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In recent years, a large number of studies have found that Parkinson's disease (PD) patients often complicate with osteoporotic fracture, which may be related to decreased dopamine transmitters, PD risk gene mutations, mitochondrial dysfunction, vitamin D reduction, anti-PD drug use, autonomic nervous dysfunction and intestinal microflora disorders. Therefore, this paper reviews the current research progress on the pathogenesis of osteoporotic fracture in PD patients to provide theoretical basis for co-morbid treatment of PD and osteoporotic fracture.
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In recent years, it has been common for heart disease patients to undergo urological surgery.The requirements for specialized doctors to accurately assess the risk of perioperative heart disease thrombosis are also increasing. In order to conduct multi-disciplinary disease analysis and discussion in a more standardized profile and promote clinical work progress in a safer manner, this article provides a systematic review and summary of the basic characteristics of antithrombotic drugs, the bleeding risks of urological surgery, the risk identification standards for arteriovenous thrombosis, as well as the withdrawal conditions, bridging selection, and restart treatment of perioperative antithrombotic drugs, based on the constantly updated clinical researches and guideline consensuses in recent years.
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Objective:To introduce a reliable and easy method of philtrum crest and philtrum repairing in secondary repair of cleft lip.Methods:Lift the upper lip flap after removing the scar on upper lip. Then the superficial orbicularis oris muscle was carefully separated, which formed the abnormal muscular eminence in the affected side after the first cleft lip repair. The pedicle of the orbicularis oris muscle the reconstructing philtrum crest. The lingual orbicularis oris muscle flap was lifted and curled from outside. The superficialorbicularis oris muscle was cut in philtrum longitudinally and turned outward. The two evertedorbicularisoris muscle flaps were sutured on both sides and fixed them on the reconstructing philtrum crest. The exposed deep orbicularis oris muscle in philtrum was sutured with the upper dermis, which formed the prominentphiltrum crest and deeper philtrum.Results:We reviewed the hospital records of patients from July 2008 to November 2021. In total, 201 patients were included in this study. All of these patients underwent the reconstruction of philtrum crest and philtrum with orbicularis oris muscle intertangling and philtrum plasty in secondary cleft lip repairing. During the treatment, the patients had no complications such as infection, hematoma and flap necrosis.198 patients were observed from 1 months to 36 months (7.8 months on average). All of them improved in different degrees in early postoperative period. Most reconstructed philtrum crest was raised and basically symmetrical with the contralateral side in shape. The philtrum was clear and the scar was not obvious. The reconstructed philtrum crest would decrease with time. 91.7% (90/98) patients were satisfied with the postoperative effects after three months.Conclusions:The method of reconstruction of philtrum crest and philtrum with orbicularis oris muscle intertangling and philtrum plasty in secondary cleft lip repairing is safe and effective. The long term postoperative effect is stable with high satisfaction as well. As a result, this method can be used as the philtrum crest and philtrum correction scheme for secondary cleft lip repairing.
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【Objective】 To compare the outcomes of robot-assisted laparoscopic transperitoneal and retroperitoneal operation for huge (>6 cm) adrenal tumors. 【Methods】 The clinical data of 45 patients with huge adrenal tumors who underwent robotic surgery during Jan.2017 and Dec.2021 were retrospectively analyzed, including 28 cases via the transperitoneal approach and 17 cases via the retroperitoneal approach. 【Results】 No patients were converted to open operations. There were no significant differences in postoperative drainage time (2.24±0.44 vs. 2.36±0.49) d, operation time (130.88±5.96 vs. 136.61±8.39) min, blood loss (189.41±13.91 vs. 192.5±12.36) mL and postoperative hospital stay (7.06±0.56 vs. 7.46±0.69) d between the retroperitoneal and transperitoneal approaches. Retroperitoneal approach was better than transperitoneal approach in early postoperative feeding [(38.82±6.75 vs. 74.14±6.57) h, P<0.01] . 【Conclusion】 Robotic surgery is safe and effective in the treatment of large adrenal tumors. The choice of surgical approach should be based on patients’ condition, tumor volume and location.
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TAR DNA/RNA-binding domain protein 43 (TDP-43) has become one of the pathogenic factors of many neurodegenerative diseases, such as Alzheimer's disease (AD). Clearance of abnormal accumulation of TDP-43 might be the potential treatment target in AD patients. Ubiquitin-proteasome system (UPS) is one of the main ways of protein clearance. UPS dysfunction plays an important role in the pathogenesis and progression of AD. This review focuses on the roles of TDP-43 and UPS in the pathogenesis of AD, as well as the research progress of UPS mediated clearance TDP-43 in the treatment of AD.
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Parkinson's disease (PD) is a disease characterized by abnormal aggregation of α-synuclein, and its motor symptoms and non-motor symptoms have a serious impact on patients' daily life. Because its pathogenesis is not completely clear, drugs that can stop or slow down the progression of PD lack in clinical practice. At present, scholars believe that the disorder of intestinal microorganisms and their metabolites is one of the driving factors for PD. In this paper, we review the positive effect of butyric acid, an important metabolic substance of intestinal microorganisms, on PD, providing new idea for drug research.
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Objective:To study the characteristics of breath sound spectroscopy in chronic obstructive pulmonary disease(COPD) patients with different lung function grades, to preliminarily determine the characteristic parameters and indicators of breath sound spectrograms with different lung function grades of COPD, and to explore the visualization and measurability of the differences in respiratory auscultation in patients with different lung function grades.Methods:Patients diagnosed and treated in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Chongming Branch from October 2018 to December 2020 were selected. Fifty-two patients with COPD (22 patients with moderate to moderate obstructive ventilation dysfunction (mild to moderate group), 30 patients with severe obstructive ventilation dysfunction (severe group)) and 36 normal controls (control group) were selected. The respiratory sounds were sampled with an electronic stethoscope and transmitted to the audit audio software to calculate the relevant data of respiratory sound pressure level (SPL) and the ratio to minute ventilation (VE) of samples with different lung function grades. A retrospective case-control study was used. The data with normal distribution were analyzed by one-way ANOVA, and the pairwise comparison was performed by SNK- q test. Results:The breathing audio frequency of mild-moderate, severe COPD patients and the control group has a sound pressure difference of (-0.5±2.2) dB and (-1.6±6.1) dB, (0.7±4.0) dB, and there was significant difference between each group ( F=2.64, P=0.038). The sound pressure level per minute ventilation (SPL 50-200/VE) of respiratory sound inspiratory phase in COPD patients with mild to moderate and severe obstructive ventilation dysfunction and the control group were (5.7±1.8) dB/L, (6.1±2.3) dB/L and (5.4±0.9) dB/L, respectively. The expiratory SPL 50-200/VE were (5.8±1.7), (6.3±2.2) and (5.3±1.2) respectively. There was significant difference among the three groups ( Finhalation=3.26, P=0.048; Frespiration=2.44, P=0.045). ROC curve results showed that SPL 50-200/VE in the inspiratory phase, SPL 50-200/VE in the expiratory phase, and sound pressure difference to assess different grades of obstructive ventilatory dysfunction had diagnostic value (AUC values were 0.697, 0.725 and 0.686, respectively; and P values were 0.015, 0.005 and 0.022, respectively). In some patients with COPD, abnormally high energy levels may appear in the time-frequency diagram of breath sounds. Conclusion:There are significant differences in respiratory audio spectrum analysis between patients with different degrees of obstructive ventilation dysfunction and those with normal ventilation function, which can provide a basis for auxiliary judgment of obstructive ventilation dysfunction.
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ObjectiveTo explore the relationship among loneliness， Internet addiction and online deviant behavior of students in police colleges， and to discuss the related mechanism. MethodsIn March 2020， 766 students from a police college in Sichuan were selected by cluster sampling method， and assessed using University of California at Los Angeles-Loneliness Scale （UCLA-LS）， Diagnostic Scale for Internet Addiction Disorder （DSFIAD） and College Students' Online Deviant Behavior Questionnaire， then SPSS 20.0 software was used for statistical， and Mplus 8.0 software was used to test the mediating and moderating effects. Results①The Online Deviant Behavior Questionnaire score of male students in police college was higher than that of female students （t=7.560， P<0.01）. ②UCLA-LS score was positively correlated with DSFIAD score （r=0.406， P<0.01）， and Online Deviant Behavior Questionnaire score was positively correlated with UCLA-LS and DSFIAD scores （r=0.279， 0.592， P<0.01）. ③Loneliness could positively predict online deviant behavior （β=0.279， t=9.041， P<0.01）. ④Internet addiction played a full mediating role between loneliness and online deviant behavior， with a mediating effect size of 0.233 （95% CI： 0.190~0.279， P<0.01）， accounting for 83.51% of the total effect. ⑤Gender played a regulatory role in the second half （Internet addiction → online deviant behavior） of the intermediary path of "loneliness → Internet addiction → online deviant behavior" （β=-0.192， t=-4.461， P<0.01）. ConclusionThe loneliness of police college students cause a direct impact on the online deviant behavior， and also pose an indirect impact on online deviant behavior through Internet addiction. Furthermore， loneliness has a moderated mediation effect on online deviant behavior， and is only significant in the male students.
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@#Objective To investigate the mechanism of CirCDC14A silencing to protect astrocytes from oxygen-glucose deprivation/glyco-reoxygenation (OGD/R)-induced injury by regulating the miR-153-3p/JAK1 axis.Methods Cerebral cortical astrocytes of neonatal rats were cultured in vitro,and the cell viability was detected by CCK-8 method;annexin V-FITC/PI staining was used to detect cell apoptosis.Western blot method was used to detect the protein expression levels of p53,Bax and Bcl-2 in each group,and the relationship between CirCDC14A and miR-153- 3p,miR-153-3p and JAK1 was analyzed by dual-luciferase reporter gene assay.Results The cell viability increased with time; the cell viability of pcDNA3.0 CirCDC14A+si JAK1 group at 48 h and 72 h was lower than that of si-NC group,OGD/R group and OGD/R+Si+Con mimcs group (P<0.05);compared with si-NC group,the apoptosis of OGD/R group,OGD/R+Si+Con mimcs group,pcDNA3.0-CirCDC14A+si JAK1+miR-153-3p mimcs group increased significantly,and pcDNA3.0-CirCDC14A+si JAK1+miR-153-3p mimcs group had higher apoptosis than OGD/R+Si+Con mimcs group (P<0.05);Western blot results showed that:pcDNA3.0-CirCDC14A+si JAK1+miR,the protein expression levels of p53,Bax and Bcl-2 in the miR-153-3p mimcs group were lower than those in the OGD/R group,OGD/R+Si+Con mimcs group and si-NC group (P<0.05).Reduced the luciferase activity of CirCDC14A WT and JAK1-WT (P<0.05); the level of miR-153-3p in the pcDNA3.0-CirCDC14A+si JAK1+miR-153-3p mimcs group was lower than that in the other three groups (P<0.05). The JAK1 protein level was higher than the other three groups (P<0.05).Conclusion CirCDC14A gene silencing may inhibit OGD/R-induced apoptosis of rat astrocytes by regulating the miR-153-3p/JAK1 axis,resulting in decreased cell viability and protein expression levels of p53,Bax and Bcl-2.
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Rheumatoid arthritis (RA) is a chronic autoimmune disease with a high disability rate and unknown etiology.Early diagnosis and early treatment are essential to prevent the further development of the disease.In reeent years, metabolomics teeh- niques have been widely used in various fields of life sciences because of its wholism, dynamics, high sensitivity and high throughput.This artiele reviews the progress of metabolomics technology in various aspects of RA investigations sueh as early diagnosis, disease classification as well as drug efficacy prediction in order to provide new ideas for clinical diagnosis and treatment of RA from the metabolic perspective.
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Objective To observe the effect of electroacupuncture on the formation of glial scars in the cerebral cortex of rats with focal cerebral ischemia/reperfusion( I /R) . Methods The focal cerebral ischemia/reperfusion model was established by thread method, and "Baihui" ( GV 20) and left "Siguan" (Hegu LI 4/Taichong LR 3) were selected as acupoints points. Seventy-eight male SD rats were randomly divided into sham group ( sham) , focal cerebral ischemia/ reperfusion ( I/R) , focal cerebral ischemia/reperfusion + electroacupuncture group ( I/R + EA ) . Seven days after reperfusion, modified neurological severity score ( mNSS) was used to evaluate neurological deficit, HE staining was used to observe the degree of ischemic cerebral cortex. Immunofluorescencte was used to observe glial fibrillary acidic protein (GFAP) /neurocan, GFAP/phosphacan positive cells in the ischemic cerebral cortex. The average immunofluorescent intensity of GFAP, neurocan and phosphacan, and the levels of GFAP, neurocan and phosphacan mRNA in the ischemic cerebral cortex were analyzed by Real-time PCR, respectively. Results Compared with the I/R group, mNSS score in I/R+EA group decreased significantly (P<0. 01) , and the degree of brain tissue damage reduced obviously. There were very few GFAP+/neurocan+ cells and GFAP+/phosphacan+ cells in the sham group. The astrocytes in I/R group were Irypertroplry, increasing and thickened protrusions, more GFAP+/neurocan+ cells and GFAP+/phosphacan+ cells weredectected as well. While the count of GFAPVneurocan+ cells and GFAP+/phosphacan+ cells in I/R + EA group were significantly lower than those in I /R group. In addition, the average immunofluorescence intensity of GFAP, neurocan and phosphacan in I/R+EA group, and mRNA content of above mentioned indicators were significantly lower than those in I/R group ( P < 0. 05 ) . Conclusion Electroacupuncture promotes the recovery of neurological function in rats with focal cerebral I /R and reduce brain tissue damage, which may be related to the inhibition of glial scar fonnation in cerebral cortex.
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Objective:To investigate the neuroprotective effect of Danggui Shaoyaosan （DSS） in a rat model of amyloid-<italic>β</italic>-peptide<sub>1-42</sub> （A<italic>β</italic><sub>1-42</sub>）-induced Alzheimer's disease （AD） as well as its regulatory effect on NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase-1） signaling pathway. Method:The AD animal model was established via intracerebral injection of A<italic>β</italic><sub>1-42</sub> and treated with different concentrations of DSS after the division of rats into the sham operation group， model group， as well as the high-， medium-， and low-dose DSS groups. Morris water maze test was conducted to determine the learning and memory abilities of rats. The morphology and function of neurons were detected by hematoxylin-eosin （HE） staining and Golgi staining， followed by immunofluorescence co-localization of NLRP3 inflammasome activation. The mRNA expression levels of interleukin （IL）-1<italic>β</italic> and IL-18 were measured by Real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of NLRP3， Caspase-1， and IL-1<italic>β </italic>were assayed by Western blot. Result:Compared with the sham operation group， the model group exhibited significantly decreased learning and memory abilities （<italic>P</italic><0.01）， impaired neuronal morphology and function， up-regulated IL-1<italic>β</italic> and IL-18 mRNA expression， enhanced NLRP3 inflammasome activation， and elevated NLRP3， Caspase-1， and IL-1<italic>β</italic> protein expression （<italic>P</italic><0.01）. Compared with the model group， DSS at both medium and high doses remarkably improved the learning and memory abilities of AD rats （<italic>P</italic><0.05， <italic>P</italic><0.01）， restored neuronal morphology and function， down-regulated the mRNA expression levels of inflammatory factors IL-1<italic>β</italic> and IL-18， reduced the activation of NLRP3 inflammasomes， and lowered the protein expression levels of NLRP3， Caspase-1， and IL-1<italic>β</italic> （<italic>P</italic><0.01）. Conclusion:DSS inhibits inflammasome activation and neuroinflammatory response possibly by regulating the NLRP3/Caspase-1 signaling pathway， thus exerting the neuroprotective effect.
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OBJECTIVE@#To explore the feasibility of using the bidirectional local distance based medical similarity index (MSI) to evaluate automatic segmentation on medical images.@*METHODS@#Taking the intermediate risk clinical target volume for nasopharyngeal carcinoma manually segmented by an experience radiation oncologist as region of interest, using Atlas-based and deep-learning-based methods to obtain automatic segmentation respectively, and calculated multiple MSI and Dice similarity coefficient (DSC) between manual segmentation and automatic segmentation. Then the difference between MSI and DSC was comparatively analyzed.@*RESULTS@#DSC values for Atlas-based and deep-learning-based automatic segmentation were 0.73 and 0.84 respectively. MSI values for them varied between 0.29~0.78 and 0.44~0.91 under different inside-outside-level.@*CONCLUSIONS@#It is feasible to use MSI to evaluate the results of automatic segmentation. By setting the penalty coefficient, it can reflect phenomena such as under-delineation and over-delineation, and improve the sensitivity of medical image contour similarity evaluation.
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Estudios de Factibilidad , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
Objective:To explore the relevant factors for remote diffusion-weighted imaging lesions (R-DWILs) in patients with spontaneous intracerebral hemorrhage.Methods:Two hundred and three patients with spontaneous intracerebral hemorrhage, admitted to our hospital from January 2018 to December 2019, were enrolled. According to the presence of R-DWILs, these patients were divided into positive group ( n=39) and negative group ( n=164). The basic information of R-DWILs in the positive group was analyzed. The basic demographic and clinical data and laboratory examination results were collected and compared between the two groups. Subsequently, the items with P<0.1 were included in the multivariate Logistic regression analysis to identify the independent influencing factors for R-DWILs. Results:A total of 55 R-DWILs were detected in 39 patients (19.2%) with spontaneous intracerebral hemorrhage, including 45 in the cortical and subcortical area (81.8%), 8 in the basal ganglia area (14.5%), one in the brainstem area (1.8%), and one in the cerebellum area (1.8%). The diameter of these lesions ranged from 2-20 mm, which were round or oval, flaky, irregular and so on. Forty-two R-DWILs (76.4%) were in the contralateral hemisphere, and the number of R-DWILs was 1-3 in these patients. Systolic blood pressure, diastolic blood pressure, white blood cell count (WBC), neutrophil count, neutrophil to lymphocyte ratio (NLR), fasting blood glucose level in the positive group were significantly higher than those in the negative group ( P<0.05). Logistic regression analysis showed that fasting blood glucose level ( OR=1.632, 95%CI: 1.213-2.072, P=0.015), neutrophil count ( OR=1.037 , 95%CI: 1.019-1.581, P=0.042), and NLR ( OR=2.151 , 95%CI: 1.397-2.733, P=0.003) were independent influencing factors for R-DWILs. Conclusions:R-DWILs are common in patients with spontaneous intracerebral hemorrhage, the lesions mainly occur in the cortical and subcortical area, and it is more common in the contralateral hemisphere. Patients with high fasting blood glucose, neutrophil count, and NLR are trended to have R-DWILs.
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Objective:To investigate the effects of critical care chest ultrasonic examination(CCUE)on different fluid management phases among septic shock infants in pediatric intensive care unit(PICU).Methods:Twenty-two infants who were hospitalized in PICU during January 2017 to December 2018 and diagnosed as septic shock were included in this study.These infants received shock and infection management as well as mechanical ventilation according to the septic shock management guidelines.CCUE was applied as needed to monitor the hemodynamic status for titrated adjustment in fluid and vasoactive drug management and its impacts were evaluated.Results:The change frequencies of treatment regimen according to CCUE evaluation were different among different phases( P<0.001). Compared with the other 3 phases, the number of adjustment made to fluid management scheme caused by CCUE during the first phase was the largest(75.0%, P<0.001), and that during the fourth phase was the smallest(2.3%, P<0.01). The frequency of change during the second phase(30.5%) and the third phase(23.5%) showed no difference( P=0.210). During the first phase, compared with the group with intravenous infusion speed<10 mL/(kg·h), the group with faster intravenous infusion speed had lower LUS score and more proportion of LVEF and RVEF above 50%( P<0.05). During the second phase and the third phase, compared with group receiving slower intravenous infusion, group with faster intravenous infusion had more LVEF>50%( P<0.05). Conclusion:Application of CCUE to monitor dynamic hemodynamic of infants with septic shock in PICU has different effects on fluid management scheme adjustment at different phase.CCUE evaluation during the early 3 phases, especially during the first phase has greater influence on fluid management strategy.Rapid infusion under CCUE monitoring is often limited by cardiac ejection fraction, LUS, and mainly LVEF, especially during the first phase.Multiple ultrasonic indicators should be combined with clinical data for full evaluation.
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Objective To investigate the mechanism of TREM2 modulating the polarization of M2 microglia treated by oxygen-glucose deprivation/reoxygenation (OGD/R). Methods Mouse N9 microglial cells were cultured in vitro. N9 cells were transfected with lenti virus for TREM-2-overexpression (LV-TREM2), and LV-scramble acted as control group. OGD/R model was established. The OGD/R cells were randomly divided into OGD/R, OGD/R+LV-scramble and OGD/R+LV-TREM2 groups. Real-time PCR was used to detect the expression of TREM2 mRNA in OGD/R N9 cells within 72 hours after re-oxygenation. Immunofluorescence was applied to observe transfection of lentivirus LV-scramble and LV-TREM2 for normal N9 microglia, and Real-time PCR and Western blotting were used to verify the efficiency of lentivirus transfection. The mRNA and protein contents of Ml microglial markers tumor necrosis factor-a (TNF-α), interleukin-lβ (IL-lβ) and inducible nitric oxide synthase (iNOS), M2 microglial markers arginase-1 (Arg-1) and interleukin-10 (IL-10) were detected by Real-time PCR and ELISA. The expressions of phosphorylated-phosphatidylinositol 3-kinases (p-PI3K), PI3K, phosphorylated protein kinase B (p-Akt), Akt, phosphorylated inhibitor of nuclear factor-κB ( NF-κB)α (p-lκBα) and IκBα protein were detected by Western blotting. The distribution of NF-κB P65 (NF-κB P65) protein in N9 cells was analyzed by immunofluorescence method. Results TREM2 mRNA content in the OGD/R group cells increased significantly within 72 hours after re-oxygenation, and peaked at hour 24 and hour 48. Lenti virus LV- TREM2 effectively promoted the expression of TREM2 mRNA and protein of N9 cells in OGD/R model (P<0.001, P<0.01). Compared with the OGD/R group, the mRNA and protein content of TNF-α, IL-lβ and iNOS decreased significantly, while Arg-1 and IL-10 in OGD/R+LV-TREM2 group increased significantly(P<0.05). Besides, the ratios of P-PI3K/PI3K and p-Akt/Akt increased obviously (P<0.05), the ratio of p-IκBα/IκBα decreased significantly in OGD/ R+ LV-TREM2 group (P<0.001), and the nuclear translocation of NF-κB P65 protein was obviously weakened. Conclusion TREM-2 overexpression exerts anti-inflammatory effect by modulating the polarization of microglia from Ml to M2 type, which is associated with PI3K/Akt and NF-κB signaling pathways regulated by TREM2 in N9 microglia with OGD/R model.
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OBJECTIVE: To discuss the technical requirements of scored tablets combining with the current situation of clinical use of scored tablets and the domestic and national technical requirements. METHODS: The FDA guidance on tablet scoring was introduced in detail, on this basis, the general considerations on the technical requirements of generic scored tablets were put forward. RESULTS: AND CONCLUSION: It was suggested that the evaluation criteria should be established on the basis of taking a full consideration on product characteristics in the process of research and development, scored tablets should be developed in accordance with clinical needs, and specification description should be standardized for clarifying the clinical use of the scored tablets.
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This paper showed bioprinted HepG2 tumor tissues used for studying the sonodynamic anticancer activity of chlorine e6 (Ce6). HepG2 cells were printed by using alginate/gelatin/hydroxyethyl cellulose composite biomaterial as bio ink and cell viability was detected with Live-Dead assay and MTT proliferation. The ultrasonic intensities of self-built micro ultrasonic device under different powers were estimated by using the temperature change caused by the conversion of acoustic energy to heat energy. Ce6 of 14.3 and 28.6 μg·mL-1 were acted on two-dimensional cultured and three-dimensional printed HepG2 cells, and the antitumor activity of Ce6 was detected by MTT method with ultrasound intensity of 0.15 W·cm2 for 60 s. The results showed that the activities of bioprinted HepG2 cells were as high as 95%, and tumor microspheres were formed after 7 days of culture. The ultrasound intensity was lower than 3 W·cm2, which belonged to low ultrasound intensity and had no damage to normal hepatocyte LO2 cells. By comparing the antitumor activity of Ce6 on 2D cultured and printed HepG2 cells, it was found that the anticancer activity of Ce6 on bioprinted HepG2 cells was 63.4% lower than that on 2D culture cells, indicating the acoustic drug resistance of three-dimensional tumor model. Bioprinted tumor tissues show the potential in the application of in vitro activity evaluation models for sonodynamic therapy.
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Objective:To investigate the effects of critical care chest ultrasonic examination (CCUE) by intensive care physician on fluid management among septic shock patients in pediatric intensive care unit (PICU).Methods:Forty children from PICU who were diagnosed as septic shock in Shenzhen Bao′an Maternal and Child Health Hospital were included in this study.Twenty-two of them who were hospitalized in PICU during January 2017 to December 2018, under the care of 4 PICU physicians who had certificates of the Chinese Critical Ultrasound Study Group(CCUSG) were defined as CCUE group.Eighteen PICU patients from January 2014 to December 2015 having no access to CCUE were recruited as control group.Both groups were treated according to the septic shock management guidelines with routine anti-shock and anti-infection therapy, as well as mechanical ventilation.Fluid management following conventional protocol was performed in the control group.While in the CCUE group, CCUE was applied to monitor the hemodynamic status for adjustment in fluid management.Results:Compared with the control group, the CCUE group had shorter mechanical ventilation time as well as less fluid intake and output within 48 hours after admission[(4.68±2.06)d vs.(7.33±0.49)d, (6.34±1.85)ml/(kg·h) vs.(8.55±0.39) ml/(kg·h), (2.47±1.22)ml/(kg·h) vs.(6.18±1.72)ml/(kg·h)] ( P<0.05). The CCUE group also had a more positive fluid balance and larger dosage of midazolam and fentanyl administration[(3.87±2.33)ml/(kg·h) vs.(2.37±2.10)ml/(kg·h), (5.62±2.39)μg/(kg·min) vs.(1.68±0.82)μg/(kg·min), (1.41±0.39)μg/(kg·h) vs.(0.95±0.56)μg/(kg·h)] ( P<0.05). The two groups showed no differences in vasoactive-inotropic score within 48 h(11.11±6.08 vs.9.90±4.12), dosage of furosemide[(1.07±0.52)mg/(kg.d) vs.(0.94±0.15)mg/(kg·d)], length of PICU stay[(10.73±7.48)d vs.(10.00±2.91)d], intubation rate after 1 hour of volume resuscitation[54.5%(12/22)vs.33.33%(6/18)] or mortality[8.3%(2/24)vs.5.3%(1/19)] ( P>0.05). Conclusion:Application of CCUE helps to optimize fluid management and shorten the ventilation time among children with septic shock in PICU.
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Objective::A multi-organ chip of intestine-liver-breast cancer was constructed based on microfluidic technology and used for pharmacokinetics-pharmacodynamics (PK-PD) study of drugs in vitro. Method::A multi-organ chip comprising a 4-layer polydimethylsiloxane (PDMS) substrate and a 2-layer poly(methyl methacrylate) (PMMA) cover was constructed by microfluidic technology. The connection between cells was investigated by staining the 21-day-grown human colon cancer cell line Caco-2 cell layer and the 3-day-grown human umbilical vein endothelial cell line HUVEC cell layer with CellTracker Red/Green and Hoechst, respectively. The transmission rates of 2 g·L-1 fluorescein sodium and 33.28 mg·L-1 propranolol acrossing the cell layer were employed to verify the function of the constructed intestinal module. The metabolic level of the liver module was investigated by comparing the inhibition rate of 125 μmol·L-1 cyclophosphamide against human breast cancer cell line MCF-7 cells treated with human hepatoma cell line HepG2 cells in a conventional well plate and chip liver module for 48 h. The secretion of albumin by HepG2 cells in the chip was detected to verify the synthesis function of hepatic module. Caco-2 cell layer, HUVEC cell layer, HepG2 cell layer, MCF-7 cell layer and dialysis membrane were assembled on the chip, the culture medium containing 55 mg·L-1 propranolol was injected into the upper channel of the chip for 4 h, and then changed into the normal culture solution. The mass concentration of propranolol in the lower circulating culture medium at each time point within 72 h was determined, and the drug-time curve was drawn. The culture medium containing 125 μmol·L-1 cyclophosphamide, 5 μmol·L-1 paclitaxel, 50 μmol·L-1 capecitabine was injected into the circulating fluid in the upper layer of the chip, in order to study the inhibition rates of the three anti-tumor drugs on the MCF-7 cell layer on the chip within 72 h, and the results were compared with those of the 96-well plate. Result::The constructed chip performed well. The Caco-2 and HUVEC cell layers were tightly connected. The transmission of fluorescein sodium and propranolol between the cell layers demonstrated that the constructed intestinal module had good absorption and transport function. The inhibition rate of MCF-7 by 125 μmol·L-1 cyclophosphamide after metabolism of HepG2 cells on the well plate was 22.12%, and the inhibition rate of MCF-7 by the unmetabolized cyclophosphamide was 1.84%. The inhibition rate of MCF-7 increased to 32.13%after injected 125 μmol·L-1 cyclophosphamide from the upper layer of the chip liver module, and the inhibition rate of MCF-7 after injection from the lower layer of the chip liver module was 7.23%. The mass concentration of propranolol on the chip changed with time, which was basically consistent with that in vivo. The inhibition rate of MCF-7 on the plate with 125 μmol·L-1 cyclophosphamide was lower than that on the chip, and the inhibition rates of MCF-7 on the plate with 5 μmol·L-1 paclitaxel and 50 μmol·L-1 capecitabine were higher than those on the chip. Conclusion::The constructed multi-organ chip of intestine-liver-breast cancer has the absorption and transport function of the intestine and the metabolic function of the liver. The chip can reflect the pharmacokinetic properties of propranolol in vivo, and can be used for pharmacodynamic studies of paclitaxel and capecitabine.