Early identification value of quick sequential organ failure assessment score in patients with sepsis of different ages / 中华危重病急救医学

Objective:To investigate the value of quick sequential organ failure assessment (qSOFA) score in early identification for sepsis patients of different ages.Methods:A retrospective study was conducted. The clinical data of 1 529 patients with suspected infection in emergency department of Changshu No.2 People's Hospital from September 2017 to March 2020 were collected. All patients were assessed for qSOFA score, and the diagnosis and treatment were recorded. Sepsis-3 was defined as the diagnostic criteria for sepsis. All the patients were divided into five groups according to age, youth group (< 45 years old), middle-aged group (45-59 years old), presenile group (60-74 years old), elderly group (75-89 years old), and longevity group (≥90 years old). The patients' examination results, diagnosis and treatment status were collected. The distribution of different scores of qSOFA was analyzed to calculate the sensitivity, specificity, positive predictive value and negative predictive value of different qSOFA scores for the diagnosis of sepsis in patients with suspected infection of different ages. The receiver operator characteristic curve (ROC curve) was drawn to analyze the diagnostic value of qSOFA score for sepsis in patients with suspected infection at different ages.Results:Of 1 529 suspected infection patients, there were 67 patients in youth group, 129 patients in middle-aged group, 465 patients in presenile group, 778 patients in elderly group and 90 patients in longevity group. There were significant differences in lactic acid (Lac), total bilirubin (TBil), creatinine (Cr), qSOFA score and the increased value of SOFA score compared with the basic value (ΔSOFA) among the suspected infection patients at different ages. Among suspected infection patients at different ages, the patients with qSOFA score ≥ 1 were the most, and the proportion of sepsis patients was larger. Further analysis showed that qSOFA score ≥1 had a high diagnostic sensitivity in patients with suspected infection at different ages. In the youth group, the sensitivity was 84.4%, and the specificity was the highest (74.3%). Although qSOFA score ≥ 2 had a high specificity in the diagnosis of sepsis (all > 97%), its sensitivity was very low (all < 44%). In this study, all patients with a qSOFA score of 3 were sepsis, and the positive predictive value of the diagnosis of sepsis in each group was 100%. ROC curve analysis showed that the area under ROC curve (AUC) of qSOFA score for the diagnosis of sepsis in all suspected infection patients was 0.771 [95% confidence interval (95% CI) was 0.747-0.794], when the best cut-off value was 0.5, the sensitivity was 93.4% and the specificity was 45.6%. Among suspected infection patients of all ages, the accuracy of qSOFA score in the diagnosis of sepsis in the youth group and the longevity group was relatively high, with AUC (95% CI) of 0.825 (0.724-0.927) and 0.837 (0.756-0.917), respectively; when the best cut-off value was 0.5, the sensitivity was 84.4% or 92.2%, and the specificity was 74.3% or 56.4%, respectively. Conclusions:qSOFA score has an early diagnosis value for sepsis, especially in the patients aged < 45 years old or ≥ 90 years old. Using qSOFA score ≥2 to screen patients with suspected infection is likely to cause missed diagnosis.

Heterogeneous synthesis and electrochemical performance of LiMnPO4/C composites as cathode materials of lithium ion batteries.

In this study, a facile yet efficient interfacial hydrothermal process was successfully developed to fabricate LiMnPO4/C composites. In this strategy, the walls of carbon nanotubes were employed as heterogeneous nucleation interfaces and biomass of phytic acid (PA) as an eco-friendly phosphorus source. By comparing the experimental results, a reasonable nucleation-growth mechanism was proposed, suggesting the advantages of interfacial effects. Meanwhile, the as-synthesized LiMnPO4/C samples exhibited superior rate performances with discharge capacities reaching 161 mA h g-1 at C/20, 134 mA h g-1 at 1C, and 100 mA h g-1 at 5C. The composites also displayed excellent cycling stabilities by maintaining 95% of the initial capacity over 100 continuous cycles at 1C. Electrochemical impedance spectroscopy showed that the superior electrochemical performances were attributed to the low charge-transfer resistance and elevated diffusion coefficient of lithium ions. In sum, the proposed approach for the preparation of LiMnPO4/C composites looks promising for future production of composite electrode materials for high-performance lithium-ion batteries.

Value of pressure and respiratory rate in predicting success of weaning from mechanical ventilator in patients / 中华急诊医学杂志

Objective:To evaluate the performance of the combinative index-a product of pressure (P) and respiratory rate (RR), to predict the outcome of weaning.Methods:Single-center, case-control study method was used to prospectively collect the data of 76 patients who had been mechanically ventilated for at least 24 h in ICU of the Affiliated Changshu Hospital of Xuzhou Medical University from November 2017 to April 2019, excluding the patients with central respiration repression and primary neuromuscular disease. The spontaneous breath test (SBT) was performed for 1 h after the patient was ready to be weaned. All patients were divided into two groups according to whether they were successfully weaned from the mechanical ventilation: 50 cases in the success group and 26 cases in the failure group. Clinical data and values of peak inspiratory pressure (P peak), driving pressure (DP) and RR of two groups were collected. The independent sample t test and Mann-Whitney U test were used for the comparison between the two groups. The differences between enumeration data were assessed by Chi-square test. Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of each index. Results:Of the 76 patients studied, 26 patients failed extubation. The values of P peak×RR and DP×RR in the success group were significantly less than those in the failure group; P peak×RR (cmH 2O·breaths/min): 291.8±76.5 vs 519.8±108.8 ( P<0.01), DP×RR (cmH 2O·breaths/min): 131.6±34.2 vs 227.0±47.5 ( P<0.01). The AUC of P peak×RR, DP×RR was 0.960 and 0.941, respectively. A decrease in P peak×RR index less than 362 cmH 2O·breaths/min had a sensitivity of 96.2%, a specificity of 88.0%, a positive predictive value (PPV) of 97.8% and a negative predictive value (NPV) of 80.6%, to predict successful weaning. A decrease in DP×RR index less than 170 cmH 2O·breaths/min had a sensitivity of 88.5%, a specificity of 92.0%, a PPV of 94.0% and a NPV of 88.5%, to predict successful weaning. Conclusion:The combination of pressure and respiratory rate can accurately predict whether the patients can be successfully weaned from mechanical ventilation.

B lymphocytes expressing high levels of PD-L1 are key regulators of diabetes development in non-obese diabetic mice.

Programmed cell death 1 ligand 1 (PD-L1) plays a critical role in mediating autoimmune diseases, including type I diabetes (T1D). B cells are important antigen-presenting cells (APCs) that make a major contribution to T1D development. However, B cells expressing low levels of PD-L1 that infiltrate insulitic islets in NOD mice may not inhibit effector T cells and prevent T1D. Here, we generated PD-L1 transgenic NOD (NOD.PD-L1Tg) mice, in which most immune cells overexpress PD-L1, to investigate the ability of B cells overexpressing PD-L1 to inhibit diabetic CD4+ T cells and prevent T1D. The severity of insulitis in NOD.PD-L1Tg mice was significantly lower than in NOD mice and none developed diabetes. In addition, there were no differences in expression of activity markers by APCs following LPS stimulation between two groups. In vitro studies revealed that B cells expressing high levels of PD-L1 inhibited proliferation of and cytokine secretion by pre-diabetic CD4+ T cells, whereas in vivo studies showed that NOD/SCID mice receiving diabetic CD4+ T cells mixed with B cells overexpressing PD-L1 became diabetic at a slower rate. Thus, we propose that B cells showing high expression of PD-L1 protect NOD mice against T1D and downregulate diabetogenic CD4+ T cells.

Delta-secretase-cleaved Tau antagonizes TrkB neurotrophic signalings, mediating Alzheimer's disease pathologies.

BDNF, an essential trophic factor implicated in synaptic plasticity and neuronal survival, is reduced in Alzheimer's disease (AD). BDNF deficiency's association with Tau pathology in AD is well documented. However, the molecular mechanisms accounting for these events remain incompletely understood. Here we show that BDNF deprivation triggers Tau proteolytic cleavage by activating δ-secretase [i.e., asparagine endopeptidase (AEP)], and the resultant Tau N368 fragment binds TrkB receptors and blocks its neurotrophic signals, inducing neuronal cell death. Knockout of BDNF or TrkB receptors provokes δ-secretase activation via reducing T322 phosphorylation by Akt and subsequent Tau N368 cleavage, inducing AD-like pathology and cognitive dysfunction, which can be restored by expression of uncleavable Tau N255A/N368A mutant. Blocking the Tau N368-TrkB complex using Tau repeat-domain 1 peptide reverses this pathology. Thus, our findings support that BDNF reduction mediates Tau pathology via activating δ-secretase in AD.

Sphingosine 1-phosphate stimulates eyelid closure in the developing rat by stimulating EGFR signaling.

In many mammals, the eyelids migrate over the eye and fuse during embryogenesis to protect the cornea from damage during birth and early life. Loss-of-function mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway cause an eyes-open-at-birth (EOB) phenotype in rodents. We identified an insertional mutation in Spinster homolog 2 (Spns2) in a strain of transgenic rats exhibiting the EOB phenotype. Spns2, a sphingosine 1-phosphate (S1P) transporter that releases S1P from cells, was enriched at the tip of developing eyelids in wild-type rat embryos. Spns2 expression or treatment with S1P or any one of several EGFR ligands rescued the EOB Spns2 mutant phenotype in vivo and in tissue explants in vitro and rescued the formation of stress fibers in primary keratinocytes from mutants. S1P signaled through the receptors S1PR1, S1PR2, and S1PR3 to activate extracellular signal-regulated kinase (ERK) and EGFR-dependent mitogen-activated protein kinase kinase kinase 1 (MEKK1)-c-Jun signaling. S1P also induced the nuclear translocation of the transcription factor MAL in a manner dependent on EGFR signaling. MAL and c-Jun stimulated the expression of the microRNAs miR-21 and miR-222, both of which target the metalloprotease inhibitor TIMP3, thus promoting metalloprotease activity. The metalloproteases ADAM10 and ADAM17 stimulated EGFR signaling by cleaving a membrane-anchored form of EGF to release the ligand. Our results outline a network by which S1P transactivates EGFR signaling through a complex mechanism involving feedback between several intra- and extracellular molecules to promote eyelid fusion in the developing rat.

S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice.

Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO) and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl), was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs) into intermediate neural progenitors (INPs) in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment.

Clinical application value of template-assisted CT-guided radioactive seed implantation for pancreatic carcinoma / 中华放射学杂志

Objective To investigate the clinical value of coplanar template-assisted CT guided radioactive seeds implantation in the treatment of pancreatic carcinoma. Methods A total of 22 advanced pancreatic carcinoma patients underwent CT guided radioactive seeds implantation were retrospectively analyzed.Ten patients were treated with coplanar template-assisted with an average age of(65±10)years(48 to 77 years).Tweleve patients were treated without coplanar template assist with an average age of(68±13) years (47 to 84 years). The preoperative planning designs and postoperative dosimetry verifications were performed for all patients.The dose related parameters including D90,MPD,V100,V150and V200were compared between pre and post operation by t test. The operating time were also evaluated between the two groups. Results Overall the 22 patients were treated successfully without serious surgery-related complications. An average of 26 seeds were implanted in the coplanar template assisted implantation group,and 23 seeds were implanted in the non template-assisted implantation group. Preoperative V100in coplanar template group and non template group were(94.45 ± 1.32)% and(93.27 ± 1.37)% separately. Postoperative V100in both groups were(89.31 ± 2.58)% and(85.25 ± 4.35)% separately. Postoperative D90in both groups were (147.32±7.12)Gy and(149.25±4.86)Gy separately.Postoperative V150in both groups were(57.83±7.74)% and(63.97±7.75)% separately.Preoperative D90in both groups were(152.41±6.78)Gy and(153.30±7.79) Gy separately. Preoperative V150in both groups were(58.61 ± 14.11)% and(62.45 ± 6.49)% separately. Postoperative MPD in both groups were(87.64±10.60)Gy and(87.12±7.66)Gy separately.Postoperative V200in both groups were(34.12±7.67)%,(39.42±7.18)% separately.Preoperative MPD in both groups were (82.12±7.81)Gy and(83.43±4.86)Gy separately.Preoperative V200in both groups were(29.04±10.64)%, (36.11 ± 7.22)% separately. Compared with preoperative plans, the mean value of D90and V100decreased while the mean value of MPD and V200increased in postoperative verifications in both coplanar template assist CT guided radioactive seeds implantation group and non template-assisted group.However,there was no significant difference between pre and post operation except for V100(P<0.05). The operating time of coplanar template assist group and non template-assisted group were(44.3±12.4)min and(60.0±12.8)min respectively. The difference of operating time between two groups were statistically significant (P<0.05). Conclusion Compared with the treatment without template assist, coplanar template-assisted brachytherapy could be more accurate in preoperative plans optimization,and shorten the operation time and improve the patients'tolerance.

CT-guided radioactive 125I seeds implantation in treatment of spinal metastatic tumors / 中国介入影像与治疗学

Objective To evaluated the safety and clinical efficacy of CT-guided percutaneous radioactive 125I seeds implantation in treatment of spinal metastatic tumors.Methods Totally 20 cases (23 lesions) of spinal metastatic tumors with spinal compression and severe back pain were treated by CT-guided percutaneous 125I seeds implantation.Intractable pain and nerve function before and after therapy were evaluated.And the postoperative cumulative local tumors control rates and cumulative survival rates were calculated.Results The median follow-up period was 14 months (range 7-32months).There was no patient lost follow-up.And no severe complication occurred.Intractable pain significantly relieved one month after therapy.The neural retention rate of 12 patients with nerve function impairment was 85.00％ (17/20) and the neural function recovery rate was 30.00％ (6/20) three months after 125 I seeds'implantation.The local tumors control rates in 3-,6-,and 12-month were 100％,100％ and 90％,respectively.The survival rates in 6-and 12-month was 100％and 78.81％,respectively.Conclusion CT-guided percutaneous radioactive 125I seeds implantation for spinal metastatic tumors is safe and feasible.It can relief pain and improve neural function effectively.

Preliminary clinical study of biliary tract irradiation stent for hilar cholangiocarcinoma with malignant obstructive jaundice / 中国介入影像与治疗学

Objective To evaluate the efficacy and safety of biliary stent loaded with 125I seeds in treatment of hilar cholangiocarcinoma with malignant obstructive jaundice.Methods Totally 43 patients with malignant obstructive jaundice caused by cholangiocarcinoma were included.All the patients underwent percutaneous transhepatic puncture of the left and right side branch of the bile duct.In the hilar stenosis,the biliary stent with 125I seeds were implanted,and the biliary drainage tube had been kept in 3 to 5 days after procedures.The drainage tube was removed and the puncture road was closed after the patency of stents were confirmed by cholangiography.The changes of liver function before and after procedures were recorded,and the survival time was observed.Results Five biliary stents loaded with 125I seeds were implanted in type I (n=5),36 in type Ⅱ (n=18),8 in type Ⅲ (n=4) and 25 in type Ⅳ (n=16).The serum total bilirubin and direct bilirubin of patients before procedures were (145.54 ± 65.35) μmol/L and (124.73 ± 35.04) μmol/L,respectively,and (65.91±29.43)μmol/L and (35.50±15.12)μmol/L respectively after procedures.Compared with preoperative,the total bilirubin,direct bilirubin,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,C-reactive protein and gamma glutamic transaminase decreased significantly (all P＜0.05).The lactate dehydrogenase had no significant difference before and after operation (P=1.050).The median survival time was 13 months (3.0 to 22.5 months).The serious complications such as biliary puncture,pancreatitis,severe biliary tract infection or biliary bleeding were not occurred.Conclusion Biliary stent loaded with 125 I seeds is an effective therapy to alleviate symptoms of jaundice and prolong the survival time of patients with malignant obstructive jaundice caused by hilar cholangiocarcinoma.

Aescin reduces oxidative stress and provides neuroprotection in experimental traumatic spinal cord injury.

Aescin has many physiological functions that are highly relevant to spinal cord injury (SCI), including anti-inflammation, anti-oxidation, anti-oedema, and enhancing vascular tone. The present study investigated the putative therapeutic value of aescin in SCI, with a focus on its neuroprotective, anti-inflammatory, and anti-oxidative properties. Sodium aescinate (1.0mg/kg body weight) or equivalent volume of saline was administered 30min after injury by intravenous injection, with an additional dose daily for seven consecutive days after moderate SCI in rats. After contusion injury of the 8th thoracic (T8) spinal cord, aescin-treated rats developed less severe hind limb weakness than saline controls, as assayed by the Basso-Beattie-Bresnahan scale, the beam walking test, and a footprint analysis. The improved locomotor outcomes in aescin-treated rats corresponded to markedly decreased immune response, oxidative stress, neuronal loss, axon demyelination, spinal cord swelling, and cell apoptosis, measured around T8 after impact. Our data suggest aescin treatment as a novel, early, neuroprotective approach in SCI. Given the known safety of aescin in clinical applications, the results of this study suggest that it is a good candidate for SCI treatment in humans.

miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3ß pathway by targeting Rap2a.

A single microRNA (miRNA) can regulate expression of multiple proteins, and expression of an individual protein may be controlled by numerous miRNAs. This regulatory pattern strongly suggests that synergistic effects of miRNAs play critical roles in regulating biological processes. miR-9 and miR-124, two of the most abundant miRNAs in the mammalian nervous system, have important functions in neuronal development. In this study, we identified the small GTP-binding protein Rap2a as a common target of both miR-9 and miR-124. miR-9 and miR-124 together, but neither miRNA alone, strongly suppressed Rap2a, thereby promoting neuronal differentiation of neural stem cells (NSCs) and dendritic branching of differentiated neurons. Rap2a also diminished the dendritic complexity of mature neurons by decreasing the levels of pAKT and pGSK3ß. Our results reveal a novel pathway in which miR-9 and miR-124 synergistically repress expression of Rap2a to sustain homeostatic dendritic complexity during neuronal development and maturation.

Reactive astrocytes undergo M1 microglia/macrohpages-induced necroptosis in spinal cord injury.

BACKGROUND: A unique feature of the pathological change after spinal cord injury (SCI) is the progressive enlargement of lesion area, which usually results in cavity formation and is accompanied by reactive astrogliosis and chronic inflammation. Reactive astrocytes line the spinal cavity, walling off the lesion core from the normal spinal tissue, and are thought to play multiple important roles in SCI. The contribution of cell death, particularly the apoptosis of neurons and oligodendrocytes during the process of cavitation has been extensively studied. However, how reactive astrocytes are eliminated following SCI remains largely unclear. RESULTS: By immunohistochemistry, in vivo propidium iodide (PI)-labeling and electron microscopic examination, here we reported that in mice, reactive astrocytes died by receptor-interacting protein 3 and mixed lineage kinase domain-like protein (RIP3/MLKL) mediated necroptosis, rather than apoptosis or autophagy. Inhibiting receptor-interacting protein 1 (RIP1) or depleting RIP3 not only significantly attenuated astrocyte death but also rescued the neurotrophic function of astrocytes. The astrocytic expression of necroptotic markers followed the polarization of M1 microglia/macrophages after SCI. Depleting M1 microglia/macrophages or transplantation of M1 macrophages could significantly reduce or increase the necroptosis of astrocytes. Further, the inflammatory responsive genes Toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) are induced in necroptotic astrocytes. In vitro antagonizing MyD88 in astrocytes could significantly alleviate the M1 microglia/macrophages-induced cell death. Finally, our data showed that in human, necroptotic markers and TLR4/MyD88 were co-expressed in astrocytes of injured, but not normal spinal cord. CONCLUSION: Taken together, these results reveal that after SCI, reactive astrocytes undergo M1 microglia/macrophages-induced necroptosis, partially through TLR/MyD88 signaling, and suggest that inhibiting astrocytic necroptosis may be beneficial for preventing secondary SCI.

Aldose Reductase Regulates Microglia/Macrophages Polarization Through the cAMP Response Element-Binding Protein After Spinal Cord Injury in Mice.

Inflammatory reactions are the most critical pathological processes occurring after spinal cord injury (SCI). Activated microglia/macrophages have either detrimental or beneficial effects on neural regeneration based on their functional polarized M1/M2 subsets. However, the mechanism of microglia/macrophage polarization to M1/M2 at the injured spinal cord environment remains unknown. In this study, wild-type (WT) or aldose reductase (AR)-knockout (KO) mice were subjected to SCI by a spinal crush injury model. The expression pattern of AR, behavior tests for locomotor activity, and lesion size were assessed at between 4 h and 28 days after SCI. We found that the expression of AR is upregulated in microglia/macrophages after SCI in WT mice. In AR KO mice, SCI led to smaller injury lesion areas compared to WT. AR deficiency-induced microglia/macrophages induce the M2 rather than the M1 response and promote locomotion recovery after SCI in mice. In the in vitro experiments, microglia cell lines (N9 or BV2) were treated with the AR inhibitor (ARI) fidarestat. AR inhibition caused 4-hydroxynonenal (HNE) accumulation, which induced the phosphorylation of the cAMP response element-binding protein (CREB) to promote Arg1 expression. KG501, the specific inhibitor of phosphorylated CREB, could cancel the upregulation of Arg1 by ARI or HNE stimulation. Our results suggest that AR works as a switch which can regulate microglia by polarizing cells to either the M1 or the M2 phenotype under M1 stimulation based on its states of activity. We suggest that inhibiting AR may be a promising therapeutic method for SCI in the future.

Value of ultrasound-measured changes in diaphragmatic excursion in predicting successful weaning from mechanical ventilation during spontaneous breathing trial / 中华麻醉学杂志

Objective To evaluate the value of ultrasound-measured changes in diaphragmatic excursion (DE) in predicting successful weaning from mechanical ventilation during the spontaneous breathing trial (SBT).Methods Sixty-three patients of both sexes,who were mechanically ventilated for more than 24 h and screened for ascertained readiness to wean,aged 45-64 yr,were enrolled in the study.Bilateral DE was measured using ultrasound at 0,10 and 30 min of SBT.The patients who successfully completed 30 min of SBT were extubated.The patients were divided into either success group or failure group according to whether or not weaning was successful.Receiver operating characteristic (ROC) curves were used to evaluate the value of bilateral △DE30-10 in predicting successful weaning.Results There were 48 cases in success group and 15 cases in failure group.Bilateral △DE30-10 was significantly higher in failure group than in success group (P＜0.05).The area under the ROC curves of the right △DE30-10 in predicting successful weaning was 0.958,＜0.175 cm was used to predict successful weaning,and the sensitivity and specificity were 93.3％ and 87.5％,respectively.The area under the ROC curves of the left △DE30-10 in predicting successful weaning was 0.903,＜0.275 cm was used to predict successful weaning,and the sensitivity and specificity were 80.0％ and 89.6％,respectively.Conclusion The fight △DE30-10 measured using ultrasound can serve as an assistant index in predicting successful weaning from mechanical ventilation during SBT.

Loss of microRNA-124 expression in neurons in the peri-lesion area in mice with spinal cord injury.

MicroRNA-124 (miR-124) is abundantly expressed in neurons in the mammalian central nervous system, and plays critical roles in the regulation of gene expression during embryonic neurogenesis and postnatal neural differentiation. However, the expression profile of miR-124 after spinal cord injury and the underlying regulatory mechanisms are not well understood. In the present study, we examined the expression of miR-124 in mouse brain and spinal cord after spinal cord injury using in situ hybridization. Furthermore, the expression of miR-124 was examined with quantitative RT-PCR at 1, 3 and 7 days after spinal cord injury. The miR-124 expression in neurons at the site of injury was evaluated by in situ hybridization combined with NeuN immunohistochemical staining. The miR-124 was mainly expressed in neurons throughout the brain and spinal cord. The expression of miR-124 in neurons significantly decreased within 7 days after spinal cord injury. Some of the neurons in the peri-lesion area were NeuN(+)/miR-124(-). Moreover, the neurons distal to the peri-lesion site were NeuN(+)/miR-124(+). These findings indicate that miR-124 expression in neurons is reduced after spinal cord injury, and may reflect the severity of spinal cord injury.

Polarized Macrophages Have Distinct Roles in the Differentiation and Migration of Embryonic Spinal-cord-derived Neural Stem Cells After Grafting to Injured Sites of Spinal Cord.

Spinal cord injury (SCI) frequently provokes serious detrimental outcomes because neuronal regeneration is limited in the central nervous system (CNS). Thus, the creation of a permissive environment for transplantation therapy with neural stem/progenitor cells (NS/PCs) is a promising strategy to replace lost neuronal cells, promote repair, and stimulate functional plasticity after SCI. Macrophages are important SCI-associated inflammatory cells and a major source of secreted factors that modify the lesion milieu. Here, we used conditional medium (CM) from bone marrow-derived M1 or M2 polarized macrophages to culture murine NS/PCs. The NS/PCs showed enhanced astrocytic versus neuronal/oligodendrocytic differentiation in the presence of M1- versus M2-CM. Similarly, cotransplantation of NS/PCs with M1 and M2 macrophages into intact or injured murine spinal cord increased the number of engrafted NS/PC-derived astrocytes and neurons/oligodendrocytes, respectively. Furthermore, when cotransplantated with M2 macrophages, the NS/PC-derived neurons integrated into the local circuitry and enhanced locomotor recovery following SCI. Interesting, engrafted M1 macrophages promoted long-distance rostral migration of NS/PC-derived cells in a chemokine (C-X-C motif) receptor 4 (CXCR4)-dependent manner, while engrafted M2 macrophages resulted in limited cell migration of NS/PC-derived cells. Altogether, these findings suggest that the cotransplantation of NS/PCs together with polarized macrophages could constitute a promising therapeutic approach for SCI repair.

Electric signals regulate directional migration of ventral midbrain derived dopaminergic neural progenitor cells via Wnt/GSK3ß signaling.

Neural progenitor cell (NPC) replacement therapy is a promising treatment for neurodegenerative disorders including Parkinson's disease (PD). It requires a controlled directional migration and integration of NPCs, for example dopaminergic (DA) progenitor cells, into the damaged host brain tissue. There is, however, only limited understanding of how to regulate the directed migration of NPCs to the diseased or damaged brain tissues for repair and regeneration. The aims of this study are to explore the possibility of using a physiological level of electrical stimulation to regulate the directed migration of ventral midbrain NPCs (NPCs(vm)), and to investigate their potential regulation via GSK3ß and associated downstream effectors. We tested the effects of direct-current (DC) electric fields (EFs) on the migration behavior of the NPCs(vm). A DC EF induced directional cell migration toward the cathode, namely electrotaxis. Reversal of the EF polarity triggered a sharp reversal of the NPC(vm) electrotaxis. The electrotactic response was both time and EF voltage dependent. Pharmacologically inhibiting the canonical Wnt/GSK3ß pathway significantly reduced the electrotactic response of NPCs(vm), which is associated with the down-regulation of GSK3ß phosphorylation, ß-catenin activation and CLASP2 expression. This was further proved by RNA interference of GSK3ß, which also showed a significantly reduced electrotactic response in association with reduced ß-catenin activation and CLASP2 expression. In comparison, RNA interference of ß-catenin slightly reduced electrotactic response and CLASP2 expression. Both pharmacological inhibition of Wnt/GSK3ß and RNA interference of GSK3ß/ß-catenin clearly reduced the asymmetric redistribution of CLASP2 and its co-localization with α-tubulin. These results suggest that Wnt/GSK3ß signaling contributes to the electrotactic response of NPCs(vm) through the coordination of GSK3ß phosphorylation, ß-catenin activation, CLASP2 expression and asymmetric redistribution to the leading edge of the migrating cells.

Percutaneous intraductal radiofrequency ablation for the treatment of biliary stent stenosis：a preliminary study / 介入放射学杂志

Objective To evaluate the feasibility and effectiveness of percutaneous intraductal radiofrequency ablation (RFA) in treating biliary stent stenosis. Methods A total of 43 cases with biliary obstruction caused by biliary stent stenosis were enrolled in this study. Through percutaneous transhepatic pucturing of biliary duct, an EndoHPB catheter was placed in the stenotic site of the biliary stent, which was followed by RFA treatment. After RFA, biliary drainage catheter was reserved. The drainage catheter was removed when angiography confirmed that the stent was patent. Results Cholangiography showed that the biliary stent became patency after RFA in all patients. No procedure-related complications occurred. After RFA, the median patency time of the stenotic biliary stent in survival patients was 107 days (12-180 days). Conclusion The results of this preliminary clinical study indicate that percutaneous intraductal radiofrequency ablation has excellent effect and safety for the treatment of biliary stent stenosis, although more reliable and randomized controlled trials are needed before its effect and safety can be further proved.