Objective To evaluate the role of mammalian target of rapamycin (mTOR) signaling pathway in dexmedetomidine-induced reduction of renal ischemia-reperfusion (I/R) injury in rats and the relationship with hypoxia-inducible factor 1 (HIF-1α).Methods Seventy-two male Sprague-Dawley rats, aged 10-12 weeks, weighing 220-260 g, were randomly divided into 4 groups (n=18 each) using a random number table: sham operation group (group S), group I/R, dexmedetomidine group (group Dex) ,and rapamicyn + dexmedetomidine group (group Rpm+Dex).Renal I/R was produced by occlusion of bilateral renal pedicles for 35 min follow by reperfusion in anesthetized rats in I/R, Dex and Rpm+Dex groups.Bilateral renal pedicles were only exposed, and then the abdominal cavity was closed in group S.Dexdetomidine 50 μg/kg was injected intraperitoneally at 30 min before I/R in group Dex.In group Rpm+Dex, rapamicyn 1.5 mg/kg and dexdetomidine 50 μg/kg were injected intraperitoneally, and renal I/R model was established 30 min later.Immediately after onset of reperfusion, and at 4 and 24 h of reperfusion (T1-3) , blood samples were collected from the caudal vein for measurement of serum creatinine and blood urea nitrogen (BUN) concentrations.After blood sampling at T1-3, the rats were sacrificed, and the renal specimens were obtained for detection of HIF-1αt, erythropoietin (EPO) and mTOR expression by Western blot.Their kidneys were removed at T3, and cut into sections which were stained with haematoxylin and eosin and examined under microscope.Acute renal tubular necrosis was scored.The cell apoptosis in renal tissues was detected by TUNEL assay, and apoptosis index (AI) was calculated.Results Compared with group S,the concentrations of serum creatinine and BUN, expression of HIF-1α, EPO and mTOR at T2,3 , AI at T3 and acute renal tubular necrosis score were significantly increased in the other three groups (P＜ 0.05).Compared with group I/R, the concentrations of serum creatinine and BUN were significantly decreased, and the expression of HIF-1α, EPO and mTOR was up-regulated at T2,3 , and AI and acute renal tubular necrosis score were decreased in group Dex (P＜0.05) , and no significant change was found in the parameters mentioned above in group Rpm + Dex (P ＞ 0.05).Conclusion The mTOR signaling pathway is involved in dexmedetomidine-induced reduction of renal I/R injury, which may be related to dexmedetomidine-produced up-regulation of HIF-1α expression in renal tissues of rats.

Objective To investigate the protection effect of dexmedetomidine against H2O2 injury in Human renal tubular epithelial cells(HK-2 cells). Methods HK-2 cells cultured in vitro were randomly divided into four groups(n = 24): control group, dexmedetomidine pretreatment group, H2O2 injury group, H2O2 injury +dexmedetomidine pretreatment group. Cell viabilities were measured by MTS assay, cell apoptosis were detected using flow cytometry, and expression of HIF-1α protein was quantified by western blot. HK-2 cells were divided into 8 groups by combining with three treatment factors such as PI3K inhibitor LY294002, dexmedetomidine and H2O2 injury. MTS assay was used to detect cell viability and western blot was used to quantify protein expression of HIF-1α,Bcl-2 and Bax after treatment in each group. Results Dexmedetomidine significantly increased the level of HIF-1α、 Bcl-2 in HK-2 cells after H2O2 injury, thus improved viabilities and reduced apotosis of cells. Moreover, effect on H2O2 injury cells of Dexmedetomidine was reversed by PI3K inhibitor LY294002. Conclusion Dexmedetomidine could protect against H2O2 injury by up-regulating HIF-1α expression through activating PI3K/Akt/mTOR signaling pathway in HK-2 cells.

Objective To explore the value of the diagnosis of middle cerebral artery (MCA) stenosis with transcranial Doppler ultrasound (TCD). Methods The clinical data in patients with ischemic cerebrovascular disease examined with digital subtract angiography (DSA)and TCD were analyzed retrospectively. DSA was used as a gold standard to analyze the sensitivity and specificity of the diagnosis of MCA stenosis with TCD. The normal and TCD blood flow velocity with different degrees of stenosis were compared. The best cut-off point of the TCD blood flow velocity of MCA at different degree of stenosis was calculated. Results DSA confirmed that 103 patients had MCA stenosis or occlusion, in which 12 were mild stenosis, 22 were moderate stenosis, 40 were severe stenosis, and 39 were occlusion. Compared to DSA, the sensitivity of TCD in detection of moderate and severe MCA stenosis or occlusion was 78. 8%, the specificity was 96. 0%, and the accuracy was 93. 0%, the missed diagnosis rate was 21. 2%, and the misdiagnosis rate was 4. 0%. As to the blood flow velocity, there was no significant difference between the mild stenosis and normal groups; while there was significant difference between the moderate stenosis and normal groups (P ＜0. 001). In addition, there was no significant difference in blood flow velocity between the moderate stenosis and severe stenosis groups. Determining the cut-off value of the best peak systolic velocity of the moderate stenosis was 163. 5 cm/s, while the best cut-off value of the mean velocity was 108. 5 cm/s. Conclusions TCD has certain advantages in the diagnosis of the MCA stenosis or occlusion, and it can be used as a safe and inexpensive screening means before DSA examination.

Objective:To observe the effect of acupuncture in the treatment of accommodative myopia in children.Methods:A total of 76 children with accommodative myopia who met the inclusion criteria were divided into a control group or a test group according to the random number table method,with 38 cases in each group.The control group was given education on eye hygiene,and the test group was treated with acupuncture twice a week for 2 months in addition to the intervention used in the control group.The patient's uncorrected visual acuity(UCVA),refraction,and axial length(AL)were measured before treatment and 1 month and 2 months after treatment.Results:After 1 month of treatment,there was no significant difference in the UCVA between the two groups(P＞0.05);after 2 months of treatment,the UCVA of the test group was better than that of the control group(P＜0.05).After 1 and 2 months of treatment,the refraction of the two groups was significantly different from that before treatment(P＜0.01),but there was no significant difference between the two groups(P＞0.05).After 1 and 2 months of treatment,the AL in the control group was increased compared with that before treatment(P＜0.05),while there was no significant change in the test group(P＞0.05),and there was no significant difference between the two groups(P＞0.05).Conclusion:Acupuncture treatment can improve UCVA in children with accommodative myopia.

Objective To observe the effects of repeated Botulinum toxin type A (BTX-A) injection on lower limb spasticity after stroke.Methods 180 cases with lower limb spasticity after stroke were divided into the treatment group (n=90) and the control group (n=90). The treatment group was treated with BTX-A injection twice in the spastic muscles at interval of 3~6 months, while both the treatment group and the control group accepted the rehabilitation based on the neurodevelopmental therapy. They were assessed with modified Ashworth Scale (MAS), Fugl-Meyer Lower Limb Assessment (FMAL), Berg Balance Scale (BBS), modified Barthel Index (MBI) before each injection, and 3 d, 7 d, 1 month, 3 months after each injection or the same time for the controls. Results There was significant difference in scores of MAS, FMAL, BBS, MBI for the treatment group among before and 3 d, 7 d, 1 month after each injection (P<0.05), but not significant between 2 injections (P<0.05). There was significant difference in scores of all the assessment between the treatment and control group at the same time (P<0.01). Conclusion Repeated intramuscular injection of BTX-A can reduce the spasticity of lower limb after stroke.

Dehydration is one of the key steps in the biosynthesis of mycolic acids and is vital to the growth of Mycobacterium tuberculosis (Mtb). Consequently, stalling dehydration cures tuberculosis (TB). Clinically used anti-TB drugs like thiacetazone (TAC) and isoxyl (ISO) as well as flavonoids inhibit the enzyme activity of the β-hydroxyacyl-ACP dehydratase HadAB complex. How this inhibition is exerted, has remained an enigma for years. Here, we describe the first crystal structures of the MtbHadAB complex bound with flavonoid inhibitor butein, 2',4,4'-trihydroxychalcone or fisetin. Despite sharing no sequence identity from Blast, HadA and HadB adopt a very similar hotdog fold. HadA forms a tight dimer with HadB in which the proteins are sitting side-by-side, but are oriented anti-parallel. While HadB contributes the catalytically critical His-Asp dyad, HadA binds the fatty acid substrate in a long channel. The atypical double hotdog fold with a single active site formed by MtbHadAB gives rise to a long, narrow cavity that vertically traverses the fatty acid binding channel. At the base of this cavity lies Cys61, which upon mutation to Ser confers drug-resistance in TB patients. We show that inhibitors bind in this cavity and protrude into the substrate binding channel. Thus, inhibitors of MtbHadAB exert their effect by occluding substrate from the active site. The unveiling of this mechanism of inhibition paves the way for accelerating development of next generation of anti-TB drugs.
Amino Acid Sequence ; Bacterial Proteins ; chemistry ; metabolism ; Catalytic Domain ; Enzyme Inhibitors ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Hydro-Lyases ; antagonists & inhibitors ; chemistry ; Molecular Sequence Data ; Mycobacterium tuberculosis ; drug effects ; enzymology ; Protein Binding ; drug effects ; Protein Multimerization ; drug effects ; Protein Structure, Secondary ; Sequence Alignment

Objective:To observe and analyze the intervention effect of logotherapy on anxiety and depression in patients with chronic glomerulonephritis (CGN).Methods:Selected 102 CGN patients from March 2019 to May 2020 in Beijing Tiantan Hospital Affiliated to Capital Medical University as the research objects, the general information of the patients was collected, and the patients were randomly divided into the observation group and the control group with 51 cases in each group. The control group was given routine nursing intervention for CGN patients, and the observation group was given logotherapy therapy intervention based on the intervention of the control group. The differences in the scores of the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) between the two groups before and after 3 months of intervention.Results:There were no significant differences in SAS and SDS scores before and after intervention in the control group ( P>0.05). The SAS and SDS scores in the observation group after 3 months of intervention were (40.67 ± 4.17), (48.74 ± 5.01) points, which were significantly lower than (51.34 ± 5.04), (55.19 ± 5.49) points in the control group ( t=8.37, 3.32, both P<0.01). Conclusions:The positive psychological intervention of patients with logotherapy can effectively improve the anxiety and depression of patients with CGN.