BACKGROUNDPulmonary embolism (PE) can be difficult to diagnose in elderly patients because of the coexistent diseases and the combination of drugs that they have taken. We aimed to compare the clinical diagnostic values of the Wells score, the revised Geneva score and each of them combined with D-dimer for suspected PE in elderly patients.

METHODSThree hundred and thirty-six patients who were admitted for suspected PE were enrolled retrospectively and divided into two groups based on age (≥65 or <65 years old). The Wells and revised Geneva scores were applied to evaluate the clinical probability of PE, and the positive predictive values of both scores were calculated using computed tomography pulmonary arteriography as a gold standard; overall accuracy was evaluated by the area under the curve (AUC) of receiver operator characteristic curve; the negative predictive values of D-dimer, the Wells score combined with D-dimer, and the revised Geneva score combined with D-dimer were calculated.

RESULTSNinety-six cases (28.6%) were definitely diagnosed as PE among 336 cases, among them 56 cases (58.3%) were ≥65 years old. The positive predictive values of Wells and revised Geneva scores were 65.8% and 32.4%, respectively (P < 0.05) in the elderly patients; the AUC for the Wells score and the revised Geneva score in elderly was 0.682 (95% confidence interval [CI]: 0.612-0.746) and 0.655 (95% CI: 0.584-0.722), respectively (P = 0.389). The negative predictive values of D-dimer, the Wells score combined with D-dimer, and the revised Geneva score combined with D-dimer were 93.7%, 100%, and 100% in the elderly, respectively.

CONCLUSIONSThe diagnostic value of the Wells score was higher than the revised Geneva score for the elderly cases with suspected PE. The combination of either the Wells score or the revised Geneva score with a normal D-dimer concentration is a safe strategy to rule out PE.

Aged ; Aged, 80 and over ; Angiography ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Humans ; Male ; Pulmonary Embolism ; diagnosis ; diagnostic imaging ; metabolism ; Retrospective Studies

Objective To observe the effects of mild hypothermia on the heat shock protein 70 (HSP70), interlukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in blood and cerebrospinal fluid in patients with cerebroma and explore the molecular mechanism of hypothermia on cerebral ischemia. Methods Forty patients, selected for cerebroma resection under microscopy, were randomized innormothermia group (n=20, 36.6±0.4 ℃) and hypothermia group (n=20,34.8±0.6 ℃). These temperatures were guaranteed by air temperature control blanket. Jugular venous blood and cerebrospinal fluid were collected before the anesthesia induction (T1), 1 h after opening the endocranium (T2) and 24 h after the operation (T3). The content of HSP70, IL-6 and TNF-α in the blood and cerebrospinal fluid was measured by ELISA, and the results were statically analyzed. Results The core temperature in the hypothermia group was decreased significantly from starting the operation to the end of tumor resection as compared with that in the normothermia group (P<0.05). The level of HSP70 in blood or cerebrolspinal fluid presented an increasing trend in both groups, and the level of HSP70 at T2 and T3 in the hypothermia group was significantly higher than that in the normothermia group (P<0.05). Compared with those in the normothermia group, the levels of IL-6 and TNF-α in blood or cerebrospinal fluid at T2 and T3 in the hypothermia group were significantly lower (P<0.05). At T1 and T2 in the normothermia group, the content of HSP70 in cerebrospinal fluid was obviously higher than that in blood (P<0.05).Conclusion Mild hypothermia can increase the expression level of HSP70 in blood and cerebrospinal fluid and decrease the level of IL-6 and TNF-α in blood and cerebrospinal fluid. HSP70 in cerebrospinal fluid might be more sensitive than that in blood in presenting the brain injury.

OBJECTIVESTo study the effects of Sanqi qisodium hyaluronate gel on collagen-I and collagen-III expression in the process of rabbits' epidural scar formation after operation.

METHODSNinety-six white rabbits with 6-month-old, half males and half females, weighted from 2 to 2.5 kg, which were randomly divided into normal saline group (A), Sanqi group (B), qisodium hyaluronate group (C) and Sanqi qisodium hyaluronate gel group (D). The laminectomy of rabbits were performed in group A, B, C, D, the duras were surrounded with normal saline, Sanqi liquid, qisodium hyaluronate and Sanqi qisodium hyaluronate gel respectively. Animals of each group were killed at 1, 2, 4, 8 weeks after operation. Use Masson staining for histological observation of collagen, and in situ hybridization staining for the analysis of collagen-I and collagen-III expression.

RESULTSIn the Masson staining, Sanqi qisodium hyaluronate gel group was more regular than the control group in the shape of collagen texture. As to the expression of collagen-I, and Sanqi qisodium hyaluronate gel group was lower than normal saline group, the Sanqi group and qisodium hyaluronate group at 4 weeks after using medicine (P < 0.01); while the Sanqi qisodium hyaluronate gel group was higher than normal saline group, Sanqi group and qisodium hyaluronate group in the collagen-III expression (P < 0.01).

CONCLUSIONSSanqi qisodium hyaluronate gel could improve collagen's arrangement of the rabbit's epidural scar after operation, reduce its rigidity and increase flexibility.

Animals ; Cicatrix ; etiology ; metabolism ; Collagen Type I ; genetics ; metabolism ; Collagen Type III ; genetics ; metabolism ; Epidural Space ; Female ; Gels ; Gene Expression Regulation ; drug effects ; Hyaluronic Acid ; chemistry ; Laminectomy ; adverse effects ; Male ; RNA, Messenger ; genetics ; metabolism ; Rabbits

OBJECTIVETo investigate the effects and mechanism of qi-tonifying and stasis-eliminating (QTSE) therapy on the expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in the brains of intracerebral hemorrhagic (model) rats.

METHODSOne hundred and eighty Sprague-Dawley rats were randomly divided into six groups: the normal group (n=5), the sham-operative (SO) group (n=35), the model group (n=35), the QTSE group (n=35), the QT group (n=35) and the SE group (n=35). All the rats except those in the normal group and SO group were established into an intracerebral hemorrhage(ICH) model by intracerebral injection of collagenase type VII and the latter three were orally administered with Buyang Huanwu Decoction (a classical recipe for QTSE) or with some of its components for qi-tonification and for stasis-elimination, respectively. To the other three groups, normal saline solutions were given instead. Behavioral tests were carried out in the animals randomly chosen from each group on days 1, 2, 4, 7, 14, 21 and 28 after modeling. The expressions of VEGF, Flk-1 and Flt-1 were determined by immunohistochemistry and the number of vascular segments with positive expression in the injured brain area of the rats was calculated.

RESULTSFrom day 7 onwards, the asymmetric forelimb use rate in the QTSE group recovered more significantly than that in the other model groups. In the model group, the expressions of VEGF, Flk-1 and Flt-1 appeared on day 1 and reached a peak on day 21, then weakened gradually. In the QTSE group, as compared with the other model groups, a higher level of VEGF expression was shown from day 7 (P<0.01) and a higher level of Flt-1 expression was shown from the 7th day to the 21st day (P<0.01).

CONCLUSIONQTSE therapy can up-regulate the expressions of VEGF and its receptors (Flk-1 and Flt-1) and improve the recovery of kinetic function in the ICH rats, which may be correlated with its action in modulating vascular regeneration to promote the reconstruction of microvascular networks in the damaged areas.

Animals ; Behavior, Animal ; drug effects ; Brain ; drug effects ; metabolism ; Cerebral Hemorrhage ; drug therapy ; metabolism ; Female ; Forelimb ; physiopathology ; Male ; Medicine, Chinese Traditional ; methods ; Phytotherapy ; methods ; Qi ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

Background/Aims: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Methods: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. Results: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. Conclusions LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. Conclusions Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

Objective To evaluate the effectiveness of intensive lifestyle intervention on rural residents with metabolic syndrome (MS) . Methods A total of 253 patients with MS selected from cross-sectional survey were divided into intensive lifestyle intervention and conventional management group incomplete randomly. Aimed to control weight, patients in the intervention group were treated with dietary control and exercise guidance. Besides, their compliances were assessed. In conventional management group, patients were disposed according to chronic disease management specification. Anthropometric measurements and biochemical markers detection were carried out in both groups at baseline and at the end of 6 months. Results These main anthropometric measurements and biochemical markers have no significant difference between the intervention group and conventional management group at the baseline (P>0.05) . After 6 months intensive lifestyle modification, the prevalence of MS did not significantly differ between the two groups: it was 67.14% in the intervention group and 60.95% in the conventional management group (P>0.05) .In the intervention group, the body weight, BMI and the waist circumference were decreased by 3.11 kg, 1.50 kg/m2, 4.29 cm, respectively, and 1.23 kg, 0.47 kg/m2, 1.22 cm in the conventional management group. The changes were significantly larger in the intervention group than in the conventional management group (P<0.01) .Uric acid, triglyceride were decreased by 14.30 μmol/L, 0.01 mmol/L, respectively, in the intervention group and in the conventional management group they were increased by 18.17 μmol/L and 0.41 mmol/L conversely. While the high density lipoprotein cholesterol was increased by 0.02 mmol/L, it was decreased by 0.10 mmol/L in the conventional management group (P<0.01) . Body weight and BMI decreased by 3.93kg and 1.40 kg/m2 in the high compliance group, compared to low compliance group, there was statistically difference with regard to this change between the two groups (P<0.05) . While the body fat% was decreased by 2.27%, and it was increased by 1.01% in the conventional management group (P<0.05) . Conclusion For rural residents, the beneficial effects of intensive lifestyle intervention are improving metabolic risk factors. The compliance is the main factor of the effects of intervention.

OBJECTIVE: To evaluate the value of conventional and age-adjusted D-dimer cut-off value combined with 2-level Wells score for diagnosis of suspected pulmonary embolism. METHODS: In the study, 335 patients with suspected pulmonary embolism who visited Peking University People's Hospital were enrolled retrospectively, then 274 patients with age over fifty years were chosen. The 2-level Wells score was applied to evaluate the clinical probability of pulmonary embolism, the diagnostic value of traditional D-dimer cut-off value (500 μg/L) and age adjusted D-dimer cut-off value (age×10 μg/L above 50 years) combined with Wells score no greater than 4 were compared. Computed tomography pulmonary arteriography (CTPA) was considered as the gold standard for diagnosis of pulmonary embolism. RESULTS: (1) The area under a receiver operating characteristic (ROC) curve (AUC) in analysis of the combination of Wells score no greater than 4 and traditional D-dimer cut-off value was 0.764 (95%CI: 0.703-0.818). On the other hand, the AUC in a ROC analysis of the combination of Wells Score no greater than 4 and age-adjusted D-dimer cut-off value was 0.814 (95%CI:0.756-0.863). These two results did not differ statistically (Z=0.05, P=0.121). (2) The sensitivity, specificity, positive predictive value, negative predictive value and Youden index of the diagnosis of pulmonary embolism of the combination of traditional D-dimer cut-off value and 2-level Wells Score were 100%, 48.9%, 28.8%, 100%, and 0.49, respectively. Meanwhile, the sensitivity, specificity, positive predictive value, negative predictive value and Youden index of the diagnosis of pulmonary embolism of the combination of age-adjusted D-dimer cut-off value and 2-level Wells Score were 97.4%, 62.3%, 35.5%, 99.1%, and 0.60, respectively. Compared with using traditional D-dimer cut-off value, using age-adjusted D-dimer cut-off value could improve the diagnosis specificity (traditional D-dimer cut-off value group: 48.9%, age-adjusted D-dimer cut-off value group: 62.3%) of pulmonary embolism without reducing the sensitivity (traditional D-dimer cut-off value group: 100%, age-adjusted D-dimer cut-off value group: 99.1%). (3) Among the 222 patients with Wells Score no greater than 4, 90 patients were with D-dimer less than traditional cut-off value (500 μg/L), and 25 patients (account for 11.3% of all 222 patients) were with D-dimer between traditional cut-off value and age-adjusted cut-off value. CONCLUSION The application of age-adjusted D-dimer cut-off value can improve the diagnostic specificity of pulmonary embolism in patients over 50 years, without reducing the sensitivity. It can be used for ruling out suspected pulmonary embolism safely.
Fibrin Fibrinogen Degradation Products/analysis* ; Humans ; Predictive Value of Tests ; Pulmonary Embolism/diagnosis* ; Retrospective Studies ; Sensitivity and Specificity

OBJECTIVE: Exercise, as a common non-drug intervention, is one of several lifestyle choices known to reduce the risk of cancer. Mitochondrial division has been reported to play a key role in the occurrence and transformation of hepatocellular carcinoma (HCC). This study investigated whether exercise could regulate the occurrence and development of HCC through mitosis. METHODS: Bioinformatics technology was used to analyze the expression level of dynamin-related protein 1 (DRP1), a key protein of mitochondrial division. The effects of DRP1 and DRP1 inhibitor (mdivi-1) on the proliferation and migration of liver cancer cells BEL-7402 were observed using cell counting kit-8, plate colony formation, transwell cell migration, and scratch experiments. Enzyme-linked immunosorbent assay, Western blot and real-time polymerase chain reaction were used to detect the expression of DRP1 and its downstream phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. A treadmill exercise intervention was tested in a nude mouse human liver cancer subcutaneous tumor model expressing different levels of DRP1. The size and weight of subcutaneous tumors in mice were detected before and after exercise. RESULTS: The expression of DRP1 in liver cancer tissues was significantly upregulated compared with normal liver tissues (P < 0.001). The proliferation rate and the migration of BEL-7402 cells in the DRP1 over-expression group were higher than that in the control group. The mdivi-1 group showed an inhibitory effect on the proliferation and migration of BEL-7402 cells at 50 μmol/L. Aerobic exercise was able to inhibit the expression of DRP1 and decrease the size and weight of subcutaneous tumors. Moreover, the expression of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) decreased in the exercise group. However, exercise could not change p-PI3K and p-AKT levels after knocking down DRP1 or using mdivi-1 on subcutaneous tumor. CONCLUSION Aerobic exercise can suppress the development of tumors partially by regulating DRP1 through PI3K/AKT pathway.
Animals ; Apoptosis ; Carcinoma, Hepatocellular/therapy* ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Dynamins ; Liver Neoplasms/therapy* ; Mice ; Phosphatidylinositol 3-Kinase/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction

The breakthrough progress of implantable brain-computer interfaces (iBCIs) technology in the field of clinical trials has attracted widespread attention from both academia and industry. The development and advancement of this technology have provided new solutions for the rehabilitation of patients with movement disorders. However, challenges from many aspects make it difficult for iBCIs to further implement and transform technologies. This paper illustrates the key challenges restricting the large-scale development of iBCIs from the perspective of system implementation, then discusses the latest clinical application progress in depth, aiming to provide new ideas for researchers. For the system implementation part, we have elaborated the front-end signal collector, signal processing and decoder, then the effector. The most important part of the front-end module is the neural electrode, which can be divided into two types: piercing and attached. These two types of electrodes are newly classified and described. In the signal processing and decoder section, we have discussed the experimental paradigm together with signal processing and decoder for the first time and believed that the experimental paradigm acts as a learning benchmark for decoders that play a pivotal role in iBCIs systems. In addition, the characteristics and roles of the effectors commonly used in iBCIs systems, including cursors and robotic arms, are analyzed in detail. In the clinical progress section, we have divided the latest clinical progress into two categories: functional rehabilitation and functional replacement from the perspective of the application scenarios of iBCIs. Functional rehabilitation and functional replacement are two different types of application, though the boundary between the two is not absolute. To this end, we have first introduced the corresponding clinical trial progress from the three levels: application field, research team, and clinical timeline, and then conducted an in-depth discussion and analysis of their functional boundaries, in order to provide guidance for future research. Finally, this paper mentions that the key technical challenges in the development of iBCIs technology come from multiple aspects. First of all, from the signal acquisition level, high-throughput and highly bio-compatible neural interface designing is essential to ensure long-term stable signal acquisition. The electrode surface modification method and electrode packaging were discussed. Secondly, in terms of decoding performance, real-time, accurate, and robust algorithms have a decisive impact on improving the reliability of iBCIs systems. The third key technology is from the perspective of practicality, we believe that the signal transmission mode of wireless communication is the trend of the future, but it still needs to overcome challenges such as data transmission rate and battery life. Finally, we believe that issues such as ethics, privacy, and security need to be addressed through legal, policy, and technological innovation. In summary, the development of iBCIs technology requires not only the unremitting efforts of scientific researchers, but also the participation and support of policymakers, medical professionals, technology developers, and all sectors of society. Through interdisciplinary collaboration and innovation, iBCIs technology will achieve wider clinical applications in the future and make important contributions to improving the quality of life of patients.