Nimbolide targeting SIRT1 mitigates intervertebral disc degeneration by reprogramming cholesterol metabolism and inhibiting inflammatory signaling

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

Analyses of diagnosis and treatment of foreign body aspiration in children with tracheobronchial variations / 中华耳鼻咽喉头颈外科杂志

Objective@#To investigate the key issues in the diagnosis and treatment of foreign body aspiration in children with tracheobronchial variations.@*Methods@#A retrospective study was performed for 11 pediatric patients who were treated in Department of Otorhinolaryngology and Head and Neck Surgery, Henan Province People′s Hospital after a diagnosis of foreign body aspiration with tracheobronchial variations between January 2015 and December 2017. There were 7 males and 4 females among the 11 cases of foreign body aspiration with tracheobronchial variations, ranging between 9 months and 11 years of age.@*Results@#Among 11 cases, the types of variationswere tracheal bronchus in 9 cases, bridging bronchus in 1 case and simple tracheal stenosis in 1 case. All of the pediatric patients were under general anesthesia, and the foreign bodies were removed by bronchoscopy successfully with no significant complications.@*Conclusions@#The possibility of tracheobronchial variations should be considered in children with recurrent wheezing and poor efficacy of regular treatment before foreign body aspiration. Removal of foreign body via rigid bronchoscope under general anesthesia is a safe and effective treatment. These children are needed to combine the situation oftracheobronchial variations and the location of foreign bodies to guide the operation, and strengthened the perioperative treatment.

A comparison of Streptococcus agalactiae septic arthritis and non-Streptococcus agalactiae septic arthritis

<p><b>INTRODUCTION</b>Streptococcus agalactiae (Group B Streptococcus, GBS) is an uncommon cause of septic arthritis in the adult population. In recent years, there has been an increase in the incidence of GBS septic arthritis. This study aims to compare the clinical presentation, investigations, microbiology and outcome of management in patients with GBS and non-GBS septic arthritis.</p><p><b>METHODS</b>Retrospective review of hospital surgical records was done to identify all patients treated surgically at our institution from January 2011 to January 2016 for primary septic arthritis. Patients were categorised into two groups: those with culture-proven GBS septic arthritis and those with causative pathogens that were not GBS. Patients who were medically unfit for surgical intervention as well as those who declined interventional procedures were excluded from the study.</p><p><b>RESULTS</b>A total of 83 patients were included in the study: 62 (74.7%) had non-GBS septic arthritis and 21 (25.3%) had GBS septic arthritis. Patients with GBS septic arthritis were more likely to have polyarticular involvement (p < 0.001) and involvement of less common sites such as the elbow joint. They were also more likely to have elevated inflammatory markers (C-reactive protein > 150 mg/L; p = 0.017) and positive blood cultures (p = 0.02), and were typically healthy adults with no medical comorbidities (p = 0.012).</p><p><b>CONCLUSION</b>Patients with GBS septic arthritis were more likely to present with polyarticular involvement, positive blood cultures and higher levels of C-reactive protein on admission, and tended to be healthier individuals with no medical comorbidities.</p>

Analysis on the myocardial enzyme spectrum of mountain yaks, alien mountain yellow cattle and low altitude yellow cattle in Qinghai Plateau / 中国生化药物杂志

Objective To compare the myocardial enzyme spectrum of native mountain yaks ( Bos grunniens) , alien mountain yellow cattle ( Bos taurus domestica) and low altitude yellow cattle breeding in Qinghai plateau, explove the mechanism that the native mountain yaks adapt to the plateau environment.Methods The samples were treated by cervical bleeding to death, and whole blood was collected.Then serum were prepared from whole blood.The myocardial enzymes including aspartate amino transferase, creatine kinase, creatinine kinase-MB isoenzyme, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and.Results In the native mountain yaks and in the alien mountain yellow cattle, levels of AST, CK, CK-MB were significantly higher than those in the low altitude yellow cattle (P<0.05);compared with the alien mountain yellow cattle, levels of AST,CK were significantly higher than those in the native mountain yaks (P<0.05),CK-MB,LDH and HBDH were lower(P<0.05).The results suggested that under the high altitude and hypoxia environment, myocardial cell injury occurred in the alien mountain yellow cattle, thus various enzymes penetrated through the cells into the blood circulation, lead to the higher serum enzymatic levels.Conclusion The phenomenon indicates that the alien mountain yellow cattle is in a state of high altitude acclimatization.But the native mountain yaks are well adapte to the high altitude and hypoxia environment.

Does high altitude increase risks of the elderly patients with coronary artery disease? / 老年心脏病学杂志（英文版）

Objective To assess the effect of altitude hypoxia on the elderly patients with coronary artery disease (CAD). Methods Three subject groups were surveyed during their train trip on the highest railroad--the Qinghai-Tibet Railway: 22 elderly individuals with documented CAD, 20 healthy elderly controls, and 20 healthy young controls, all of whom from Beijing near the sea level (76 m). Survey questions addressed clinical features of their healthy conditions and aspects of their coronary disease. The baseline study was performed at Xining at an altitude of 2261 m, and then during acute exposure to altitudes of 2808 m, 4768m, 5072 m and 4257 m by train for 24 hours. Resting pulse rate, blood pressure, oxygen saturation, electrocardiograph (ECG), and cardiac work estimated by the heart rate-blood pressure double product were obtained five times in each subject at different altitudes. Results On arrival to altitudes between 4768 m and 5072 m, the older passengers, especially those with preexisting coronary disease, had higher HR, higher BP, and lower SaO2, as well as more frequent abnormalities on ECG, as compared to the younger healthy subjects. As compared with the healthy elderly controls, incomplete right bundle branch block, left ventricular hypertrophy, and ST segment depression were more frequently seen in the elderly coronary patients (P<0.01). Cardiac work in group 1 was increased by 13% 12 hours after arrival to altitudes between 2808 m and 5072 m. Oxygen saturation decreased significantly with the altitude increasing by train ascent but improved after inhalation of oxygen. Most of the older subjects tolerated their sojourn at high altitude well except one who developed angina repeatedly with a significant ST segment depression. Conclusions Coronary events and ECG signs of myocardial ischemia are rare in elderly individuals with CAD who travel from sea level to moderate altitudes of 1500m to 2800 m. Patients with CAD who are well compensated at sea level generally tolerate this moderate altitude well. However, it would be prudent for patients with CAD going to altitude above 3000 m. The patients should consult their physician before undertaking a trip to such altitude.

Role of prostaglandins, nitric oxide and potassium channel in the blunting of hypoxic pulmonary vasoconstriction in the high altitude adaptive animal / 中国病理生理杂志

AIM: To investigate the possible role of prostaglandin, NO and potassium channel in the adaptive blunting of hypoxic pulmonary vasoconstriction (HPV) in the high altitude animal (pika). METHODS: The effect of L-NAME, indomethacin and 4-AP on the response of isolated lung strips of pika and Wistar rats instead of pulmonary artery to acute hypoxia were studied. RESULTS: (1) After inhibition of prostaglandins by indomethacin, the percentage increase in hypoxic constriction in lung tissue strip of pikas was greater than that in Wistar rats[(64.7?50.9)% vs (19.7?14.1)%], P