Crocin Alleviates Intracerebral Hemorrhage-Induced Neuronal Ferroptosis by Facilitating Nrf2 Nuclear Translocation.

Intracerebral hemorrhage (ICH) is the deadliest type of stroke. Oxidative stress was considered to play an important role in ICH-induced secondary injury. Crocin, the main compound isolated from Crocus sativus L., possesses a potential anti-oxidative function in many types of diseases including ICH. In the current study, the protective role of crocin in ICH-induced brain injury was investigated in the ICH model. The ICH-induced brain edema and neurological deficits were analyzed by brain edema measurement and neurological testing. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity and the content of malondialdehyde (MDA) were assessed by a total superoxide dismutase assay kit. The expressions of ferroptosis-related genes were verified by quantitative real-time PCR (qPCR) and western blotting. The ICH-induced brain edema and neurological deficits were significantly decreased after treatment with crocin. Moreover, the SOD and GSH-px activities were obviously increased in the ICH with crocin-treated group compared with the ICH group, while the content of MDA was markedly decreased after treatment with crocin. Crocin inhibited ferroptosis of neuron cells, as evidenced by increased Fe2+ concentration and the expression of GPX4, FTH1, and SLC7A11. Mechanistically, crocin treatment increased the expression and nuclear translocation of Nrf2. Our data suggest that crocin alleviates intracerebral hemorrhage-induced neuronal ferroptosis by facilitating Nrf2 nuclear translocation.

Curcumin attenuates intracerebral hemorrhage-induced neuronal apoptosis and neuroinflammation by suppressing JAK1/STAT1 pathway.

Intracerebral hemorrhage (ICH) is a kind of fatal stroke with the highest mortality and morbidity in the world. To date, there is no effective treatment strategy for ICH. Curcumin, a major active ingredient of Curcuma longa L., possesses a potential anti-inflammatory activity in many types of disease. In the current study, the mechanism underlying curcumin attenuated ICH-induced neuronal apoptosis and neuroinflammation was explored. Herein, we studied that curcumin decreased brain edema and improved neurological function by using brain edema measurement, assessment of neurological-deficient score, immunofluorescence, and Western blotting analyses after ICH. The results showed that curcumin improved ICH-induced neuronal apoptosis and neuroinflammation. Functionally, the polarization of microglia was assessed by immunofluorescence and Western blotting analyses after ICH in the absence or presence of curcumin. The results suggested that the M1-type microglia were activated after ICH, while the effect was blocked by curcumin treatment, suggesting that curcumin alleviates the neuroinflammation and apoptosis of neurons by suppressing the M1-type polarization of microglia. Mechanically, M1 polarization of microglia was regulated by JAK1/STAT1, and the activation of JAK1/STAT1 was blocked by curcumin. Meanwhile, the protective function of curcumin can be blocked by RO8191, an activator of JAK1. Taken together, our study suggested that curcumin improved the ICH-induced brain injury through alleviating M1 polarization of microglia/macrophage and neuroinflammation via suppressing the JAK1/STAT1 pathway.

[Minimally invasive external fixation of humeral supracondylar angular rotation center for the treatment of cubitus varus deformity in adolescents].

OBJECTIVE: To investigate clinical effect of minimally invasive osteotomy and external fixation with the center of roration of angulation (CORA) in treating cubitus varus in adolescents. METHODS: From August 2013 to August 2017, 15 patients with cubitus varus caused by supracondylar fracture of humerus were treated with minimally invasive osteotomy and external fixation with the CORA. Among them, including 9 males and 6 females; 11 patients on the left side and 4 patients on the right side; aged from 13 to 16 years old with an average of 14.5 years old. The time from injury to operation was for 6 to 10 years with an average of 7.5 years. Five patients had a history of recurrence after cubitus varus surgery. Correction time. fracture healing time, carrying angle were observed, Laupattarakasem standard was used to evaluate clinical effect. RESULTS: All patients were followed up from 12 to 30 months with an average of 24 months; correction time ranged from 3 to 5 weeks with an average of 4 weeks; fracture healing time ranged from 4 to 6 months with an average of 5 months; carrying angle before operation ranged from -12° to -23°, and improved 9° to 14° after operation. According to Laupattarakasem evaluation criteria, 11 patients got an excellent result, 3 good and 1 fair. CONCLUSIONS: Minimally invasive osteotomy and external fixation with CORA in treating cubitus varus deformity in adolescents has advantages of less trauma, less blood loss, earlier exercise, speed and angle of correction could controlled without hospitalized for fixation.

Early increase of neutrophil-to-lymphocyte ratio predicts 30-day mortality in patients with spontaneous intracerebral hemorrhage.

AIMS: To examine whether early rise of neutrophil-to-lymphocyte ratio (NLR) after patient hospitalization correlates with 30-day mortality in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: This retrospective study included all patients receiving treatment for spontaneous ICH between January 2015 and September 2016 at the Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences in Shanghai, China. NLR was determined at admission (T1), at 24-48 hours (T2) and 5-7 days (T3). NLR and clinicopathologic features were compared between those who survived for >30 days vs not. Multivariate regression was used to identify risk factors for 30-day mortality. RESULTS: A total of 275 subjects were included in the analysis: 235 survived for at least 30 days; the remaining 40 subjects died within 30 days. The patients who died within 30 days had higher ICH score, larger ICH volume, and lower GCS score (all P < 0.05). In comparison with the baseline (NLRT1 ), NLR at 24-48 hours (NLRT2 ) and 5-7 days (NLRT3 ) was significantly higher in patients who died within 30 days (P < 0.05), but not in patients surviving for >30 days. In the multivariate analysis, the 30-day mortality was associated with both NLRT2 (OR 1.112, 95%CI 1.032-1.199, P = 0.006) and NLRT3 (OR 1.163, 95%CI 1.067-1.268, P = 0.001). Spearman correlation analysis showed that both NLRT2 and NLRT3 correlated inversely with GCS score and positively with ICH score and ICH volume at the baseline. CONCLUSIONS: Early rise of NLR predicts 30-day mortality in patients with spontaneous ICH.

Serum iron levels are an independent predictor of in-hospital mortality of critically ill patients: a retrospective, single-institution study.

OBJECTIVE: This study aimed to examine the relationship between serum iron levels and in-hospital mortality in critically ill patients. METHODS: We retrospectively studied 250 critically ill patients who received treatment at the intensive care unit between June 2015 and May 2017. Blood chemistry and hepatic and renal function were measured. Kaplan-Meier survival curves were plotted according to serum iron levels. Correlations between serum iron levels and other variables were analyzed. RESULTS: A total of 165 (66.0%) patients had abnormally low serum iron levels (<10.6 µmol/L). Patients who died during hospitalization had markedly higher Acute Physiology and Chronic Health Evaluation II scores and significantly lower serum iron levels compared with those who survived. Cumulative survival was significantly lower in patients with low serum iron levels than in those with normal serum iron levels in subgroup analysis of older patients (n = 192). Multivariate regression analysis showed that, after adjusting for relevant factors, low serum iron levels remained an independent risk for in-hospital mortality (odds ratio 2.014; 95% confidence interval 1.089, 3.725). CONCLUSIONS: Low serum iron levels are present in a significant proportion of critically ill patients and are associated with higher in-hospital mortality, particularly in older patients.

Neutrophil-to-Lymphocyte Ratio Is an Independent Predictor of 30-Day Mortality of Intracerebral Hemorrhage Patients: a Validation Cohort Study.

In a previous study in patients with intracranial hemorrhage (ICH), we found an association between high neutrophil-to-lymphocyte ratio (NLR) with poor short-term mortality. In the current study, this preliminary finding was validated using an independent patient cohort. A total of 181 ICH patients (from January 2016 to December 2017) were included. Diagnosis was confirmed using computed tomography (CT) in all cases. Patient survival (up to 30 days) was compared between subjects with high NLR (above the 7.35 cutoff; n = 74) versus low NLR (≤ 7.35; n = 107) using Kaplan-Meier analysis. A multivariate logistic regression was performed to identify factors that influenced the 30-day mortality. Correlation between NLR with other relevant factors (e.g., C-reactive protein (CRP) and fibrinogen) was examined using Spearman correlation analysis. The 30-day mortality was 19.3% (35/181) in the entire sample, 37.8% (28/74) in the high-NLR group, and 6.5% (7/107) in the low-NLR group (P < 0.001). In comparison to the low-NLR group, the high-NLR group had higher rate of intraventricular hemorrhage (29.7 vs. 16.8%), ICH volume (median 23.9 vs. 6.0 cm3) and ICH score (median 1.5 vs. 0), and lower GCS score (9.4 ± 4.5 vs. 12.9 ± 3.2). An analysis that divided the samples into three equal parts based on NLR also showed increasing 30-day mortality with incremental NLR (1.6, 15.0, and 41.7% from lowest to highest NLR tertile, P for trend < 0.001). Kaplan-Meier curve showed higher 30-day mortality in subjects with high NLR than those with low NLR (P < 0.001 vs. low-NLR group, log-rank test). High NLR (> 7.35) is associated with poor short-term survival in acute ICH patients.

Dynamic Change of Red Cell Distribution Width Levels in Prediction of Hospital Mortality in Chinese Elderly Patients with Septic Shock.

BACKGROUND: The normal range of red cell distribution width (RDW) level is <15%. Several studies have indicated that a high RDW level was associated with mortality in critically ill patients, and the patients with a high RDW level need increased focus in clinical practice. In view of the difficulty in defining the specific value of high RDW level, the key is to focus on the patient with the level beyond the normal upper limit. This study aimed to determine whether dynamic change of RDW levels, rather than the level itself, is predictive of death in elderly patients with septic shock when RDW level is beyond 15%. METHODS: Between September 2013 and September 2015, the elderly septic shock patients with RDW level beyond 15% were enrolled in this study. The RDW levels were measured at enrollment (day 1), and days 4 and 7 after enrollment. Sequential Organ Failure Assessment (SOFA) scores were recorded simultaneously. RESULTS: A total of 45 patients, including 32 males and 13 females, were included in the final analysis. Based on their hospital outcomes, these patients were divided into the survivor group (n = 26) and the nonsurvivor group (n = 19). There were no significant differences in age, gender, body mass index, initial level of RDW, Acute Physiology and Chronic Health Evaluation II scores, and SOFA scores between survivors and nonsurvivors. At days 4 and 7 measurement, both RDW level (median [interquartile range]: day 4: 15.8 [2.0]% vs. 16.7 [2.0]%, P= 0.011; and day 7: 15.6 [1.8]% vs. 17.7 [2.5]%, P= 0.001) and SOFA scores (day 4: 7.0 [4.0] vs. 16.0 [5.0], P< 0.001, day 7: 5.5 [4.0] vs. 17.0 [5.0], P< 0.001) were significantly lower in survivors than those in nonsurvivors. Dynamic changes of RDW and SOFA scores in survivor group were significantly different from those in nonsurvivor group (all P< 0.05). Continuous increase in RDW level was observed in 10 of the 13 nonsurvivors, but only in 3 of the 26 survivors. The level of RDW7 and dynamic changes significantly correlated with their counterparts of SOFA scores (all P< 0.05), whereas the levels of RDW1 and RDW4 had no significant correlation with their counterparts of SOFA scores (all P> 0.05). CONCLUSIONS: Continuous increase in RDW level, rather than the level of RDW itself, was more useful in predicting hospital death in elderly patients with septic shock when the level of RDW was >15%. The dynamic changes of RDW were highly correlated with the SOFA score in the patients.

A new benzofuran derivative from Nicotiana tabacum.

A new benzofuran derivative, methyl 3-acetyl-7-hydroxy-6-methoxy-2-methylbenzofuran-4-carboxylate (1), and a known compound pyrrolezanthine (2), were isolated from leaves of Nicotiana tabacum. Compound 1 was elucidated by means of spectroscopic methods, as well as X-ray diffraction. Both compounds 1 and 2 exhibited moderate inhibitory activities on human cancer cell lines.

[Repairing tibial post-traumatic osteomyelitis with bone and skin defect by Ilizarov technique at stage I].

OBJECTIVE: To explore clinical effects of Ilizarov technique at stage I for repairing tibial post-traumatic osteomyelitis with bone and skin defect. METHODS: From June 2010 to December 2013,44 patients with tibial post-traumatic osteomyelitis with bone and skin defect were treated with Ilizarov technique at stage I . Among them, there were 35 males and 9 females aged from 18 to 70 years old with an average of 42.5 years old. Bone defect ranged from 4 to 16 cm, skin defect ranged from 3 cm x 4 cm to 5 cm x 16 cm. The operation was performed debridement thoroughly, removed inflammatory bone section, osteotomy invasively, install circular external fixator by Ilizarow technique; screw nut were rotated at 1 week after operation, and prolonged 0.5 to 1.0 mm everyday. Wound surface, new born callus and bone healing were observed to evaluate clinical effects. RESULTS: All patients were followed up from 11 to 36 months with an average of 18.5 months. Bone defect after osteotomy was from 6 to 22 cm with an average of 11.5 cm; the time of wound healing time ranged from 21 to 79 d with an average of 38 d; bone defect healing time was from 8 to 15 months with an average of 12.5 months. All patients were cured, no recurrent infection, refracture and shorten of calf deformity were occurred. CONCLUSION: Repairing tibial post-traumatic osteomyelitis with bone and skin defect by llizarov technique at stage I has advantages of less trauma, low inflammatory recurrence rate, could avoid multiple complex operation, and receive definite curative effect.

Diterpenoids and Limonoids from the Leaves and Twigs of Swietenia mahagoni.

Three new compounds, including two diterpenoids, nemoralisins H and I (1 and 2), and a limonoid, 2-methoxy khayseneganin E (3), along with four known constituents (4-7), were isolated from the leaves and twigs of Swietenia mahagoni. Their chemical structures were elucidated by means of spectroscopic analysis. The cytotoxities of these isolated constituents were assayed.

Protein-imprinted polymer with immobilized assistant recognition polymer chains.

Here we introduce a new method for preparing a protein-imprinted polymer with immobilized assistant recognition polymer chains as an additional element of monomer to create effective recognition sites. In this work the bovine serum albumin was used as template and the template protein was selectively assembled with immobilized assistant recognition polymer chains from their library, numerous limited length polymer chains with randomly distributed recognition sites and immobilizing sites. These assemblies of protein and immobilized assistant recognition polymer chains would be adsorbed by the macro porous adsorbent spheres and immobilized by cross-linking polymerization. After removing the template, binding sites that were complementary to the target protein in size, shape and position of recognition groups were exposed, and their confirmation was preserved by the cross-linked structure. The synthesized imprinted polymer was used to adsorb BSA from protein mixtures, and showed a high selectivity.