Abstract:Objective To investigate the effect of target-and-endpoint protocol on the resuscitation of septic patients.Methods This is a retrospective study performed at the Peking Union Medical College Hospital Intensive Care Unit. We enrolled 545 septic patients who needed vasopressors on at least the first day of ICU admission. The general characteristics, blood lactate level, mean arterial pressure (MAP), central venous pressure (CVP) and saturation of central venous oxygen (ScvO2) at admission and 6, 24 hours after admission were collected. The parameters at different time points were compared. Lactate clearance rate and in-hospital mortality were analyzed.Results The 6-hour lactate clearance rate was 21.6% (IQR, 8.6%-39.0%), and in-hospital mortality was 9.4%. For patients with low CVP values (<8 mm Hg, 1 mm Hg=0.133 kPa) at admission, CVP increased significantly at 6 hours after admission (5.4±1.6 mm Hg vs. 7.7±2.6 mm Hg, P<0.001). For patients with low MAP (<75 mm Hg) at admission, the MAP values increased significantly at 6 hours (64.2±7.1 mm Hg vs. 82.2±13.1 mm Hg, P<0.001). For patients with low ScvO2 value (<70%) at admission, the ScvO2 value increased significantly at 6 hours (61.9%±7.0% vs. 71.9%±7.8%, P<0.001). No difference was found between the values at 6 hours and the corresponding values at 24 hours after admission. For patients with high CVP values (≥8 mm Hg) at admission, CVP decreased significantly at 6 hours (11.3±4.0 mm Hg vs. 10.3±2.9 mm Hg, P<0.001). For patients with high MAP (≥75 mm Hg) at admission, the MAP values decreased significantly at 6 hours (94.2±13.9 mm Hg vs. 89.4±11.4 mm Hg, P<0.001). For patients with high ScvO2 value (≥70%) at admission, the ScvO2 values decreased significantly at 6 hours (76.8%±4.2% vs. 72.9%±7.3%, P<0.001). No difference was found between the values at 6 hours and the corresponding values at 24 hours.Conclusions This study suggested that in the resuscitation of sepsis and septic shock patients in the ICU, the target values did not need to be within the “normal range” recommended by early-goal directed therapy. The “target-and-endpoint” protocol, which aimed for personalized goals, deserves more consideration.
Abstract:Objective To investigate the role of RNA binding protein—upstream-of-N-Ras (UNR) in the development of glioma and its molecular mechanism.Methods First, bioinformatics analysis of CGGA database was performed to detect UNR expression level and prognosis of patients with glioma. Western blot and real-time PCR were used to detect UNR expression level in glioma cell lines and tissues. Next, UNR siRNAs were transfected in glioma cells, and MTS assay and scratch wound-healing assay were used to detect changes in cell proliferation and migration. Then, the candidate UNR target mRNAs were identified by analyzing the sequencing data of UNR iCLIP-seq, RNA sequencing and ribosome profiling databases of human melanoma. RNA immunoprecipitation and biotin pull-down assays were used to identify the UNR target mRNAs in glioma cells. Finally, western blot was used to detect the effect of UNR knockdown on ribosomal protein L9 (RPL9) and RPL9 protein expression level in glioma cell lines. RPL9 siRNA was transfected in A172 and T98G and the expression of vimentin in the cells was detected with western blot.Results Bioinformatics analysis showed that UNR mRNA expression level was significantly higher in high-grade glioma [Grade Ⅱ (n=126), Grade Ⅲ (n=51), Grade Ⅳ (n=128), P<0.001]. UNR high expression levels were associated with poor prognosis (P=0.0177). UNR had high expression level in glioma cell lines and patient samples compared with normal cell lines and normal brain samples (P<0.01). Knockdown of UNR inhibited glioma cells migration (P<0.05), but did not inhibit glioma cells growth in three glioma cell lines. UNR binded the 3’ untranslated region (UTR) of PTEN and RPL9 mRNAs. RPL9 protein was significantly highly expressed in most glioma cell lines (n=9) and knockdown of UNR resulted in a downregulation of RPL9 protein expression. Epithelial-mesenchymal transition (EMT)-related marker—vimentin was positively regulated by RPL9.Conclusions UNR could bind to the 3’UTR of PTEN and RPL9 in glioma cell lines, therefore promoting glioma cell migration and regulating the expression of RPL9. Here, we establish a link between UNR and RPL9 protein, which will provide new ideas for the further study of glioma.
Keywords:UNR;glioma;migration;ribosomal protein L9;vimentin
Abstract:Objective To determine whether urinary myeloperoxidase to creatinine ratio (MCR) can serve as a marker for diagnosis of urinary tract infection (UTI).Methods Patients suspected of UTI were consecutively enrolled and further divided into the culture positive and the sterile groups according to urine culture results. Subsequently, MCR, white blood cell (WBC) and bacteria in the urinary samples from patients were detected and compared between the two groups.Results Finally, 253 patients were enrolled including 157 urine culture positive patients and 96 urine culture negative patients (sterile group). After logarithmic transformation in 2 as the base, the MCR, WBC, and bacteria were separately presented as log2MCR, log2WBC(quantitative) , and log2bacteria. The values of log2MCR(8.6±2.5 vs. 5.4±1.5, t=-12.453, P=0.001), log2WBC(quantitative) (8.0±2.5 vs. 5.2±1.8, t=-10.332, P=0.001), log2bacteria (11.4±2.5 vs. 8.2±2.8, t=-9.297, P=0.001) and WBC (semi-quantitative) [2 (interquartile range 1, 3) vs. 1 (interquartile range 0.5, 1), Z=-7.580, P=0.001] showed significant difference between the urine culture positive group and the sterile group. Among the urine culture positive group, the values of log2MCR of the gram positive and gram negative subgroups were 7.2±2.5 and 9.0±2.4 (t=4.016, P=0.001), respectively. The correlation between log2MCR and log2WBC (quantitative), log2bacteria, WBC (semi-quantitative) was 0.708 (Pearson correlation, P=0.001), 0.381 (Pearson correlation, P=0.001), and 0.606 (Spearman correlation, P=0.001), respectively. Conclusions MCR is positively correlated with WBC counts and could be served as a promising biomarker for diagnosis of UTI. MCR could be even used for initial inference of infectious bacteria types of UTI.
Abstract:Objective To analyze characteristics of high altitude pulmonary edema (HAPE) in Chinese patients.Methods We performed a retrospective study of 98 patients with HAPE. We reviewed the medical records and summarized the clinical, laboratory and imaging characteristics of these cases, and compared the results on admission with those determined before discharge.Results Forty-eight (49.0%) patients developed HAPE at the altitude of 2800 m to 3000 m. Ninty-five (96.9%) patients were man. Moist rales were audible from the both lungs, and moist rales over the right lung were clearer than those over the left lung in fourteen patients. The white blood cells [(12.83±5.55) versus (8.95±3.23) ×10 9/L, P=0.001)] as well as neutrophil counts [(11.34±3.81) versus (7.49±2.83)×10 9/L, P=0.001)] were higher, whereas the counts of other subsets of white blood cells were lower on admission than those after recovery (all P<0.05). Serum levels of alkaline phosphatase (115.8±37.6 versus 85.7±32.4 mmol/L, P=0.020), cholinesterase (7226.2±1631.8 versus 6285.3±1693.3 mmol/L, P=0.040), creatinine (85.2±17.1 versus75.1±12.8 mmol/L, P=0.021), uric acid (401.9±114.2 versus 326.0±154.3 mmol/L, P=0.041), and uric glucose (7.20±1.10 versus 5.51±1.11 mmol/L, P=0.001) were higher, but carbondioxide combining power (CO2CP, 26.7±4.4 versus 28.9±4.5 mmol/L, P=0.042) and serous calcium (2.32±0.13 versus 2.41±0.10 mmol/L, P=0.006) were lower on admission. Arterial blood gas results showed hypoxemia and respiratory alkalosis on admission. Conclusions In the present research, men were more susceptible to HAPE than women, and in the process of HAPE, the lesions of the right lung were more serious than those of the left lung. Some indicators of routine blood test and blood biochemistry of HAPE patients changed.
Abstract:Objective To evaluate senile plaque formation and compare the sensitivity of three different β-amyloid (Aβ) labeling methods (antibody staining, Gallyas silver staining, and thioflavin-S staining) to detect Aβ deposition.Methods APPswe/PSEN1dE9 transgenic mice (APP/PS1) of different ages were used to examine spatiotemporal changes in Aβ plaque deposition. Antibody staining, Gallyas silver staining, and thioflavin-S staining were used to detect Aβ plaque deposition in the same brain region of adjacent slices from model mice, and the results were compared.Results With aging, Aβ plaques first appeared in the cortex and then the deposition increased throughout the whole brain. Significantly greater plaque deposition was detected by 6E10 antibody than that analyzed with Gallyas silver staining or thioflavin-S staining (P<0.05). Plaque deposition did not show significant difference between the APP/PS1 mice brains assayed with Gallyas silver staining and ones with thioflavin-S staining (P=0.0033).Conclusions The APP/PS1 mouse model of Alzheimer’s disease could mimick the progress of Aβ plaques occurred in patients with Alzheimer’s disease. Antibody detection of Aβ deposition may be more sensitive than chemical staining methods.
Abstract:Programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) is a significant immune checkpoint, and the dysfunction of this axis contributes to tumor metastasis and immune escape. PI3K/Akt/mTOR and MAPK signal network induces PD-1/PD-L1 expression and facilitates tumor progression. Transcriptional factors such as hypoxia induced factors, PTEN, p53, CDK5, BRD4, STAT modulate PD-1/PD-L1 expression. PD-1/PD-L1 level is also regulated via epigenetic and post-translational manner. The underlying mechanisms mentioned above may provide potential targets for tumor treatment. At present, the combination therapy of PD-1/PD-L1 monoclonal antibodies plus small molecular inhibitors has achieved good outcomes in tumor treatment.
Keywords:programmed cell death protein 1/programmed death ligand 1;immunotherapy;regulation;clinical trial;inhibitors
Abstract:Skin reaction or dermatological toxicities induced by immunotherapy is common. It usually manifests skin rash or erythema and can be cured by skin lotion or steroid. Nivolumab, a human IgG4 programmed cell death protein 1 (PD-1) inhibitor, blocks T cells activation preventing signal and allows the immune system to clear cancer cells. Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA, with less than 10% unusual skin reaction, like sensory neuropathy, peeling skin, erythema multiforme, vitiligo, and psoriasis. Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity. The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies, but the risk of side effects may be high. We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy. The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events. Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.
Keywords:skin reaction;nivolumab;immunotherapy;radiotherapy;non-small cell lung cancer
Abstract:We performed contrast-enhanced T2 fluid-attenuated inversion recovery (T2-FLAIR) and dynamic contrast enhanced MRI to illustrate the imaging characteristics of one case of hemangioblastoma. T2-FLAIR showed a large cyst located in the right cerebellum with mural nodule. The intensely enhancing cyst wall was observed on enhanced T2-FLAIR images acquired from 5.6 to 23 minutes after contrast administration, and quantitative dynamic contrast enhanced-MRI demonstrated that both the cyst wall and mural nodule presented high Ktrans, Kep and Ve values compared with the contralateral normal cerebellar tissues. The cyst showed gradual enhancement and reached the highest signal intensity at 67 minutes after contrast administration on enhanced T2-FLAIR images. In conclusion, early enhancement of cyst wall on T2-FLAIR might be the characteristic imaging findings for cystic hemangioblastoma, which may assist in the diagnosis of hemangioblastoma preoperatively.
Abstract:Choledochocele is a congenital abnormality of the biliary system, which characterized by a cystic dilatation of intramural segment of the distal common bile duct. Choledochocele manifests as cystic lesions in the duodenal lumen and resembles duodenal duplication cysts in imaging. We reported a patient with choledochocele. Magnetic resonance cholangiopancreatography showed a thin-walled sac in the duodenal cavity and a fine tubular structure connecting with the end of the common bile duct. Magnetic resonance cholangiopancreatography is a noninvasive and convenient technique in the diagnosis of choledochocele.