OBJECTlVE To study the reIationship between microRNA(miRNA)-122 and Iiver injury in-duced by anti-tubercuIosis drugs,and to discover the new biomarkers for earIy diagnosis of this type of Iiver injury. METHODS mice were given 2 mL isoniazid oraIIy at 90 mg·kg-1 . BIood and Iiver tissue sampIes were coIIected at 1,3,5,7,14,21 and 28 d after administration of isoniazid. Serum gIutamic-pyruvic transaminase( GPT)and gIutamic-oxaIoacetic transaminase( GOT)IeveIs were determined using an automatic biochemicaI anaIyzer. Cu/ Zn-superoxide dismutase( Cu/ Zn-SOD ) activity and maIondiaIdehyde( mDA)content were detected by biochemicaI method. ReaI-time qPCR was used to measure the expression of miRNA-122. RESULTS GPT and GOT IeveIs were significantIy higher at 14 and 21 d(P﹤0.05)than in the controI. Cu/ Zn-SOD began to decIine whiIe mDA began to increase after 5 d(P﹤0.05). miRNA-122,which progressiveIy decreased after administration,was reduced to the mini-mum 0.58 ±0.02 at 14 d. There were good correIations between miRNA-122 and GPT,Cu/ Zn-SOD, mDA(the correIation coefficients were -0.370,0.268,and -0.298,respectiveIy),but no correIation with GOT was observed. CONCLUSlON The tissue miRNA-122 profiIe can be used as a sensitive marker for anti-tubercuIosis drug-induced Iiver injury,which couId contribute to the earIy diagnosis of Iiver injury.

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.

Objective To study the association between impaired fasting glucose (IFG) and cognitive impairment in community elderly residents.Methods A total of ≥60 years old 1223 people were divided into normal fasting glucose (NFG) group (n=981) and IFG group (n=242).Their baseline data were recorded,their cognitive function was assessed according to the MMSE score.Results The education level,BMI,serum FBG,TG,LDL-C levels,incidence of hypertension and hyperlipidemia were significantly higher while the serum HDL-C level was significantly lower in IFG group than in NFG group (P＜0.05,P＜0.01).The incidence of cognitive impairment was significantly higher while the score of MMSE,orientation,attention and calculation,immediate recall and language was significantly lower in IFG group than in NFG group (40.50％ vs 21.51％,24.76±5.38 vs 26.60±4.26,9.07±1.81 vs 9.48±1.15,3.39±2.00 vs 3.88±1.81,2.93±0.41 vs 2.98±0.24,6.74±1.51 vs 7.18±1.15,P＜0.01).Age,female sex,LDL-C and IFG were risk factors for cognitive impairment in the elderly (P＜0.01,P＜0.05) while the education level was a protective factor for cognitive impairment in the elderly (P=0.000).Conclusion IFG is an independent risk factor for cognitive impairment in the elderly.Early diagnosis and intervention can improve cognitive function in the elderly.

Hypertension is one of the most important diseases that threaten human health, and has become a global problem. In recent years, the prevalence of hypertension in children has increased significantly year by year, and hypertension in children has a trajectory phenomenon, which is easy to cause cognitive damage and other target organ damage. Therefore, it is necessary to be alert and attached to the relationship between hypertension and cognitive impairment in children. This article reviews the epidemiological characteristics, etiology, diagnostic criteria of hypertension and pathophysiological mechanisms of cognitive impairment caused by hypertension in children.

Post-stroke cognitive impairment (PSCI) is one of the common complications of stroke,which has a significant impact on the life of patients.Studies have shown that the incidence of PSCI varies from region to region,and is correlated with demographic and vascular risk factors,or is significantly different due to stroke types and characteristics.The specific mechanism of PSCI remains unclear,but early identification of its risk factors is helpful for early intervention.This article reviews the risk factors of PSCI.

Objective To observe the effect of transcranial direct current stimulation (tDCS) with mirror neuronal rehabilitation training system (MNST-V1.0) in post-traumatic unconscious patients after severe craniocerebral injury. Methods A prospective, self controlled and open-label method was used. Thirty-six post-traumatic unconscious patients with severe craniocerebral injury from January 2016 to July 2017 were selected. Four cases of the patients did not complete the treatment and the last 32 cases completed the study. All patients were given routine wake-up therapy, and tDCS combined with MNST-V1.0 (20 min/time, 1 time/d, 6 times/week, a total of 8 weeks) was given at the same time. The Glasgow coma scale (GCS), JFK coma recovery scale and Four coma rating scale before treatment and 2, 4, 8 weeks after treatment were recorded. Results The scores of open reaction, language and motor response score of GCS 2, 4, 8 weeks after treatment were significantly higher than those before treatment:(1.56 ± 0.82), (2.06 ± 1.01) and (3.11 ± 1.45) scores vs. (1.00 ± 0.45) scores, (2.23 ± 1.06), (2.56 ± 1.08) and (3.02 ± 1.04) scores vs. (1.00 ± 0.61) scores, (2.79 ± 1.12), (3.22 ± 1.33) and (4.44 ± 1.07) scores vs. (1.00 ± 0.54) scores, and there were statistical differences (P ＜ 0.01 or ＜0.05). The scores of hearing, vision, movement, speech response, communication and arousal of JFK coma recovery scale 2, 4, 8 weeks after treatment were significantly higher than those before treatment, and there were statistical differences (P＜0.01). The scores of open reaction, sport reaction, brainstem response of Four coma rating scale 2, 4, 8 weeks after treatment were significantly higher than those before treatment, and there were statistical differences (P＜0.05); there was no statistical difference in respiratory score of Four coma rating scale before and after treatment (P＞0.05). Conclusions The tDCS combined with MNST-V1.0 can improve the consciousness level in post-traumatic unconscious patients with severe craniocerebral injury, and have the effect of promoting awakening.

Objective:To investigate the safety of intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel in patients with unruptured intracranial aneurysms accepted stent-assisted coil embolization, and explore the effect of tirofiban on perioperative thrombotic events.Methods:The clinical data of 275 patients with unruptured intracranial aneurysms who underwent stent assisted coil embolization in our hospital from January 2016 to December 2019 were retrospectively collected. Among them, 110 patients admitted to our hospital from January 2016 to December 2017 only received preoperative oral administration of aspirin and clopidogrel combined with antiplatelet treatment (classic group), and 165 patients admitted to out hospital from January 2018 to December 2019 received intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel (improved group). The differences of perioperative safety and thrombotic events between the two groups were compared and analyzed.Results:The incidence of intraoperative visual thrombotic events in the classic group and the improved group were 6.4% (7/110) and 1.2% (2/165), respectively, with significant difference ( P<0.05); the incidence of postoperative thrombotic events was 4.5% (5/110) and 2.4% (4/165), respectively, without significant difference ( P>0.05); the incidence of urethrorrhagia was 9.1% (10/110) and 21.2% (35/165), respectively, with significant difference ( P<0.05); and the incidence of gingival hemorrhage was 13.6% (15/110) and 19.4% (32/165), respectively, without significant difference ( P>0.05). No acute gastrointestinal hemorrhage or cerebral hemorrhage occurred in both groups; urethrorrhagia and gingival hemorrhage were transient and relieved spontaneously. Conclusion:Intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel can reduce the incidence of intraoperative visual thrombotic events without increasing the risk of hemorrhage in stent-assisted coil embolization of unruptured intracranial aneurysms.

【Objective】 To investigate the effects of high-dose hyperbaric trioxygen autologous blood therapy (HOT) on oxygenation index (PaO2/FiO2) and serum inflammatory factors in dogs with acute respiratory distress syndrome (ARDS). 【Methods】 Twelve healthy adult beagles were randomly divided into 3 groups (n=4). The blank group was injected with normal saline intravenously. The ARDS model was established by intravenous injection of oleic acid (0.12 mL/kg) in the ARDS group and ARDS+ HOT group. The mark of a successful model is that the oxygen and index (PaO2/FiO2) <300 mmHg. In the ARDS+ HOT group, after the ARDS model was established, 16 G indwelling needle was used to puncture the left femoral vein and connect the line of the HOT device. Venous blood (50 mL/ dog) was collected from the femoral vein under negative pressure to the blood storage bottle (100 mL blood storage bottle), and then the blood collection was stopped and the gas injection switch of the HOT device was turned on. Inject 50 mL of 20ng/dL trioxygen gas into the blood storage bottle. After gas injection, turn the blood storage bottle upside down three times to fully trioxidize the blood and then inject it back into the dog. Repeat this treatment for 10 cycles. PaO2 and PaO2/FiO2 were detected before treatment and at 1, 2, 3, 4, 5 h after treatment. The serum was retained after treatment, and the expressions of inflammatory cytokines (IL-6, IL-8) and myeloperoxidase (MPO) were detected by ELISA. The animals were euthanized, and the gross lung morphology of the dogs was observed at autopsy. The dorsal segment of the left lower lobe of the lung was taken for pathological section HE staining, and the morphological changes of the lung tissue were observed under the microscope. 【Results】 After 5 hours of treatment, the PaO2/FiO2 of blank group was 481.85±35.31, and that of ARDS group was 183.67±20.18, which was significantly lower than that of blank group (P<0.01). The ARDS HOT group was 271.90±21.35, which was significantly higher than the ARDS group (P<0.01). The inflammatory factor IL-6 was (206.49±38.85) pg/mL in the blank group, and (293.12±30.38) pg/mL in the ARDS group, which was significantly higher than that in the blank group (P<0.01). There was a significant difference between the ARDS HOT group and ARDS group (221.56±46.69) pg/mL (P<0.01). The results of inflammatory factor IL-8 detection showed that the IL-8 in ARDS group was increased compared with the blank group (P<0.01); and the IL-8 in ARDS HOT group was decreased compared with ARDS group (P<0.01). Myeloperoxidase MPO test results showed that the blank group was (505.58±73.94) pg/mL, and the ARDS group was (605.69±108.88) pg/mL, which was significantly higher than the blank group (P<0.05). The ARDS HOT group was (476.52±103.85) pg/mL, which was significantly lower than the ARDS group (P<0.05). Microscopic examination of lung pathology showed that the lung tissue injury in ARDS HOT group was significantly reduced compared with ARDS group. 【Conclusion】 HOT can reduce the inflammation and injury of lung in ARDS model dogs through significantly increasing the PaO2/FiO2, down-regulating the expression of MPO, then inhibiting the activity of neutrophils and reducing the levels of IL-6 and IL-8.

Histone lysine specific demethylase 1 (LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound (IC = 3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound (IC = 49 nmol/L, and = 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3K4me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency of compound . Compound also showed strong antiproliferative activity against four leukemia cell lines (OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, significantly inhibited colony formation and caused remarkable morphological changes. Compound induced expression of CD86 and CD11b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation. The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazole-fused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1A inhibitors.

In order to overcome the challenges of insufficient restriction enzyme sites, and construct a fusion-expression vector with flexible fusion direction, we designed an LB cloning system based on the type IIS and type IIT restriction enzymes LguⅠ and BbvCⅠ. The LB cloning system is constructed by inserting the LB fragment (GCTCTTCCTCAGC) into the multiple cloning site region of the broad-host plasmid pBBR1MCS-3 using PCR. The LB fragment contains partially overlapped recognition sites of LguⅠ and BbvCⅠ. Therefore, the same non-palindromic sequence will be generated by these two restriction endonucleases digestion. This feature can be used to quickly and flexibly insert multiple genes into the expression vector in a stepwise and directed way. In order to verify the efficacy of the cloning system, two glycosyltransferase genes welB and welK of Sphingomonas sp. WG were consecutively fused to the LB cloning vector, and the recombinant plasmid was transferred into Sphingomonas sp. WG by triparental mating. The results showed that gene fusion expression has little effect on sphingan titer, but enhanced the viscosity of sphingan. The viscosity of the sphingan produced by recombinant strain Sphingomonas sp. WG/pBBR1MCS-3-LB-welKB was 24.7% higher than that of the wild strain after fermentation for 84 h, which would be beneficial for its application. In conclusion, the application of LB cloning system were verified using Sphingomonas sp. WG. The LB cloning system may provide an efficient tool for fusion expression of target genes.
Base Sequence ; Cloning, Molecular ; Fermentation ; Plasmids/genetics* ; Sphingomonas/metabolism*