Objective To investigate the protective effect of dimethyl fumarate(DMF)on doxorubicin(DOX)-induced cardiac injury in mice and its possible mechanism.Methods Eighteen male C57BL/6J mice were selected and randomly divided into control group,model group and treatment group,with 6mice in each group.In the model group,DOX(2.5mg/kg)was injected intraperitoneally for two weeks,once every three days,with a total of 15mg/kg;the control group was given equal proportion of normal saline.The experi-mental group was also treated with DOX for two weeks,and was given DMF(25mg/kg)once a day for consecutive seven days after the first week.The cardiac function of mice was monitored at0,3,7 and 14 days.The atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)mRNA expression of myocardial were detected by real-time quantitative polymerase chain reaction(RT-qPCR),and plasma creatine kinase isoenzyme(CK-MB)and lactic acid dehydrogenase(LDH)levels were measured by ELISA(enzyme-linked immunosorbent assay).Hematoxylin-eosin(HE)staining was used to observe myocardial structure.Malondialdehyde(MDA),reduced glutathione(GSH),and oxidized glutathione(GSSG)content and superoxide dismutase(SOD)activity were measured;Western blot was used to detect the expression of nuclear factor erythroid-2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and glutathione peroxidase 4(GPX4),a key protein of ferroptosis.Results In the model group,the heart function of mice continued to decline and reached the lowest level at 14days,left ventricular ejection fraction(LVEF)and left ventricular short-axis shortening rate(LVFS)were significantly lower than those in control group.Body weight and heart weight-to-tibia length ratio were lower than those of control group,while the mRNA expression of cardiac ANP and BNP was increased,the plasma CK-MB and LDH were increased,accompanied by cardiomyocyte edema,muscle fiber rupture and inflammatory infiltration.However,the cardiac dysfunction of mice in the treatment group was improved,and the myocardial damage and structural destruction were less severe.In addition,MDA and GSSG contents in the model group were significantly higher than those in the control group,GSH level and SOD activity were lower than those in the control group,and the expressions of Nrf2,HO-1 and GPx4 were decreased.Compared with the model group,the cardiac oxidative stress in the treatment group was improved,and the expressions of Nrf2,HO-1 and GPx4 were also up-regulated.Conclusion DMF inhibits fer-roptosis and alleviates DOX-induced cardiac oxidative stress through upregulation of Nrf2/HO-1/GPX4 pathway,thus improving cardi-ac damage.

Objective To evaluate the mechanism of governor vessel electroacupuncture in rats with post-stroke limb spasm by observing the changes of glutathione antioxidant system-related factors.Methods A total of 60 SD rats were randomly divided into the normal group(n=12),sham operation group(n=12)and modeling group(n=36).The middle cerebral artery obstruction model was prepared by thread approach method in the modeling group,and 24 rats with successful modeling were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.At the 3rd day after modeling,the electroacupuncture group was treated with electroacupuncture at three acupoints of the governor vessel,namely,"Dazhui"(GV14),"Jizhong"(GV6)and"Houhui"(anteromedial of the transverse process of the sixth lumbar vertebra),for 30 min each time,once a day for 7 days.The neurological function of rats was assessed by Zea Longa neurological deficit score.The muscle tension of rats was detected by modified Ashworth dystonia rating and electrophysiological tracing method.The brain tissue water content was measured by the dry-wet weight method.The volume of cerebral infarction of rats was measured by the TTC staining method.The contents of glutathione(GSH),catalase(CAT),oxidized glutathione(GSSG),superoxide dismutase(SOD),and malondialdehyde(MDA)in the cortex of rats were detected by colorimetry.The protein and mRNA expressions of glutathione reductase(GR),glutamate cysteine ligase(GCL)C,GCLM,and glutathione peroxidase 4(GPX4)in the cortex of rats were measured by Western blotting and real-time PCR,respectively.Results Compared with rats in the normal and sham operation groups,the Zea Longa neurological deficit score,modified Ashworth dystonia rating,the volume of cerebral infarction,brain tissue water content,and GSSG and MDA contents in cortex were increased in the model group,the tension signal value and the proteins and mRNA expressions of GR,GCLC,GCLM,and GPX4 in cortex were decreased,and the contents of GSH,CAT,and SOD in cortex were decreased(P＜0.05).Compared with the model group,the Zea Longa neurological deficit score,modified Ashworth dystonia rating,the volume of cerebral infarction,brain tissue water content,and GSSG and MDA contents in cortex were decreased in the electroacupuncture group,the tension signal value and the proteins and mRNA expressions of GR,GCLC,GCLM,and GPX4 in cortex were increased,and the contents of GSH,CAT,and SOD in cortex were increased(P＜0.05).Conclusion Governor vessel electroacupuncture can improve the severity of post-stroke limb spasm in rats,and its mechanism may be related to the regulation of glutathione antioxidant system in cerebral cortex.

OBJECTIVE The abnormal amyloid-β(Aβ)and oxidative stress assiociated with the progression of Alzheimer disease(AD).Quercetin has been reported to possess antioxidant and anti-inflammatory properties in neurodegenerative disorders.In this present study,we designed to characterize the mechanisms by which quer-cetin exerts neuroprotective effects in murine neuroblas-toma N2a cells stably expressing human Swedish mutant amyloid precursor protein(N2a/APP).METHODS N2a/APP cells were treated with quercetin at concentrations of 10,20 and 50 μ mol·L-1 for 24 h.Cell viability was examined with CCK-8 assays.The protein levels of ERK1/2 and Akt were detected by Western blotting.Intra-cellular reactive oxygen species(ROS)was detected by a fluorescent probe 2,7-dichlorofluorescein diacetate(DCFH-DA).The mitochondrial membrane potential(Δψ m)in N2a/APP cells was detected by using JC-1 staining method.Immunofluorescence was used to detect the generation of 8-hydroxy-2′-deoxyguanosine(8-OHdG)and 4-hydroxynonenal(4-HNE).RESULTS Quercetin attenuated the enhancement of p-ERK1/2,reductions of p-Akt,and decreased levels of APP expression.More-over,quercetin alleviated loss of mitochondria membrane potential(MMP)since it attenuates these oxidative stress,as reflected in the levels of ROS,4-HNE and 8-OHdG,was elevated in N2a/APP cells and these effects were again ameliorated by quercetin.CONCLUSION Neuroprotection by quercetin in N2a/APP cells involves normalizing the impaired mitochondrial function and reducing oxidative stress via inactivation of the ERK1/2 and activation of the Akt pathways.

Objective:To investigate characteristics of the 18F-flurodeoxyglucose ( 18F-FDG) uptake intensity and ranges in distinct hepatic alveolar echinococcosis lesions. Methods:The clinical data of 39 patients with position emission tomography during Jan 2017 to Dec 2019 in the First Affiliated Hospital of Xinjiang Medical University were enrolled. Among them, there were 17 males and 22 females, aging from 15 to 65 years (median 34 years). Lesions were classified into six groups based on heterogenic scales of calcification and liquefaction: A. non-calcified and non-liquefied ( n=7); B. obvious calcified and non-liquefied ( n=7); C. partial calcified and partial liquefied( n=10); D. obvious calcified and partial liquefied ( n=5); E. partial calcified and subtotal liquefied ( n=5); F. obvious calcified and subtotal liquefied ( n=5). Tumor to background ratio (TBR) and width (W) of lesion infiltrative boundary were measured and calculated. Statistical comparison using Mann-Whitney U test as well as correlation analysis was performed. Results:TBR values [ M( Q1, Q3)] for each group were 4.40(3.66, 7.03), 2.55(1.69, 3.60), 3.73(3.37, 5.21), 2.90(2.75, 3.60), 3.80(3.49, 6.36), 2.49(2.21, 3.97), among which A>B, A>D, A>F, C>B, E>B ( U=3.0, 4.0, 4.5, 11.0, 5.0, all P<0.05); From the perspective of the calcification in each group, it was found that the lighter the calcification was, the greater the TBR value was. W values [ M( Q1, Q3)] for each group were [12.5(10.0, 19.5), 11.2(10.5, 12.5), 12.2(10.9, 13.2), 7.8(7.3, 9.3), 10.0(7.3, 13.4), 7.3(6.8, 7.6)] mm, among which A>D, A>F, B>D, B>F, C>D, C>F (all U=0, all P<0.05); According to the degree of calcification and liquefaction of lesions in each group, the lighter the calcification was, the greater the W value was; The heavier the liquefaction was, the smaller the W value was. A mild strength linear correlation has been observed between the TBR value and W value ( r=0.4136, P<0.05). Conclusions:Less calcification and liquefaction implicated higher 18F-FDG uptake intensity and wider range. Radical resection margins and tissue sampling should be individualized based on different lesion features in surgical treatment.

Objective:To construct a new reporter mycobacteriophage, ΦFN, based on a nanoluciferase (Nluc) reporter system, and to analyze its ability to detect drug resistance in Mycobacterium tuberculosis ( Mtb). Methods:A Nluc reporter system controlled by P furAma promoter was constructed and integrated into Mycobacterium smegmatis ( Msm) genome to assess its reporting ability in mycobacteria. Then the P furAma- nluc reporter system was integrated into TM4 mycobacteriophage genome to construct a new phage termed ΦFN. A rapid procedure for detecting drug resistance in mycobacteria using ΦFN was established by adjusting conditions such as drug exposure time and time of infection. The susceptibility of 52 clinical isolates of Mtb with known drug resistance to three first-line anti-tuberculosis drugs were tested in 96-well plates. Results:The recombinant Msm mc 2155 expressing P furAma- nluc repoerter system could generate luminescence signal at a low limit of 100 colony-forming unit (CFU), which was lower than the previously reported nluc system controlled by Pleft promoter. The detection limit of ΦFN for mycobacteria reached 100 CFU within 24 h by luminescent microplate reader. After 48 h of antibiotic exposure and 24 h of phage incubation, no luminescence signal could be detected when susceptible strains were below 10 5 CFU, which could effectively distinguish susceptible strains and rapidly detect drug resistance. The drug susceptibility of 52 clinical isolates of Mtb to rifampin, isoniazid and streptomycin was tested using ΦFN, and the accuracy was 51/52, 48/52 and 49/52, respectively, by using the conventional drug susceptibility test, Lwenstein-Jensen culture medium assay, as reference. Conclusions:The new recombinant luminescent reporter phage, ΦFN, showed high accuracy in detecting the drug susceptibility of Mtb to rifampicin, isoniazid and streptomycin and it only took three days. It is expected to be a new simple assay for the rapid detection of drug susceptibility of Mtb.

Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.

Ischemic stroke， an acute cerebrovascular disease caused by sudden arterial occlusion， is characterized by high morbidity， high mortality， and high disability rate. It is a major cause of the occurrence and death of neurologic diseases in the world. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a classic pathway for cellular metabolism， growth， and apoptosis. In recent years， Chinese medicine has played an important role in the treatment of ischemic stroke because of the small side effects and wide range of targets and has received extensive attention. The compound prescriptions and extracts of Chinese medicines can treat diseases via multiple targets and pathways. Researchers have extensively studied the occurrence and development of ischemic stroke and the pathophysiological mechanism of drug intervention in the treatment of ischemic stroke and have demonstrated that PI3K/Akt signaling pathway plays a key role in this process. The PI3K/Akt signaling pathway is involved in the occurrence and development of ischemic stroke by regulating pathophysiological processes such as inflammation， oxidative stress response， apoptosis， and autophagy， in which Chinese medicines play a regulatory role. This paper reviews the relationship between PI3K/Akt signaling pathway and ischemic stroke and the mechanism of Chinese medicine in treating ischemic stroke by regulating PI3K/Akt signaling pathway， aiming to provide a new theoretical basis for the clinical treatment of stroke.

Objective:To evaluate the safety and efficacy of endoscopic retrograde biliary drainage (ERBD) for acute obstructive suppurative cholangitis (AOSC) in the elderly.Methods:A retrospective analysis was performed on the clinical data of AOSC patients admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2018 to January 2020. Patients aged 75 years and over ( n=49) were assigned to the elderly group and patients under 75 years old were assigned to the control group ( n=63). General data, American Society of Anesthesiologists (ASA) grading, procedure-related indicators, incidence of postoperative complications and mortality were compared. Results:There were significant differences in age (82.6±5.1 years VS 64.6±4.5 years, t=19.98, P<0.001), albumin levels (29.1±5.9 g/L VS 34.6±8.8 g/L, t=-3.94, P<0.001) and ASA grade ( χ2=8.37, P=0.015) in the elderly group and the control group . The elderly group were accompanied by more basic diseases, i.e. hypertension [57.14% (28/49) VS 34.9% (22/63), χ2=5.51, P=0.019], coronary heart disease [55.1% (27/49) VS 27.0% (17/63), χ2=9.14, P=0.003], chronic obstructive pulmonary diseases/asthma [24.5% (12/49) VS 6.3% (4/63), χ2=7.41, P=0.006]. There were no significant differences in the operation time (31.4±8.1 min VS 30.4±8.0 min, t=-0.61, P=0.543) or hospital stay (6.1±1.7 days VS 5.7±1.4 days, t=1.35, P=0.182). The incidences of postoperative complications were 14.3% (7/49) in the elderly group and 12.7% (8/63) in the control group, showing no significant difference ( χ2=0.06, P=0.807). No ERBD-related death was observed in either group during hospital stay. Conclusion:For elderly patients with AOSC over 75 years old, emergency ERBD, which can quickly relieve the disease, is safe and effective. Advanced age is not an absolute contraindication for emergency ERBD.

Objective:To investigate the safety and feasibility of hepatectomy in the treatment of hepatic alveolar echinococcosis with secondary cavernous transformation of the portal vein.Methods:The clinical data of 7 patients undergoing surgery at the First Affiliated Hospital of Xinjiang Medical University from Jan 2010 to Dec 2019 were retrospectively analyzed.Results:There were 1 case of cavernous type Ⅰ transformation of the portal vein and 6 cases of type Ⅱ. All patients underwent partial hepatectomy. The average operation time was (9.24±4.09) h. Two patients underwent resection of cavernous segment of portal vein and reconstruction by graft, Albendazole was taken orally for 2 years after discharge. Anticoagulants were taken orally in patients with artificial vascular reconstruction. No recurrence and vascular complications were found. Five patients underwent palliative resection without resection of the cavernous segment of the portal vein. During the follow-up, cavernous transformation of the portal vein progressed in 3 patients, 2 of them esophageal varices rupture and bleeding.Conclusion:Radical hepatectomy and revascularization are the first choice for the treatment of hepatic alveolar echinococcosis complicated with secondary cavernous transformation of portal vein the result was fair.