Recombinant human thrombopoietin in alleviating endothelial cell injury in sepsis.

Background: To evaluate the effect of recombinant human thrombopoietin (rhTPO) on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO. Methods: This retrospective observational study involved patients with sepsis (diagnosed according to Sepsis 3.0) admitted to Shanghai General Hospital intensive care unit from January 1, 2019 to December 31, 2022. Patients were divided into two groups (control and rhTPO) according to whether they received rhTPO. Baseline information, clinical data, prognosis, and survival status of the patients, as well as inflammatory factors and immune function indicators were collected. The main monitoring indicators were endothelial cell-specific molecule (ESM-1), human heparin-binding protein (HBP), and CD31; secondary monitoring indicators were interleukin (IL)-6, tumor necrosis factor (TNF)-α, extravascular lung water index, platelet, antithrombin III, fibrinogen, and international normalized ratio. We used intraperitoneal injection of lipopolysaccharide (LPS) to establish a mouse model of sepsis. Mice were randomly divided into four groups: normal saline, LPS, LPS + rhTPO, and LPS + rhTPO + LY294002. Plasma indicators in mice were measured by enzyme-linked immunosorbent assay. Results: A total of 84 patients were included in the study. After 7 days of treatment, ESM-1 decreased more significantly in the rhTPO group than in the control group compared with day 1 (median=38.6 [interquartile range, IQR: 7.2 to 67.8] pg/mL vs. median=23.0 [IQR: -15.7 to 51.5] pg/mL, P=0.008). HBP and CD31 also decreased significantly in the rhTPO group compared with the control group (median=59.6 [IQR: -1.9 to 91.9] pg/mL vs. median=2.4 [IQR: -23.2 to 43.2] pg/mL; median=2.4 [IQR: 0.4 to 3.5] pg/mL vs. median=-0.6 [IQR: -2.2 to 0.8] pg/mL, P <0.001). Inflammatory markers IL-6 and TNF-α decreased more significantly in the rhTPO group than in the control group compared with day 1 (median=46.0 [IQR: 15.8 to 99.1] pg/mL vs. median=31.2 [IQR: 19.7 to 171.0] pg/mL, P <0.001; median=17.2 [IQR: 6.4 to 23.2] pg/mL vs. median=0.0 [IQR: 0.0 to 13.8] pg/mL, P=0.010). LPS + rhTPO-treated mice showed significantly lower vascular von Willebrand factor (P=0.003), vascular endothelial growth factor (P=0.002), IL-6 (P <0.001), and TNF-α (P <0.001) than mice in the LPS group. Endothelial cell damage factors vascular von Willebrand factor (P=0.012), vascular endothelial growth factor (P=0.001), IL-6 (P <0.001), and TNF-α (P=0.001) were significantly elevated by inhibiting the PI3K/Akt pathway. Conclusion: rhTPO alleviates endothelial injury and inflammatory indices in sepsis, and may regulate septic endothelial cell injury through the PI3K/Akt pathway.

Long-Term Changes of Urinary Exosomal Peptide Levels After Thyroidectomy in Patients with Thyroid Cancer: A Prospective Observational Study.

Background: The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in patients with thyroid cancer to determine if levels can predict the risk of recurrence. Methods: Patients >20 years old as newly diagnosed with papillary thyroid cancer who had received a thyroidectomy were recruited. Urine samples were collected at 12 months after enrollment to the study, and 1 year later. Urine exosomes containing different peptides were identified and compared. Results: A total of 70 patients were enrolled in the study, and were classified by the interval between surgery and enrollment: 42 patients with < 5 years between surgery and enrollment, 14 patients between 5-10 years, and 14 patients longer than 10 years. No recurrence was observed in any patient during the 2 years after enrollment. No significant differences were found in the levels of serum proteins or urine exosomal peptides between groups, or between intervals. Known risk factors for high-risk thyroid cancer had only a mild correlation with serum protein levels and urine exosomal peptides. Conclusion: Our study revealed the long-term basal fluctuation ranges of serum proteins and urine exosomal peptides in patients with thyroid cancer who underwent thyroidectomy. For high-risk patients after thyroidectomy, concentrations of serum proteins or urine exosomal peptides within the ranges may indicate there is a lower risk of thyroid cancer recurrence during long-term follow-up. Trial Registration: ClinicalTrials.gov: NCT03488134.

Clinical evaluation and management of badminton-related eye injuries: a retrospective case series.

BACKGROUND: To describe the clinical features, visual outcomes, management, and complications of ocular injury in badminton and investigate risk factors associated with visual impairment. METHODS: Data on patients injured while playing badminton admitted to Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital, Fudan University between January 2018 to December 2020.The relationship between visual acuity (VA) and demographic and clinical variables was also analyzed. Patients were managed medically or surgically as per their needs, followed up for at least 18 months. The visual outcomes were predicted using ocular trauma score (OTS), predicted outcomes were compared with actual outcomes using statistical tests. RESULTS: This study involved 102 patients (78 men, 24 women) with a mean age of 43.8 ± 16.1 years (7-71 years). Of these, 93 patients had closed-globe injuries and 9 had open-globe injuries. Vision-threatening findings included lens subluxation(31.4%),retinal detachment(13.7%),hyphema(12.7%). Open-globe injury had significantly lower presenting VA and final VA (P= 0.0164, 0.0053).Final VA was found to be correlated with presenting VA, maculopathy, retinal detachment, and OTS (P=0.0000, 0.0494, 0.0001, 0.0000 respectively), it was worse in patients who were under 20 years of age and were female. OTS prediction was not significantly different when compared with actual visual outcomes postoperatively in OTS3, OTS4, and OTS5 (P > 0.05),while the prognosis of patients with OTS1 and OTS2 was better than OTS study (P=0.001, 0.007, respectively). CONCLUSION: Badminton-related closed-globe injuries were more frequent; open-globe injuries were usually more serious. Younger and female patients have poorer visual recovery prognoses. OTS was found to be a reliable tool for predicting visual outcomes.

Paraquat is an agonist of STIM1 and increases intracellular calcium levels.

Paraquat (PQ) is an efficient herbicide but leads to high mortality with no antidote in mammals. PQ produces reactive oxygen species (ROS), leading to epithelial-mesenchymal transition (EMT) for pulmonary fibrosis in type II alveolar (AT II) cells. Intriguingly, strategies reducing ROS exhibit limited therapeutic effects, indicating other targets existing for PQ toxicity. Herein we report that PQ is also an agonist for STIM1 that increases intracellular calcium levels. Particularly, PQ promotes STIM1 puncta formation and association with TRPC1 or ORAI for extracellular calcium entry and thus intracellular calcium influx. Further studies reveal the importance of P584&Y586 residues in STIM1 for PQ association that facilitates STIM1 binding to TRPC1. Consequently, the STIM1-TRPC1 route facilitates PQ-induced EMT for pulmonary fibrosis as well as cell death. Our results demonstrate that PQ is an agonist of STIM1 that induces extracellular calcium entry, increases intracellular calcium levels, and thus promotes EMT in AT II cells.

Development of ligand modified erythrocyte coated polydopamine nanomedicine to codeliver chemotherapeutic agent and oxygen for chemo-photothermal synergistic cancer therapy.

The use of conventional chemotherapy often faces limitations such as severe side effects, weak tumor tissue specificity, and the development of multidrug resistance. To conquer these challenges, numerous novel drug carriers have been designed in recent years. However, due to the complex processes of tumor development, metastasis and recurrence, single chemotherapy cannot fulfill the goals of clinical diverse treatment. In this work, by utilizing the inherent characteristics of surface-modified erythrocyte and the outstanding photothermal conversion capability of polydopamine (PDA), we designed and constructed a biomimetic multifunctional nanomedicine DPPR NPs to codeliver chemotherapeutic agent doxorubicin (DOX) and oxygen. The results showed that DPPR NPs exhibited inspiring features including nanoscale droplet size, good physicochemical stability, and sustained, pH-, and NIR triggered drug release behavior. It can dramatically prolong the systematic circulation time and elevated the drug accumulated level in the tumor site. Moreover, DPPR NPs could be effectively internalized into tumor cells and destroyed the intracellular redox balance to mediate cell apoptosis. It exerted excellent in vivo tumor targeting effect, photothermal conversion efficiency, ultrasound imaging responses, antitumor efficacy, and good compatibility. In summary, DPPR NPs provide a biomimetic drug delivery platform to organically combine chemotherapy and photothermal therapy for precise cancer treatment.

Risk factors and a prediction model for sepsis: A multicenter retrospective study in China.

Background: Sepsis is typically associated with poor outcomes. There are various risk factors and predictive models for sepsis based on clinical indicators. However, these models are usually predictive of all critical patients. This study explored the risk factors for 28-day outcomes of patients with sepsis and developed a prognosis prediction model. Methods: This was a multicenter retrospective analysis of sepsis patients hospitalized in three intensive care units (ICUs) from September 1st 2015, to June 30th 2020. Demographic, clinical history, and laboratory test data were extracted from patient records. Investigators explored the risk factors affecting 28-day sepsis prognosis by univariate analysis. The effects of confounding factors were excluded by multivariate logistic regression analysis, and new joint predictive factors were calculated. A model predicting 28-day sepsis prognosis was constructed through data processing analysis. Results: A total of 545 patients with sepsis were included. The 28-day mortality rate was 32.3%. Risk factors including age, D-dimer, albumin, creatinine, and prothrombin time (PT) were predictive of death from sepsis. The goodness-of-fit value for this prediction model was 0.534, and the area under the receiver operating characteristic curve was 0.7207. Further analysis of the immune subgroups (n=140) revealed a significant decrease in CD3+, CD4+CD8-, and CD4+CD29+ memory effector T lymphocytes and an increase in CD56+ natural killer (NK) cells in the hypoalbuminemia group compared with the normal albumin group (65.5 vs. 58.3, P=0.005; 41.2 vs. 32.4, P=0.005; 21.8 vs. 17.1, P=0.029; 12.6 vs. 17.6, P=0.004). Conclusions: Risk factors for 28-day sepsis mortality include age, D-dimer, creatinine, PT, and albumin. A decrease in albumin level may exacerbate immunosuppression in patients with sepsis. This study establishes a prediction model based on these indicators, which shows a good degree of calibration and differentiation. This model may provide good predictive value for clinical sepsis prognosis.

Urinary Exosomal Tissue TIMP and Angiopoietin-1 Are Preoperative Novel Biomarkers of Well-Differentiated Thyroid Cancer.

Finding non-invasive and sensitive biomarkers for early screening of high-risk patients remains important in clinical practice. A higher concentration of urine exosomal thyroglobulin protein was found in late-stage patients with thyroid carcinoma compared to those with early stage in our previous study. This prospective study aims to find new prognostic biomarkers before surgery for decision-making with this platform. We enrolled patients newly diagnosed with papillary and follicular cancer from 2017 to 2018. Preoperative urine samples were collected and the exosomal proteins were analyzed. The association of the concentration of urine exosomal proteins with lymph node metastasis and MACIS score (metastasis, age, completeness of resection, invasion, and size) was analyzed with multiple logistic regression. In total, 21 patients were included, with a mean age of 51.29 ± 10.29 years and a majority of female patients (85.71%). The concentration of urine exosomal TIMP (tissue inhibitor of metalloproteinase) was significantly higher in patients with lymph node metastasis (p = 0.01). Multiple logistic regression analysis showed association of urine exosomal TIMP (adjusted odds ratio (aOR): 3.09, 95% confidence interval (CI): 0.99-9.6, p = 0.052), angiopoietin-1 (aOR: 2.24, 95% CI: 0.97-5.15, p = 0.058) with lymph node metastasis. However, no association was noted between MACIS score and various urine exosomal protein candidates. Preoperative urine exosomal data could suggest certain peptides having the potential as prognostic indicators for screening patients with high-risk before surgery. Further study with a large cohort and long follow-up is needed to identify the application of urine exosomal proteins on prognostic prediction.

m6A modification regulates lung fibroblast-to-myofibroblast transition through modulating KCNH6 mRNA translation.

Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal lung disease characterized by progressive and non-reversible abnormal matrix deposition in lung parenchyma. Myofibroblasts originating mainly from resident fibroblasts via fibroblast-to-myofibroblast transition (FMT) are the dominant collagen-producing cells in pulmonary fibrosis. N6-methyladenosine (m6A) modification has been implicated in various biological processes. However, the role of m6A modification in pulmonary fibrosis remains elusive. In this study, we reveal that m6A modification is upregulated in a bleomycin (BLM)-induced pulmonary fibrosis mouse model, FMT-derived myofibroblasts, and IPF patient lung samples. Lowering m6A levels through silencing methyltransferase-like 3 (METTL3) inhibits the FMT process in vitro and in vivo. Mechanistically, KCNH6 is involved in the m6A-regulated FMT process. m6A modification regulates the expression of KCNH6 by modulating its translation in a YTH-domain family 1 (YTHDF1)-dependent manner. Together, our study highlights the critical role of m6A modification in pulmonary fibrosis. Manipulation of m6A modification through targeting METTL3 may become a promising strategy for the treatment of pulmonary fibrosis.

Biomarkers for the diagnosis of sepsis-associated acute kidney injury: systematic review and meta-analysis.

BACKGROUND: With the development of new techniques, blood and other humoral biomarkers have become increasingly important in the diagnosis of sepsis-associated acute kidney injury (AKI). We aimed to review and summarize the biomarkers associated with the diagnosis of sepsis-associated AKI. METHODS: We performed a systematic review in PubMed, Embase, Web of Science, Cochrane and CNKI literature databases. Chinese and English articles published before January 30, 2021. We extracted information on the sensitivity and specificity of biomarkers to diagnose sepsis-associated AKI, the sample size of individuals with sepsis-associated AKI, the demographic variables, the diagnostic criteria and the sample acquisition protocol. Revman 5.3 software was used to analyze data. The sources of heterogeneity of included studies main were different diagnostic criteria for sepsis and AKI, time of sample collection and Patients came from different departments. We defined the inclusion of related studies by using PICOs (Patient, Intervention, Comparison and Outcome) criteria, in particular the design of studies to be included. P: Patients of sepsis. I: Patients of sepsis-associated AKI. C: Patients without sepsis-associated AKI. O: Diagnosis of sepsis associated kidney injury. RESULTS: A total of 1,227 articles, including 42 studies, were identified. Increases in urine and serum neutrophil gelatinase-related lipid carrier protein (NGAL), urinary interleukin-18, urinary Kim-1, urinary Netrin-1, urinary sCD163, serum estradiol levels, and serum soluble thrombolytic regulatory protein were most strongly correlated with the diagnosis of sepsis-associated AKI. The SROC of urinary KIM-1 ranked first, followed by the other biomarkers: urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18. According to the sample size, the SROC values of urinary NGAL, blood NGAL, urinary IL-18 and urinary KIM-1 were 0.907, 0.857, 0.861 and 0.931, respectively. The sequence was still urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18. CONCLUSIONS: According to the SROC curve area, the diagnostic sequence of sepsis-associated AKI biomarkers was urinary Kim-1 > urinary NGAL > blood NGAL > urinary IL-18. This meta-analysis provided diagnostic features of blood and urine biomarkers based on their association with the diagnosis of sepsis-associated AKI.

A comparison of visual acuity measured by ETDRS chart and Standard Logarithmic Visual Acuity chart among outpatients.

AIM: To compare the results of visual acuity (VA) measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart, 5 m Standard Logarithm Visual Acuity (5SL) chart, and 2.5 m Standard Logarithm Visual Acuity (2.5SL) chart in outpatients of age 12-80y. METHODS: Each patient (totally 2000 outpatients) had both eyes tested with ETDRS chart at 4 m, 5SL chart at 5 m, and 2.5SL chart at 2.5 m in random order. The VA values of outpatients were categorized by ages. VA values were expressed by logMAR recording method. RESULTS: The mean VA results of ETDRS charts, 5SL, and 2.5SL chart were 0.52±0.28, 0.50±0.30, and 0.46±0.28 logMAR, respectively. There was a statistically significant difference in the three eye charts in the whole group (P<0.001). For all subjects, the correlation of VA tested with three charts was statistically significant (Spearman correlation coefficient=0.944, 0.937, 0.946, all P<0.001). Bland-Altman analysis shows the 95% limits of agreement between the 5SL and 2.5SL chart were -0.182 to 0.210, -0.139 to 0.251, and -0.151 to 0.235 logMAR, respectively). CONCLUSION: The agreement between the three eye charts is not high. The VA measured by 5SL chart is slightly better than that by ETDRS chart and 5SL chart would be a suitable alternative when ETDRS chart are not available in the clinical situation. The VA measured by 2.5SL chart is about 0.5 line better than VA tested with ETDRS chart, which may overestimate VA.

Early chest computed tomography to diagnose COVID-19 from suspected patients: A multicenter retrospective study.

Objective: The purpose of this study was to distinguish the imaging features of COVID-19 from those of other infectious pulmonary diseases and evaluate the diagnostic value of chest CT for suspected COVID-19 patients. Methods: Adult patients suspected of COVID-19 aged >18 years who underwent chest CT scans and reverse-transcription polymerase chain reaction (RT-PCR) tests within 14 days of symptom onset were enrolled. The enrolled patients were confirmed and grouped according to the results of the RT-PCR tests. The basic demographics, single chest CT features, and combined chest CT features were analyzed for the confirmed and nonconfirmed groups. Results: A total of 130 patients were enrolled, with 54 testing positive and 76 testing negative. The typical CT imaging features of the positive group were ground glass opacities (GGOs), the crazy-paving pattern and air bronchogram. The lesions were mostly distributed bilaterally and close to the lower lungs or the pleura. When features were combined, GGOs with bilateral pulmonary distribution and GGOs with pleural distribution were more common among the positive patients, found in 31 (57.4%) and 30 patients (55.6%), respectively. The combinations were almost all statistically significant (P < .05), except for the combination of GGOs with consolidation. Most combinations presented relatively low sensitivity but extremely high specificity. The average specificity of these combinations was approximately 90%. Conclusions: The combinations with GGOs could be useful in the identification and differential diagnosis of COVID-19, alerting clinicians to isolate patients for prompt treatment and repeat RT-PCR tests until the end of incubation.

[Optic nerve sheath diameter and eyeball transverse diameter as a useful tool for the clinical prognosis in patients with stroke during hospitalization].

OBJECTIVE: To evaluate the prognostic value of ultrasonographic measurement of optic nerve sheath diameter (ONSD) and ONSD/eyeball transverse diameter (ETD) ratio in stroke patients during hospitalization. METHODS: Adult patients with stroke (ischemic stroke or hemorrhagic stroke) admitted to department of critical care medicine of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from November 2017 to November 2018 were enrolled. On the day of admission, ONSD and ETD (retina-retina at 3 mm behind the globe along) were detected by ultrasound, the ONSD/ETD ratio was calculated, and the baseline data and outcomes were recorded. Patients were divided into survival group and death group according to their survival status. Locally weighted scatterplot smoothing (LOWESS) and the receiver operating characteristic (ROC) curve were used to calculate the thresholds of ONSD and ONSD/ETD. The correlation between ONSD, ONSD/ETD and prognosis were assessed. RESULTS: Thirty-eight of 83 patients (45.8%) survived and were discharged from the hospital, while 45 patients died (54.2%). There were significant differences in Glasgow coma score (GCS), shifting of the middle structure, ONSD and ONSD/ETD between the death group and the survival group [GCS: 4.7±2.8 vs. 11.0±3.2, shifting of the middle structure (mm): 5.8±5.9 vs. 1.3±2.6, ONSD (mm): 5.5±0.4 vs. 4.4±0.5, ONSD/ETD: 0.25±0.02 vs. 0.20±0.02, all P < 0.05]. LOWESS and ROC curve analysis suggested thresholds of ONSD and ONSD/ETD for predicting adverse prognosis of stroke patients were 5.0 mm and 0.25, respectively. By adjusting the influence of confounding factors on prognosis, a prediction model based on ONSD was established, and the ROC curve was drawn. The area under the curve (AUC) was 0.978, the optimal predictive point of the model was 0.870, the sensitivity was 89%, and the specificity was 100%. The ONSD/ETD prediction model was also obtained, and the AUC was 0.988, the optimal prediction threshold of the model was 0.768, and the sensitivity for predicting adverse clinical prognosis was 94%, and the specificity was 97%. The stability of ONSD/ETD was better than that of ONSD. ONSD coefficient of variation was 0.14, and ONSD/ETD coefficient of variation was 0.13. CONCLUSIONS: ONSD and ONSD/ETD were significantly correlated with the prognosis of critical patients with stroke. The mortality increased significantly in patients with an ONSD greater than 5.0 mm and ONSD/ETD greater than 0.25. ONSD and ONSD/ETD may be promising tools for early assessment of clinical outcomes in these patients.

The effect of recombinant human thrombopoietin (rhTPO) on sepsis patients with acute severe thrombocytopenia: a study protocol for a multicentre randomised controlled trial (RESCUE trial).

BACKGROUND: Sepsis is still a common critical disease with high morbidity and mortality in intensive care unit. Despite published guidelines for sepsis, development of antibiotic therapy and advanced organ support technologies, the mortality of sepsis patients is still 25% or more. It is necessary to distinguish the subtypes of sepsis, and the targeted therapy for the patients need to be explored. Platelets have various biological functions in hemostasis and thrombosis, host defense, inflammatory/immune responses and tissue repair/regeneration. Moreover, severe thrombocytopenia or sustained thrombocytopenia was closely associated with multiply organ dysfunction and higher mortality in sepsis patients. The clinical therapies for thrombocytopenia are platelet transfusion and platelet-elevating drugs. However, platelet transfusion has many defects in clinical practice in sepsis patients, and the impact of platelet-elevating drugs for sepsis patients is still unclear. RESCUE trial is aim to explore the effect of a platelet-elevating drug, recombinant human thrombopoietin (rhTPO), as an effective rescue therapy on sepsis patients with acute severe thrombocytopenia. METHODS: It is a randomized, open-label, multi-center, controlled trial in 5 tertiary academic hospitals including medical, surgical or general ICUs. In this study, a total of 200 sepsis patients with severe thrombocytopenia will be randomly assigned in a 1:1 ratio to the control and rhTPO group. The patients will be followed up to 28 days after randomization. All patients in two groups receive the same treatment based on the guideline of Surviving Sepsis Campaign. Primary outcome is 28-day mortality. Secondary outcomes are the changes of PCs, blood transfusion, biomarkers of infection and organ function, days free from advanced organ support, drug-related adverse events, the length of ICU and hospital stay. DISCUSSION: RESCUE trial is the first randomized controlled trial to explore the impact of rhTPO for severe thrombocytopenia in sepsis patients diagnosed by sepsis-3.0 standard. Furthermore, RESCUE trial results will be of significant clinical value on the targeted therapy and add clinical evidence that rhTPO is an effective rescue therapy for these sepsis patients. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02707497. Registered Date: March 3rd, 2016. Protocol Version 3. Protocol Date: January 25th, 2019.

An Improved Multi-temporal and Multi-feature Tea Plantation Identification Method Using Sentinel-2 Imagery.

As tea is an important economic crop in many regions, efficient and accurate methods for remotely identifying tea plantations are essential for the implementation of sustainable tea practices and for periodic monitoring. In this study, we developed and tested a method for tea plantation identification based on multi-temporal Sentinel-2 images and a multi-feature Random Forest (RF) algorithm. We used phenological patterns of tea cultivation in China's Shihe District (such as the multiple annual growing, harvest, and pruning stages) to extracted multi-temporal Sentinel-2 MSI bands, their derived first spectral derivative, NDVI and textures, and topographic features. We then assessed feature importance using RF analysis; the optimal combination of features was used as the input variable for RF classification to extract tea plantations in the study area. A comparison of our results with those achieved using the Support Vector Machine method and statistical data from local government departments showed that our method had a higher producer's accuracy (96.57%) and user's accuracy (96.02%). These results demonstrate that: (1) multi-temporal and multi-feature classification can improve the accuracy of tea plantation recognition, (2) RF classification feature importance analysis can effectively reduce feature dimensions and improve classification efficiency, and (3) the combination of multi-temporal Sentinel-2 images and the RF algorithm improves our ability to identify and monitor tea plantations.

Color Doppler Flow Imaging of Retrobulbar Ocular Blood Flow Changes in Retinal Artery Occlusions Caused by Cosmetic Facial Filler Injections.

PURPOSE: This study aimed to evaluate the effects of retinal artery occlusions caused by cosmetic facial filler injections on the retrobulbar blood flow parameters. METHODS: This was a retrospective, noncomparative case series. Ten consecutive patients with fundus artery occlusions caused by facial filler injections were evaluated using color Doppler flow imaging (CDFI). The peak systolic velocity and end diastolic velocity of the ophthalmic artery, central retinal artery, and posterior ciliary arteries were determined. The clinical features, including the filler material, injection site, best-corrected visual acuity, fundus fluorescein angiography, and associated ocular and systemic manifestations were also collected. RESULTS: Injected materials included autologous fat (7 cases) and hyaluronic acid (3 cases). In 6 of the patients with ophthalmic artery occlusions, the CDFI showed no or drastic declines in the retrobulbar blood flow in the ophthalmic artery, central retinal artery, and posterior ciliary arteries. In 3 of the patients with central retinal artery occlusions, the CDFI showed no or a grossly decreased retrobulbar blood flow in the central retinal artery. In one patient with anterior ischemic optic neuropathy, the CDFI showed decreased end diastolic velocities and increased pulsatility and resistance indices in the central retinal artery, posterior ciliary arteries, and ophthalmic artery. During the follow-up period, the retrobulbar blood flow recovered to some degree. Overall, ophthalmic artery occlusion patients receiving autologous fat may have neurologic complications. CONCLUSIONS: The results suggest that the retrobulbar ocular blood flows measured with CDFI were distinctly different in the different types of ophthalmic artery occlusion. Color Doppler flow imaging could provide a practicable and convenient method for the diagnosis and follow up of retinal artery occlusions caused by cosmetic facial filler injections.

Effects of different doses of dexmedetomidine on heart rate and blood pressure in intensive care unit patients.

The aim of the present study was to observe and compare the sedative effect of different doses of DEX on heart rate (HR) and blood pressure (BP) in critically ill patients admitted to intensive care units (ICUs). The study included patients that were retained in ICUs and required sedation between January and March 2014. Patients were excluded if they had a BP of >200 mmHg, a HR of <60 bpm or were in a state of shock. The included patients were randomized into three groups: Group A, 1.0 µg/kg/10 min DEX; group B, 0.5 µg/kg/10 min DEX; and group C, 0.4 µg/kg/h DEX. After receiving these initial designated doses of DEX via an intravenous (IV) infusion pump for 10 min, the patients were maintained continuously at an identical dose of 0.4 µg/kg/h DEX. Ramsay score, HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), breathing rate (BR) and peripheral capillary oxygen saturation (SpO2) were recorded prior to the IV pump infusion and at 2, 4, 6, 8, 10, 60, 120, 180 and 240 min following infusion. Patients in groups A and B achieved sedation more rapidly compared with those in group C (P<0.05). HR decreased more significantly at 8 and 60 min after the initial IV pump infusion with DEX in groups A and B compared with group C (P<0.05). SBP decreased significantly at 10 min after IV pump infusion in group A compared with groups B and C (P<0.05). No significant difference existed in the SBP reduction trend between the three groups during the maintenance period. Therefore, the routine dose of DEX (0.4 µg/kg/h) provides an ideal sedative effect in ICU patients. The recommended loading dose for a more rapid sedation is 0.5 µg/kg/h. High loading doses of DEX via IV pump infusion should be avoided in elderly individuals, patients with acute exacerbation of chronic obstructive pulmonary disease and anemic patients, in whom combination medication, such as midazolam or propofol, may be considered when necessary.

Citrate induces apoptosis of the acute monocytic leukemia U937 cell line through regulation of HIF-1α signaling.

The present study aimed to investigate the anti-tumor effect of citrate on acute monocytic leukemia (AML) and its mechanisms. The apoptosis of the AML cell line, U937, was assessed by MTT and Hoechst staining, the expression of Bcl-2, caspases-3 and -9, hypoxia-inducible factor 1α (HIF­1α) and its target gene GLUT-1, were assayed by western blotting and the role of HIF­1α was evaluated through siRNA. The results showed that citrate inhibits the expression of Bcl-2, while it induces the activation of caspases-3 and -9. In addition, citrate induces U937 apoptosis in a dose- and time-dependent manner by regulating the expression of HIF­1α and its downstream target GLUT-1. The results suggest that citrate performs an anti-acute monocytic leukemia action by targeting HIF­1α signaling and may be a promising clinical approach.