2-negative group ( Z=2.55, P=0.011; t=-2.03, P=0.047; t=-2.13, P=0.037). However, the differences in V p and K ep were not statistically significant ( Z=0.58, P=0.560; Z=0.19, P=0.849). MTR asym emerged as a significant independent predictor of Her-2 gene expression in EC ( OR=1.016, 95% CI 1.003-1.030, P=0.014). Incorporating MTR asym, K trans, and V e, the diagnostic model yielded an AUC (95% CI) of 0.745 (0.625-0.864). The AUC (95% CI) for MTR asym, K trans, and V e alone were 0.680 (0.551-0.808), 0.623 (0.485-0.760), and 0.656 (0.523-0.789) respectively. The differences in AUC between the diagnostic model and individual predictors MTR asym, K trans, and V e were not found to be statistically significant ( Z=1.40, 1.92, 1.37, P=0.163, 0.055, 0.171). Conclusion:The quantitative parameters of APTw and DCE-MRI sequences can preoperatively assess EC Her-2 gene expression from a different perspective, with MTR asym potentially serving as a valuable independent predictor.
2.Relationship between serum HMGB1,GP73,IL-37 and HBV-DNA load in patients with HBV-ACLF and their prognostic value
Xiuhong LIU ; Qingling SONG ; Miao GUO ; Cong WANG ; Daxin LEI
International Journal of Laboratory Medicine 2024;45(18):2207-2212
Objective To investigate the relationship between serum high mobility group protein B1(HMGB1),Golgi protein 73(GP73),interleukin-37(IL-37)and HBV-DNA load in patients with hepatitis B virus-associated chronic plus acute liver failure(HBV-ACLF)and the value of predicting prognosis.Methods A total of 112 HBV-ACLF patients from the 980th Hospital of PLA Joint Logistic Support Force from July 2018 to July 2023 were retrospectively analyzed,and were divided into death group(n=42)and sur-vival group(n=70)according to the clinical outcomes of HBV-CALF patients within 90 days after admis-sion.The clinical data and serum levels of HMGB1,GP73 and IL-37 of the two groups were compared,the prognotic factors of the HBV-CALF patient were analyzed,and the relationship between serum HMGB1,GP73 and IL-37 and HBV-DNA load was analyzed.The prognostic value of serum HMGB1,GP73 and IL-37 in HBV-CALF patients were evaluated.Results There were significant differences in disease stage,peritonitis,hepatic encephalopathy,pulmonary infection,HBV-DNA load and MELD score between the death group and the survival group(P<0.05).Serum levels of HMGB1,GP73 and IL-37 in death group were higher than those in survival group(P<0.05).Disease stage,peritonitis,hepatic encephalopathy,pulmonary infection,HBV-DNA load,MELD score and serum HMGB1,GP73 and IL-37 levels were all independent prognoses of HBV-ACLF patients(P<0.05).The levels of serum HMGB1,GP73 and IL-37 in HBV-ACLF patients were negatively correlated with HBV-DNA load(P<0.05).The area under the curve(AUC)values of serum HMGB1,GP73 and IL-37 in predicting the prognosis of HBV-ACLF patients were 0.781,0.790 and 0.782,re-spectively.The AUC value of the combined prediction was the largest(0.944),and the sensitivity and speci-ficity were 86.33%and 91.43%,respectively.Conclusion Serum HMGB1,GP73 and IL-37 levels are closely related to HBV-DNA load and prognosis of HBV-CALF patients,and the combined detection of these three indexes is helpful to improve prognosis prediction efficiency.
3.Perioperative application of immunoadsorption in highly sensitized kidney transplant recipients: single-center experience
Haojie HUANG ; Jie DING ; Yuting HU ; Dan SONG ; Ming ZHU ; Feng WANG ; Heng ZHENG ; Chenjie HUANG ; Qingling ZOU ; Zhangfei SHOU
Chinese Journal of Organ Transplantation 2024;45(10):702-709
Objective:To explore the clinical efficacy of immunoadsorption in highly sensitized kidney transplant (KT) candidates.Methods:From September 2019 to April 2023, the relevant clinical data were retrospectively reviewed for 26 highly sensitized KT recipients. Protein A immunoadsorption desensitization therapy was offered after KT. The effect of immunosorbent on reducing anti-human leukocyte antigen (HLA) antibodies was summarized. And operative success rate and postoperative complication incidence were calculated.Results:The mean number of treatment session was (10.76±5.53). The highest level of HLA-Ⅰ antibody mean fluorescence intensity (MFI) dropped from (17 921±4 442) to (7 333±6 434) with a decline of 59% and HLA-Ⅱ antibody MFI decreased from (21 135±5 245) to (10 989±7 627) with a decline of 48%. The differences were statistically significant (both P<0.001). All kidneys were harvested from cadavers. The complications were acute antibody mediated rejection (7 cases), perioperative pulmonary infection (3 cases) and myelosuppression (2 cases). The average follow-up period was (30.8±12.6) month. The graft survival rate was 88.5% (23/26) and the recipient survival rate 100% (26/26) . Conclusions:Immunoadsorption therapy can effectively reduce HLA antibody in highly sensitized KT candidates, thereby increasing the probability of successful KT. In terms of safety, immunosorbent therapy may boost the potential risks of infection and myelosuppression. It requires heightened attention.
4.Colon-specific controlled release of oral liposomes for enhanced chemo-immunotherapy against colorectal cancer.
Mengya NIU ; Yihan PEI ; Tiantian JIN ; Junxiu LI ; Liming BAI ; Cuixia ZHENG ; Qingling SONG ; Hongjuan ZHAO ; Yun ZHANG ; Lei WANG
Acta Pharmaceutica Sinica B 2024;14(11):4977-4993
A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8+ T cells and reactivated robust antitumor immunity.
5.Orchestrating antigen delivery and presentation efficiency in lymph node by nanoparticle shape for immune response.
Hongjuan ZHAO ; Yatong LI ; Beibei ZHAO ; Cuixia ZHENG ; Mengya NIU ; Qingling SONG ; Xinxin LIU ; Qianhua FENG ; Zhenzhong ZHANG ; Lei WANG
Acta Pharmaceutica Sinica B 2023;13(9):3892-3905
Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4+ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8+ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.
6.Hyperthermia based individual in situ recombinant vaccine enhances lymph nodes drainage for de novo antitumor immunity.
Cuixia ZHENG ; Xinxin LIU ; Yueyue KONG ; Lei ZHANG ; Qingling SONG ; Hongjuan ZHAO ; Lu HAN ; Jiannan JIAO ; Qianhua FENG ; Lei WANG
Acta Pharmaceutica Sinica B 2022;12(8):3398-3409
The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes (LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin (SV) adjuvant loaded Au nanocages (AuNCs) as cores (AuNCs/SV) and folic acid modified thermal-sensitive liposomes (FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy (PTT) induced the release of tumor-derived protein antigens (TDPAs) and the shedding of FA-TSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine (AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination.
7.Imaging " mismatch" in acute ischemic stroke
Defu ZHANG ; Weiwei SONG ; Haifei ZHENG ; Qingling ZHAI ; Jinbo CHEN
International Journal of Cerebrovascular Diseases 2020;28(9):687-692
Acute ischemic stroke has ischemic penumbra and actual infarct core, and when there is a bigger difference in the volume of the two, it is called " mismatch". It is not only manifested as a mismatch between the clinical manifestations and the infarct core, but also as a mismatch between the infarct core and the perfusion area. The advancement of neuroimaging technology enables this " mismatch" phenomenon to be manifested through different imaging methods or different sequences of the same imaging method, thereby providing more guidance for the further diagnosis and treatment process.
8.The using status quo and analysis of POCT glucose meter
Miao WANG ; Ranyun ZHOU ; Xinglong YANG ; Wenxia CHEN ; Qingling GUO ; Lijun ZENG ; Qianlin YANG ; Fan JIA ; Xin WANG ; Haihan WU ; Shiping SONG
Chinese Journal of Laboratory Medicine 2016;39(8):643-645
Objective To investigate the problems during using, standard and quality management of the POCT glucose meters in hospital, to analyze the solutions, and to provide reference data for improving the test level of POCT in hospital.Methods The amount, brand and application of portable glucose meters in the hospital were obtained by 3 rounds of surveillance from May to July in 2013.All of those glucose meters were taken part in external quality assessment of Clinical Laboratory Center of National Health and Family Planning Commission.The test results of those glucose meters were compared with that of automatic biochemical analyzer, the comparison results were then analyzed.Results The POCT glucose meters possessed 5 brands in our hospital, and the amount and type of glucose meters in some clinical departments were often changed.When 4 brands which were detected as quality control samples by ministry of health, the accuracy of detection results of 3 concentration of brand Ⅲ were substandard, the CV% of two levels were 11.9%and 10.1%respectively, the remaining 3 brands were in line with the requirements.The qualified percentages of 3 times of comparison were 85.0%, 92.0%and 97.4%.Conclusions The hospital should select the brand of portable glucose meters reasonably, correct use of glucose meters, and it is very necessary to build indoor and interstitial quality evaluation system, at the same time, suggesting the hospital to establish the POCT quality management team, to carry out the instrument comparison periodically, so to guarantee the accurate, reliable results of POCT in hospital.
9.Effect of metabolic tumor volume on the prognosis of patients with colorectal cancer
Baji BEN ; Yujuan QI ; Qingling YUAN ; Xiaoyan SONG ; Rui JI
Chongqing Medicine 2016;45(30):4246-4248
Objective To investigate the predictive value of metabolic tumor volume (MTV) in angiogenesis and hematoge‐nous metastasis of patients with colorectal cancer .Methods Totally 108 patients with colorectal cancer from January 2011 to De‐cember 2015 were enrolled into the study and divided into metastasis group (n=42) and non‐metastasis group (n=66) according to whether combining with hematogenous metastasis .All patients received 18 F‐2‐fluoro‐D‐glucose positron emission tomography/com‐puted tomography (18F‐FDG PET/CT) before operation ,then used the PET VERA software to automatically calculate MTV ac‐cording to the 40% of standard uptake value max(SUVmax ) as the threshold .The blood vessels were identified with CD34+ immu‐nohistochemical staining ,then measured the microvessel density (MVD) .The clinical pathologic data ,SUVmax ,MTV and MVD were compared between metastasis group and non‐metastasis group .The area under the receiver‐operating characteristic curve (AUC) was performed to evaluate the predictive value of MTV on hematogenous metastasis .Results SUVmax ,MTV and MVD in metastasis group were significantly higher than that in non‐metastasis group (P<0 .05) .There were significant differences in MTV and MVD among patients with different T stage (P<0 .05) .Pearson correlation analysis results showed that MTV was positively correlated with MVD (r=0 .636 ,P<0 .001) ,and there was no significant relationship between MTV and SUVmax (r= 0 .161 ,P=0 .096>0 .05) ,MVD and SUVmax (r=0 .179 ,P=0 .064>0 .05) .AUC of MTV was 0 .736 ,and the best threshold value was 15 .016 cm3 ,whose sensitivity ,specificity ,positive predictive value ,negative predictive value and Youden index were 83 .3% ,63 .6% , 59 .3% ,85 .7% and 47 .0% respectively .Conclusion Compared with SUVmax ,MTV of colorectal cancer is associated with angio‐genesis and hematogenous metastasis ,so as to predict the prognosis of colorectal cancer ,which is worthy of clinical application .
10.Effect of midazolam combined with fentanyl as adjuvant therapy on inflammatory factors and biochemical indexes in children with serious hand-foot-mouth disease with mechanical ventilation
Dongmei CHEN ; Shuang ZHANG ; Qingling TIAN ; Runchun ZHANG ; Xue FENG ; Peng SONG ; Qing ZHANG
Chinese Journal of Infectious Diseases 2015;(10):604-607
Objective To investigate the effect of midazolam combined with fentanyl as adjuvant therapy on inflammatory factors and biochemical indexes in children with serious hand-foot-mouth disease with mechanical ventilation .Methods One hundred and thirty children with serious hand-foot-mouth disease treated with mechanical ventilation were selected at Maternal and Child Health Care Hospital from January 2010 to January 2014 . The patients were divided into two groups according to the treatment regimen :58 cases treated with midazolam for sedation and analgesia as control group and 72 cases treated with midazolam combined with fentanyl as observation group . Inflammatory factors (interleukin-6 , interferon-γ ,high-sensitivity C-reactive protein and tumor necrosis factor-α) and biochemical indices (albumin ,alanine transaminase [ALT] ,aspartate transaminase [AST] ,alkaline phosphatase ,glutamate transpeptidase [γ-GT] and fasting blood glucose) before drug exposure and on withdrawal were compared between two groups .Adverse reactions were analyzed in the two groups .Continuous variables were compared using two-sample t-test , while categorical variables were compared using chi-square test . Results Interleukin-6 ,interferon-γ, high sensitive C reactive protein and tumor necrosis factor-α on withdrawal decreased significantly in both groups than those before drug exposure (all P< 0 .05) .All observation indices on drug withdrawal in observation group were significantly lower than control group (all P< 0 .05) .Levels of albumin ,ALT ,AST ,alkaline phosphatase and γ-GT were not significantly different between two time points in both groups (all P>0 .05) .However ,in observation group ,fasting blood glucose level decreased significantly on drug withdrawal compared with that before drug exposure ([5 .17 ± 0 .28] vs [10 .31 ± 1 .39] mmol/L ,t=46 .237 ,P=0 .000) ,and that was also lower than control group ([5 .17 ± 0 .28] vs [5 .85 ± 0 .34] mmol/L ,t=4 .372 ,P=0 .000) .Incidence of adverse reactions in observation group was significantly lower than control group (15 .3% vs 32 .8% ,χ2=4 .707 ,P=0 .030) . Conclusions Midazolam combined with fentanyl as adjuvant therapy is helpful to improve blood glucose , stabilize biochemical indices and reduce inflammation factor secretions in children with serious hand-foot-mouth disease with mechanical ventilation .This therapy is safe and worthy of clinical use .

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