Objective:The purpose of this study was to investigate the evaluating value of modified critical care ultrasonic examination(M-CCUE) scheme for the etiological diagnosis of shock in ICU patients.Methods:The prospective study collected relevant clinical data of various shock patients admitted to the Department of Intensive Care Medicine, Henan Provincial People's Hospital from May 2020 to July 2021, including hemodynamic、blood indicators、organ/tissue perfusion and prognostic evaluation indicators.All selected patients completed the initial M-CCUE assessment within 30 minutes, were scored according to the M-CCUE score system and related data results were analyzed.Results:Ninety-three patients were included in this study,Two of them were not completed the M-CCUE assessment due to emergency treatment immediately after entering our department, and five were excluded due to inconsistent ultrasound judgments by the two physicians. In the end, a total of 86 patients were enrolled in the group. In patients applied with M-CCUE scheme,time to preliminary diagnosis and final diagnosis were (13.02±3.15)min and (67.70±20.20)min respectively, the accuracy of diagnosis was 83.7%. Among them, distributed shock accounted for 60.4%, hypovolemic shock accounted for 25.6%, cardiogenic shock and obstructive shock accounted for 3.5%, and mixed shock accounted for 7%; MCS is (13.27±4.91), M-CCUE scheme had the high sensitivity and specificity for the diagnosis of distributed shock (sensitivity 91.2%, specificity 93.9%), hypovolemic shock (sensitivity 96.0%, specificity 96.7%), cardiogenic shock (sensitivity 85.7%, specificity 98.7%) and obstructive shock (sensitivity 60.0%, specificity 100%); MCS has a good positive correlation with APACHEⅡ score ( r=0.861, P<0.001), and has no correlation with ICU cost ( r=0.012, P=0.915). There is no significant difference in MCS between the 28d death group and the recovery group ( P=0.391). Conclusions:For shock patients admitted to ICU with unknown etiology, the initial diagnosis of the cause of the M-CCUE program takes less time, has a higher correct diagnosis rate, sensitivity and specificity, and its quantitative evaluation results can predict the patient's criticality.

Objective:To evaluate the feasibility and applicability of using phospholipid-hybridization method for preparing biomimetic microbubbles (Bio-MBs) ultrasound contrast agents.Methods:Leukocyte biomimetic microbubbles (MB leu), platelet biomimetic microbubbles (MB pla) and erythrocyte biomimetic microbubbles (MB ery) were prepared by multiple steps: film-hydration, phospholipid-hybridization, mechanical oscillation. The size and zeta potential of Bio-MBs were measured by dynamic light scattering. A laser scanning confocal microscopy experiment was performed to confirm the presence of membrane proteins on the shell of Bio-MBs. The fluorescence of FITC-labeled typical membrane protein was evaluated using a flow cytometer. Sodium dodecyl sulfate polyacrylamide gel electrophoresis was used to characterize the membrane protein. Biosafety of Bio-MBs was evaluated by CCK-8 counting kit, blood and major organs. The contrast enhancement effect and stability were observed in vitro and in vivo. An in vivo fluorescence imaging system was performed to evaluate the distribution of Bio-MBs. The application value of biomimetic microbubbles was measured by ultrasound molecular imaging by using ischemia-reperfusion rat models and acute hepatitis rat models. Results:Bio-MBs with spherical shape distributed homogenously, without obvious aggregation. The membrane proteins were successfully integrated into the shell of Bio-MBs.The diameter of three Bio-MBs was similar to that of control microbubbles (MB con) ( P>0.05), three Bio-MBs had a lower zeta potential than MB con ( P<0.05). The Bio-MBs had an appreciable performance in vitro and in vivo biosafety. The Bio-MBs retained the main proteins inherited from cell membrane. Contrast enhanced ultrasound imaging in vitro and in vivo showed that the Bio-MBs had a stable imaging ability.MB leu and MB pla have good targeted imaging effect in two disease models. Conclusions:A series of Bio-MBs ultrasound contrast agents, which have high stability, biosafety and targeted imaging efficiency, were successfully prepared by using phospholipid-hybridization method. This fabrication method for obtaining Bio-MBs can be applied to different clinical scenarios with different cell types in the future.

Objective:To explore the predictive value of thrombus markers for venous thromboembolism (VTE) in patients with malignant tumors after surgery.Methods:The clinical data of 150 patients with malignant tumors after surgery admitted to Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine in Hebei Province from July 2020 to February 2021 were retrospectively analyzed. All 150 patients followed-up for 4 weeks were treated as the observation group, including 30 cases with VTE (the thrombosis group) and 120 cases without VTE (the non-thrombosis group). Another 60 cases undergoing healthy physical examination during the same period were selected as the control group. The chemiluminescence immunoassay was used to detect thrombin-antithrombin complex (TAT), plasmin-α 2 plasmin inhibitor complex (PIC), thrombomodulin (TM), tissue-type plasminogen activator inhibitor-1 complex(tPAIC). The control group was tested once, and the observation group was tested on the 1 day before the operation and 1 day after the operation. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of thrombus markers for VTE in patients with malignant tumors after surgery. Results:The patients with lung cancer ( χ2 = 12.53, P = 0.014), ≥ 60 years old ( χ2 = 6.66, P = 0.036),body mass index>30 kg/m 2 ( χ2 = 40.53, P<0.001), tumor metastasis ( χ2 = 5.38, P = 0.031), Ⅲ-Ⅳ stage ( χ2 = 5.83, P = 0.023) had higher incidence of VTE after the operation, and the difference was statistically significant. The levels of TAT, PIC and TM in the observation group were higher than those in the control group (all P < 0.05).The levels of TAT and TM in the thrombosis group were higher than those in the non-thrombosis group before the operation, and the difference was statistically significant (all P < 0.05).The value of TM in predicting VTE was high [the best cut-off value was 10.70 TU/ml, area under the curve (AUC) was 0.786, the sensitivity was 73.30%, the specificity was 81.70%], the combination of TAT and TM could improve the predictive value (AUC was 0.796, the sensitivity was 80.00%, the specificity was 77.50%). The levels of TAT, PIC, TM and tPAIC in thrombosis group were all higher than those in the non-thrombosis group after the operation, and the difference was statistically significant (all P < 0.05). The value of TAT in predicting VTE was high (the best cut-off value was 16.50 ng/ml, AUC was 0.887, the sensitivity was 82.36%, the specificity was 71.65%), the combination of TAT, PIC, TM and tPAIC could improve the predictive value (AUC was 0.913, the sensitivity was 90.00%, the specificity was 88.60%). The level of PIC was positively correlated with TAT before and after the operation ( r = 0.66, P < 0.001; r = 0.64, P < 0.001). Conclusions:TM can be used as a sensitive indicator in the early prediction of VTE for the patients with malignant tumors and it aims at the prevention; TAT can be used as a specific indicator in predicting the development of VTE and it aims at the intervention in time. The combined detection of TAT, PIC, TM and tPAIC can improve the predictive value of VTE. At the same time, PIC can be used to evaluate the risk of bleeding.

Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; COVID-19 Vaccines ; Humans ; Immunization Schedule ; SARS-CoV-2 ; Vaccines, Inactivated

Objective:To assess the value of point of care ultrasound on cardiac output (CO) and volume responsiveness in patients with septic shock.Methods:A prospective investigation study was conducted. Twenty-four mechanical ventilation patients with septic shock who needed pulse-indicated continuous cardiac output (PiCCO) monitoring in the department of critical care medicine of Zhengzhou University People's Hospital, Henan Provincial People's Hospital from November 25, 2020 to April 30, 2021 were selected as the subjects, the patient's basic information and laboratory test results were recorded. PiCCO was used as standard to monitor CO and stroke volume variability (SVV) at 0, 2, 6, 12, 24 and 48 hours. At the same time, point of care transthoracic echocardiography (TTE) was used to measure velocity time integral (VTI) and inferior vena cava diameter (dIVC), the CO, VTI variation rate (△VTI) and dIVC variation rate (△dIVC) were calculated. Then, using the value monitored by PiCCO as the standard, the consistency and correlation analysis were carried out between point of care ultrasound with PiCCO.Results:Twenty-two out of 24 patients obtained satisfactory ultrasound Doppler images, the heart rate (HR), mean arterial pressure (MAP) and body temperature of the enrolled patients were consistent with the pathophysiological characteristics of septic shock. With the extension of treatment time, HR and CO both gradually decreased, and MAP gradually increased, reaching a peak or trough at 48 hours after admission. The difference were statistically significant compared with the time of admission [HR (bpm): 90.36±15.35 vs. 116.82±19.82, MAP (mmHg, 1 mmHg = 0.133 kPa): 87.82±11.06 vs. 58.82±9.85, CO (L/min): 4.80±0.56 vs. 6.78±1.31, all P < 0.05]. The CO obtained by PiCCO and point of care ultrasound had good agreement [5.36 (4.78, 6.33) L/min and 5.21 (4.88, 6.35) L/min, respectively], the average difference value at each time point was (-0.02±0.69) L/min, the 95% agreement limit range was -1.35-1.34, and there was a high degree of correlation ( rs = 0.800, P < 0.001); The SVV by PiCCO and the △dIVC by point of care ultrasound were in good agreement [18.00% (14.00%, 24.00%) and 21.00% (14.00%, 25.75%), respectively], the average difference value at the time point was (-3.16±6.89)%, the 95% agreement limit range was -16.89-10.54, and there was a moderate correlation ( rs = 0.702, P < 0.001); The SVV by PiCCO and the △VTI by point of care ultrasound were in good agreement [18.00% (14.00%, 24.00%) and 16.00% (11.25%, 20.75%), respectively], the average difference value at each time point was (13.03±14.75)%, and the 95% agreement limit range was 1.72-27.78, and there was a high correlation ( rs = 0.918, P < 0.001). Conclusion:Point of care ultrasound can accurately assess CO and volume responsiveness of patients with septic shock, and the △VTI is better than the △dIVC in assessing volume responsiveness.

Objective:To evaluate the effects of dexmedetomidine on the content of glutamate and expression of NR1 in hippocampus of mice with endotoxemia and the role of cholinergic anti-inflammatory pathway.Methods:Eighty clean-grade male C57BL/6 mice, aged 8 weeks, weighing 24-28 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), endotoxemia group (group LPS), dexmedetomidine group (group DEX) and alpha-bungarotoxin (α-BGT) group.Lipopolysaccharide 20 mg/kg was intraperitoneally injected to establish the model of endotoxemia in LPS, DEX and α-BGT groups. Dexmedetomidine 40 μg/kg was intraperitoneally at 15 min before establishing the model in DEX and α-BGT groups.In group α-BGT, alpha-7 nicotinic acetylcholine receptors specific agonist α-BGT 1 μg/kg was intraperitoneally injected at 15 min before injecting dexmedetomidine.Ten mice taken in each group were selected to collect the blood samples from the eyeball and then sacrificed, and hippocampi were isolated.Enzyme-linked immunosorbent assay was used to measure the concentration of serum S100β protein and NSE, and high-performance liquid chromatography was used to determine the content of glutamate in hippocampus.Ten mice in each group were sacrificed at 6 h after establishing the model to detect the expression of NR1 in hippocampus by immumofluorescence method. Results:Compared with group C, the concentrations of serum S100β protein and NSE concentrations and hippocampal glutamate content were significantly increased, and NR1 expression was up-regulated in LPS, DEX and α-BGT groups ( P<0.01). Compared with group LPS, the concentrations of serum S100β protein and NSE concentrations and hippocampal glutamate content were significantly decreased, and NR1 expression was down-regulated in DEX and α-BGT groups ( P<0.01). Compared with group DEX, the concentrations of serum S100β protein and NSE concentrations and hippocampal glutamate content were significantly increased, and NR1 expression was up-regulated in group α-BGT ( P<0.01). Conclusion:The mechanism by which dexmedetomidine alleviates cerebral injury is associated with activating cholinergic anti-inflammatory pathway, decreasing glutamate content and down-regulating NR1 expression in mice with endotoxemia.

To evaluate the impact of intrahepatic cholestasis on liver stiffness measurement ( LSM ) of two‐dimensional shear wave elastography ( 2D‐SWE ) in patients with chronic hepatitis B . Methods Between June 2011 and December 2016 , total of 1 188 patients with chronic hepatitis B infection were enrolled to collect clinical ,2D‐SWE ,biochemical variables and histological ( M ET AVIR scoring system ) datas . LSM was compared between normal total bilirubin group ( TB ＜ 23 .9 μmol/L ) versus abnormal TB group( ≥23 .9 μmol/L ) . Correlation of TB with LSM s was assessed . Results Nine hundred and seventy‐three patients with effective LSM in the study were analyzed . Within the same fibrosis stage ( F1‐F4) ,LSM showed significantly higher value in abnormal TB group than those of normal TB group ( r＝0 .328 ,0 .247 ,0 .495 ,0 .435 ,all P ＜ 0 .001 ) . Increased LSM for abnormal TB group was generally found within different subset of patients [ fibrosis stage ≤ F2 ,AL T ≥ 2 × upper limit of normal ( ULN ) ;fibrosis stage≤ F2 ,M ET AVIR activity grade ≤ A1 or ≥ A2 ] ,with r ＝ 0 .266 ,0 .210 ,0 .243 ( all P ＜0 .001) ,respectively .Increased LSM for abnormal TB group was also found within different subset of patients [ fibrosis stage≥F3 ,AL T＜2× ULN ,≥2×ULN ; fibrosis stage≥F3 ,M ET AVIR activity grade≥A2 ,with r ＝ 0 .671 ,0 .200 ,0 .468 ( all P ＜ 0 .05 ) ] . Conclusions Hepatogenous jaundice induced to intrahepatic cholestasis shows slight positive correlation with LSM s in patients with chronic hepatitis B .

Objective To understand the detection rate of hashimoto's thyroiditis (HT) and the occurrence of abnormal thyroid function in medical examination population in Huanghua City,Hebei Province.Methods Using the retrospective analysis method,the thyroid examination data of residents of Huanghua City who were examined in the Cangzhou Hospital of Traditional Chinese and Western Medicine in Hebei Province from 2014 to 2016 were collected,the detection rate of HT and the occurrence of abnormal thyroid function were analyzed.Results A total of 4 413 people were examined,aged (45.76 ± 10.13) years old;including 2 099 males and 2 314 females.The HT detection rate of the medical examination population in Huanghua City was 6.55％ (289/4 413),and there was a trend of increasing year by year (x2trend =7.126,P ＜ 0.05).The difference in HT detection rates between different genders (male:2.86％,famale:9.90％) was statistically significant (x2 =89.077,P ＜ 0.05);there was a statistically significant difference in the HT detection rates among women of different age groups (x2 =18.541,P ＜ 0.05),and there was no significant difference in the detection rates of HT among men of different age groups (x2 =8.424,P ＞ 0.05).The incidence of abnormal thyroid function in HT patients was 25.61％ (74/289),of which the highest detection rate was 34.74％ (33/95) in the 40-＜ 50 years old group;the detection rates of HT with hyperthyroidism,hypothyroidism and subclinical hypothyroidism were 3.11％ (9/289),6.57％ (19/289) and 15.92％ (46/289),respectively.The detection rate of HT with subclinical hypothyroidism was higher.Conclusions The HT detection rate of the population in Huanghua City has increased year by year,and some HT patients are associated with abnormal thyroid function,and their detection rate of HT with subclinical hypothyroidism is the highest.Early diagnosis of HT should be strengthened,and appropriate prevention and treatment measures should be taken in time to reduce the occurrence of HT with abnormal thyroid function.

Objective To evaluate the clinical application value of intra-biliary contrast-enhanced ultrasound (IB-CEUS) in the evaluation of degree of biliary obstruction.Methods Clinical data of 105 patients with biliary obstructive disease who were diagnosed and treated in the Third Affiliated Hospital of Sun Yat-sen University from January 2008 to December 2012 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. There were74 males and 31 females with the age ranging from 30 to 88 years old and the median age of 55 years old. Conventional ultrasound (CUS) and IB-CEUS were used to detect the biliary obstructive lesions in 105 patients. X-ray or CT cholangiography was used as the gold standard for diagnosis. The diagnostic efficacy of two methods was compared. The differences between these two methods and the gold standard in diagnosing the degree of biliary obstruction were evaluated by McNemar test. The consistency of the Results was assessed by Kappa consistency.Results The diagnostic sensitivity and negative predictive value of two methods were 100％ in diagnosing the complete obstruction of primary and second grade intrahepatic bile ducts. The specificity, positive predictive value and accuracy of IB-CEUS in diagnosing the complete obstruction of primary grade intrahepatic bile ducts was respectively 95.8％, 91.9％ and 97.1％, higher than 57.7％, 53.1％ and 71.4％ of CUS. The specificity, positive predictive value and accuracy of IB-CEUS in diagnosing the complete obstruction of second grade intrahepatic bile ducts was respectively 97.3％, 83.3％ and 97.6％, higher than 58.6％, 24.6％ and 63.5％ of CUS. Significant difference was observed in the diagnosis between CUS and gold standard (χ2=28.033, 46.000; P<0.05). CUS was fair or poor for the consistency of Results in diagnosing the complete biliary obstruction of primary and second grade intrahepatic bile ducts (k=0.470, 0.252), while no significant difference was observed between IB-CEUS and gold standard (P=0.250) and the consistency of Results was good (k=0.936, 0.896).Conclusions IB-CEUS can accurately evaluate the degree of intrahepatic biliary obstruction. The efficacy of IB-CEUS is better than that of CUS, and it has a good diagnostic consistency with the gold standard.

Objective To prepare PET molecular probe folate-NOTA-Al18F(18F-FNA) and to explore its feasibility as an imaging agent in folate receptor positive KB tumor.Methods 18F-FNA was prepared by the method of aluminum fluoride coordination labeling, and the effect of phase transfer catalyst K2.2.2 on the labeling yield was evaluated.Biological distribution was carried out at 10, 30 and 90 min after injection of 3.7 MBq 18F-FNA in nude mice (n=20) xenografted with KB tumor, and the radioactive uptake (%ID/g) and T/NT ratios were then calculated in different organs or tissues.MicroPET imaging was performed at 40 min after injection of 18F-FNA (3.7 MBq).Results The labeling yield of 18F-FNA increased with the presence of K2.2.2.The radiochemical yield was above 98%.The radiochemical purity was above 99%, and still above 98% after maintained in PBS and FBS at 37 ℃ for 4 h.The biodistribution showed that the blood clearance of the probe was slow, and the uptakes in kidneys and tumor which overexpressed folate receptor were significantly high ((5.12±0.58) %ID/g and (1.37±0.20) %ID/g).The high radioactive uptake was observed in KB xenografted mice using microPET imaging.Conclusions The labeling yield of 18F-FNA could increase with the presence of K2.2.2.Furthermore, the encouraging biological distribution and microPET imaging results indicate that 18F-FNA may be a candidate for PET imaging in targeting folate receptor.