Neurodegenerative disease is characterized by progressive loss of neurons in specific brain regions that results in neuronal dysfunction of the central nervous system. Although the pathological mechanism is not fully established, the activation of glial cells mediated neuroinflammation appears to be involved. Heat shock protein 70 (HSP70) is originally described as intracellular chaperone, which plays an important role in protein quality control in cells. However, recent study showed that up-regulation of HSP70 had anti-inflammatory effects in the brain. HSP70 protected neurons from damage and improved neurological function by decreasing inflammatory response as indicated by inactivation of glial cells and inhibition of pro-inflammatory cytokine release. So it is of great significance to find new compounds targeting at HSP70 as neuroprotective agents to delay the progress of neurodegenerative disease. This review will focus on the role of HSP70 in neuroinflammation and the recent advances in using HSP70 as a target for the treatment of neurodegenerative disease.
Brain ; physiopathology ; Cytokines ; HSP70 Heat-Shock Proteins ; physiology ; Humans ; Inflammation ; pathology ; Neurodegenerative Diseases ; physiopathology ; Neurons ; pathology ; Neuroprotection ; Up-Regulation

Antigens, CD20 ; metabolism ; Female ; Follow-Up Studies ; Humans ; Interferon Regulatory Factors ; metabolism ; Leg ; pathology ; Lymphoma, Large B-Cell, Diffuse ; complications ; metabolism ; pathology ; surgery ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Skin Neoplasms ; complications ; metabolism ; pathology ; surgery ; Thrombocytopenia ; complications

Objective To investigate the effect of propofol on nNOS expression after focal cerebral ischemia-reperfusion in rats and the possible mechanism of protective effect of propofol on brain. Method Seventy-eight male Wistar rats, weighting 250 ~ 300 g, were randomly divided into 3 groups:(1)Sham operation group (S group, n=6) was performed with scham operation; (2) Ischemia-reperfusion group (group I-R, n=36) was subjected to 2-hour right middle cerebral artery occlusion and then reperfusion was followed, saline (1 mg/kg) was injected into the right lateral cerebral ventricle using microsyringe before reperfusion;(3) Propefol group (group P, n=36) was injected with propofol (1mg/kg) into the right lateral cerebral ventricle using microsyringe right after ischemia. Group I-R and group P were divided into 3 subgroups according to the reperfusion time: 1 h, 3 h and 6 h. The neurological function of all rats were tested before reperfusion. The cerebral infarction area of the whole brain was calculated with TIC staining (n=6). The pathological change of brain was observed from HE staining (n=6) and the nNOS protein expression was obtained by immuno- histochemical method (n=6). Results Compared with I-R group, the neurological function was better in group P(P

Background:Q fever endocarditis,a chronic illness caused by Coxiella burnetii,can be fatal if misdiagnosed or left untreated.Despite a relatively high positive rate of Q fever serology in healthy individuals in the mainland of China,very few cases of Q fever endocarditis have been reported.This study summarized cases of Q fever endocarditis among blood culture negative endocarditis (BCNE) patients and discussed factors attributing to the low diagnostic rate.Methods:We identified confirmed cases of Q fever endocarditis among 637 consecutive patients with infective endocarditis (IE) in the Peking Union Medical College Hospital between 2006 and 2016.The clinical findings for each confirmed case were recorded.BCNE patients were also examined and each BCNE patient's Q fever risk factors were identified.The risk factors and presence of Q fever serologic testing between BCNE patients suspected and unsuspected of Q fever were compared using the Chi-squared or Chi-squared with Yates' correction for continuity.Results:Among the IE patients examined,there were 147 BCNE patients,of whom only 11 patients (7.5％) were suspected of Q fever and undergone serological testing for C.burnetii.Six out of 11 suspected cases were diagnosed as Q fever endocarditis.For the remaining136 BCNE patients,none of them was suspected of Q fever nor underwent relevant testing.Risk factors for Q fever endocarditis were comparable between suspected and unsuspected patients,with the most common risk factors being valvulopathy in both groups.However,significantly more patients had consulted the Infectious Diseases Division and undergone comprehensive diagnostic tests in the suspected group than the unsuspected group (100％ vs.63％,P =0.03).Conclusions:Q fever endocarditis is a serious yet treatable condition.Lacking awareness of the disease may prevent BCNE patients from being identified,despite having Q fever risk factors.Increasing awareness and guideline adherence are crucial in avoiding misdiagnosing and missed diagnosing of the disease.

To study the chemical constituents of the aerial parts of Pulsatilla chinensis (Bge.) Regel, various chromatography methods were used. Seven triterpene glycosides were isolated from the n-BuOH extract. Their structures were identified as bayogenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4 ) -beta-D-glucopyranosyl (1 --> 6) -beta-D-glucopyranosyl ester (1), 3-O-alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4) -beta-D-glucopyranosyl (1 --> 6) -beta-D-glucopyranosyl ester (2), 3-O-alpha-L-rhamnopyranosyl (1 -->-2 ) -alpha-L-arabinopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl (1 --> 4 ) -beta-D-glucopyranosyl (1 --> 6 ) -beta-D-glucopyranosyl ester (3), 3-O-alpha-L-rhamnopyranosyl (1 --> 2 ) -[beta-D-glucopyranosyl (1 --> 4)] -alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4) -beta-D-glucopyranosyl (1 --> 6) -beta-D-glucopyranosyl ester (4), 3-O-alpha-L-rhamnopyranosyl (1 --> 2) -alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4) -beta-D-glucopyranosyl (1 --> 6 ) -beta-D-glucopyranosyl ester (5), hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4) -beta-D-glucopyranosyl (1 --> 6) -beta-D-glucopyranosyl ester (6) and pulsatilla saponin (7). Among them, compound 1 is a new compound. Compounds 2 -6 were isolated from this plant for the first time.
Glycosides ; chemistry ; isolation & purification ; Molecular Conformation ; Molecular Structure ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry ; Pulsatilla ; chemistry ; Saponins ; chemistry ; isolation & purification ; Triterpenes ; chemistry ; isolation & purification

Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg · kg(-1) · d(-1) glycyrrhizin and 40 mg · kg(-1) · d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-α (P < 0.01) and IL-1β (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.
Animals ; Antiviral Agents ; pharmacology ; Disease Models, Animal ; Drug Synergism ; Drug Therapy, Combination ; Glycyrrhizic Acid ; pharmacology ; Inflammation ; immunology ; Influenza A Virus, H1N1 Subtype ; drug effects ; Interleukin-1beta ; immunology ; Interleukin-6 ; immunology ; Lung ; immunology ; virology ; Mice ; Orthomyxoviridae Infections ; drug therapy ; Pneumonia, Viral ; drug therapy ; Ribavirin ; pharmacology ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVETo assess the operative methods of delayed acetabular fractures and the operative results.

METHODSThe operative approaches, procedures, results and complications of the delayed acetabular fractures between August 1993 and August 2001 in Jishuitan Hospital were evaluated retrospectively.

RESULTSThirty-two patients were followed up 49.6 months on average. Sciatic nerve palsy was found in 1 patient. Excellent functional results of hip joints were found in 3 patients, good in 16, fair in 10, and poor in 3. Ectopic bone formation was observed in 6 patients and necrosis of the femoral head in 3.

CONCLUSIONCareful selection of operative indications of delayed acetabular fractures in combination with proper operative approach and appropriate reduction and fixation, good results can be obtained.

Acetabulum ; injuries ; surgery ; Adult ; Female ; Follow-Up Studies ; Fracture Fixation, Internal ; methods ; Fractures, Bone ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Treatment Outcome

Objective To investigate the changes of hydrogen sulfide (H_2S) level in plasma in order to explore the role of H_2S in the development of pulmonary hypertension (PH) secondary to congenital heart disease (CHD).Methods There were 9 CHD patients and 9 normal children in this study. The plasma concentration of H_2S and pulmonary artery pressure (PAP) of each child were measured. Meanwhile, the relationship between H_2S level and PAP was analyzed.Results The plasma level of H_2S in the group of CHD significantly decreased compared with control group (32.13?2.25) ?mol/L vs [(43.69?2.05)?mol/L, P

OBJECTIVETo explore therapeutic effects of bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle,and analyze manipulative reduction mechanism.

METHODSFrom 2005 to 2008, 95 patients with over degree II supination-eversion fractures of ankle were treated respectively by manipulation and operation. There were 43 cases [11 males and 32 females with an average age of (44.95 +/- 12.65) years] in manipulation group, and 2 cases were degree II, 11 cases were degree III, and 30 cases were degree IV. There were 52 cases [21 males and 31 females with an average age of (39.96 +/- 13.28) years] in operative group,and 6 cases were degree II, 18 cases were degree III, and 28 cases were degree IV. Bone setting manipulation and hard splint external fixation were applied to manipulative group. Operative reduction internal fixation was performed in operative group. X-ray was used to evaluate reduction of fracture before and after treatment, 2 months after treatment. Ankle joint function was evaluated according to Olerud-Molander scoring system after 6 months treatment.

RESULTSAll patients were followed up with good reduction. Three cases occurred wound complication in operative group, but not in manipulative group. In manipulation group, 19 cases got excellent results, 20 cases good and 4 cases fair; while in operative group, 30 cases got excellent results, 20 cases good and 2 cases poor. There were no significant differences in fracture reduction and ankle joint function recovery between two groups (P > 0.05). Efficacy of operative treatment was better than that of manipulative treatment at degree IV fracture (P < 0.05).

CONCLUSIONBone setting manipulation is a good method for treating supination-eversion ankle joint fractures, which has advantages of simple and safe operation, reliable efficacy. For ankle join fracture at degree IV, manipulative reduction should be adopted earlier, and operative treatment also necessary

Adult ; Ankle Injuries ; physiopathology ; therapy ; Ankle Joint ; physiology ; Case-Control Studies ; Female ; Fractures, Bone ; physiopathology ; therapy ; Humans ; Male ; Manipulation, Orthopedic ; methods ; Supination

In order to minimize the residual tert-butyl alcohol (TBA) level in cyclodextrin complex prepared by freeze drying TBA/water cosolvent system, the formulation and lyophilization procedure that may influence the residual TBA was studied. Residual TBA in freeze dried cyclodextrin complex was determined by gas chromatography. The significant formulation and processing factors that influence residual TBA were identified by adjusting the initial TBA concentration in cosolvent, selecting cyclodextrin type (beta-cyclodextrin or hydroxypropyl beta-cyclodextrin), changing sample volume in flasket, altering freezing mode (fast freezing or slow freezing) and modifying the duration of secondary drying. The results show that the amorphous cyclodextrin material (hydroxypropyl beta-cyclodextrin), initial low TBA concentration in cosolvent and fast freezing would lead to high TBA residue in cyclodextrin complex, annealing was effective in reducing the residual TBA. The duration of secondary drying had no distinct effect on residual TBA. It is concluded that in order to reduce residual TBA in cyclodextrin complex prepared by lyophilization monophase solution, the initial TBA concentration in cosolvent should be higher than the crystal formation concentration, the appropriate cyclodextrin type and freeze drying processing should be choosen.
2-Hydroxypropyl-beta-cyclodextrin ; Anti-Inflammatory Agents ; chemistry ; Budesonide ; chemistry ; Chromatography, Gas ; Drug Residues ; analysis ; chemistry ; Freeze Drying ; methods ; Solvents ; chemistry ; Water ; chemistry ; beta-Cyclodextrins ; chemistry ; tert-Butyl Alcohol ; analysis ; chemistry