Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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AIM:To investigate the effects of ubiquitin-specific peptidase 9, X-linked (USP9X) down-regula-tion on apoptosis and invasion ability in gastric carcinoma cells, and to explore its possible molecular mechanisms. METH-ODS:USP9X small interfering RNA (siRNA) and control siRNA were used to be transfected into gastric carcinoma AGS cells. The cells were divided into 3 groups, including untreated AGS group, control siRNA group and USP9X siRNA group. The expression of USP9X at mRNA and protein levels in the AGS cells with different treatments was determined by real-time PCR and Western blot. The cell viability was analyzed by CCK-8 assay. Flow cytometry and Boyden chamber were employed to examine the apoptosis and invasion ability of the AGS cells. RESULTS:USP9X siRNA significantly down-regulated the expression of USP9X at mRNA and protein levels in the AGS cells. Down-regulation of USP9X markedly induced apoptosis and reduced invasion ability of the gastric carcinoma AGS cells. Notably, down-regulation of USP9X sig-nificantly reduced the protein expression of Mcl-1 and MMP-2, but markedly increased the protein level of Bax. CON-CLUSION:USP9X may be a key regulator for apoptosis and invasion in gastric carcinoma.

Objective To observe the influence of spinal cord injury on lower limbs weight support capacity,and the changes with time. Methods Six adult female rhesus monkeys with thoracic(T7-9)right spinal cord hemi-section were measured the plantar pressure ratio of both lower limbs with Foot-Scan system before,and six and twelve weeks after operation. Results There was no statistical difference between both sides of limbs before operation(Z=-1.330,P>0.05),while the plantar pressure ratio was more on the left limbs six and twelve weeks after operation(Z>4.783,P<0.001).The plantar pressure ratio of right lower limb became less and less during observation(Z=3.191,P<0.001). Conclusion The weight support capacity of affected limbs is injured after spinal cord hemi-section in monkeys, and would become worse without intervention.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; therapy ; Peripheral Blood Stem Cell Transplantation ; Prognosis ; Retrospective Studies ; Transplantation, Autologous ; Treatment Outcome

BACKGROUNDThe gender difference on long-term outcome in unselected patients after percutaneous coronary intervention (PCI) has not yet been fully investigated. This study aimed to evaluate the gender difference on five-year outcomes following EXCEL biodegradable polymer-coated sirolimus-eluting stenting in patients with coronary disease.

METHODSA total of 2077 "all comers", consisting of 1528 (73.6%) men and 549 (26.4%) women, who were exclusively treated with EXCEL coronary stents were enrolled in the prospective CREATE study at 59 centers from four countries. After propensity score matching, the baseline characteristics of the two groups were well matched. Recommended antiplatelet regimen was clopidogrel and aspirin for six months followed by chronic aspirin therapy. The primary outcome that was the rate of major adverse cardiac events (MACE), defined as a composite of cardiac mortality, non-fatal myocardial infarction (MI) and target lesion revascularization (TLR), and stent thrombosis (ST) at five years were compared between the two gender groups.

RESULTSIn the two groups, women had higher proportions of clinical risk factors, such as being elderly, diabetes mellitus, hypertension and hyperlipidemia, compared to men. Besides, the mean target vessel number per patient was higher and the mean reference vessel diameter smaller for women. Men had higher risks of cardiac death (3.7% vs. 1.6%, P = 0.021) and MACE (8.4% vs. 4.7%, P = 0.004) at five years compared with women. However, the cumulative hazards of non-fatal MI and TLR were similar between men and women. The incidence of Academic Research Consortium (ARC) definite or probable stent thrombosis was similar between the two groups (1.3% vs. 1.0%, P = 0.639). Prolonged clopidogrel therapy (>6 months) did not reduce the cumulative hazards of ST from six months to five years in both men (χ(2) = 0.098, log rank P = 0.754) and women (χ(2) = 2.043, log rank P = 0.153) patients.

CONCLUSIONSWomen had a lower MACE and cardiac death rate than men after biodegradable polymer-coated sirolimus-eluting stenting in long term follow-up. Effects of prolonged dual antiplatelet therapy (DAPT) in preventing stent thrombosis was similar with six-month DAPT after EXCEL stent implantation in both men and women groups.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Polymers ; chemistry ; Prospective Studies ; Sex Factors ; Sirolimus ; therapeutic use ; Treatment Outcome

OBJECTIVETo explore the therapeutic effect and safety of fire needling on rat with rheumatoid arthritis.

METHODSForty female Wistar rats were randomly divided into a normal group, a model group, a methotrexate (MTX) group and a fire needling group, 10 rats in each group. The 0.1 mL of normal saline was subcutaneously injected in rat's right back paw in the normal group, while the other groups received subcutaneous injection of 0.1 mL of complete Freund's adjuvant to establish the model. The pricking method was applied in the fire needling group at "Jiaji" (EX-B 2), "Zusanli" (ST 36) and Ashi points with a depth of 5 mm, once every three days, and totally eight times were required. In the MTX group, with intragastric administration of 2.0 mg/kg per rat, the treatment was given once every seven days, and totally four times were required. The weight, swelling rate of foot, joint pain score and polyarthritis index of rats in each group as well as the pathological change of liver tissue under light microscope were observed.

RESULTSThe weight, swelling rate of foot, joint pain score and polyarthritis index in the model group were significantly higher than those in the normal group (P < 0.05, P < 0.01), after the treatment, the above-mentioned indexes in the two treatment groups were obviouly dereased as componed with those in the model group (all P < 0.01), and there were statistical differences between the fire needling group and MTX group (P < 0.05, P < 0.01). Compared with the normal group, inflammatory cells were appeared with a cluster distribution in the liver cells of rats in the model group. The inflammatory cells were reduced in the MTX group and fire needling group, and liver cells had degenerative edema and cell nucleus were largen and deformed in the MTX group.

CONCLUSIONThe fire needling has significant efficacy for rats with adjuvant arthritis (AA) without any damage to the liver, which coud have a better control of disease progression of rheumatoid arthritis .

Acupuncture Therapy ; adverse effects ; instrumentation ; methods ; Animals ; Arthritis, Rheumatoid ; therapy ; Female ; Humans ; Rats ; Rats, Wistar

OBJECTIVETo explore the effectivity and safety of single high-dose (HD) etoposide (Vp16) with granulocyte colony-stimulating factor (G-CSF) for mobilization of autologous peripheral blood stem cells (PBSC) in patients with hematologic malignancies.

METHODS80 patients of hematologic malignancies including 20 patients with acute leukemia (AL), 23 with multiple myeloma (MM), 35 with non-Hodgkin's lymphoma (NHL) and 2 with Hodgkin's lymphoma (HL) received Vp16 (1.6 g/m(2)) continuous intravenous infusion for 10 hrs on day 1. G-CSF at 10 µg/kg once daily subcutaneous injection began to use on day of ANC lower than 1×10(9)/L and continued until PBSC collection was completed. Autologous PBSC (APBSC) was collected on day of WBC greater than 5×10(9)/L and continuing until the collection goal was met (target value: MNC ≥ 6.0×10(8)/kg and CD34(+) ≥ 2.0×10(6)/kg). The patients received APBSC after conditioning regimen. The number of the cells collection, time of hematopoietic reconstruction, adverse effect and so on were observed during the course of stem cell mobilization and collection.

RESULTSPBSC was collected on day 11 (range: 7 - 25 days) of after Vp16 administration with a median collection time of 2 (range 1 - 5). 3/80 patients with AML got stem cell mobilization failure. 5 of 6 patients who failed to mobilize before got successful stem cell mobilization, 1/6 patient with AML-M(5) got a second failure after the mobilization of VP16 whose first time's mobilization using Ara-C did not succeed. The median number of CD34(+) cells collected in 77 patients who got successful mobilization was 4×10(6)/kg \[range (1.59 - 24.68)×10(6)/kg\]. The collection of 20 patients with AL and 23 with MM were got detection for minimal residual disease, no pollution of tumor cells were happened. All patients could tolerate the whole course of stem cell mobilization. 29/80 (36.25%) patients got a 4 grade leucopenia, 19/80 (23.75%) patients got infection.

CONCLUSIONSingle high-dose etoposide with G-CSF for mobilization of APBSC has a higher achievement ratio, a controllable adverse effect, a promising hematopoiesis recovery, which is an effective and safe mobilizing regimen for patients with hematologic malignancies.

Adolescent ; Adult ; Aged ; Etoposide ; administration & dosage ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Hematologic Neoplasms ; Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Young Adult

This study was purposed to investigate the incidence of mixed lineage leukemia (MLL) gene rearrangement and partner gene types as well as the clinical features and prognosis of acute leukemia (AL) with this rearrangement through detection in adult AL using combination of 3 techniques, and to evaluate the clinical value of this combination detection. The MLL gene rearrangement in 183 cases of adult AL was detected by combination of conventional cytogenetics, split signal FISH and multiplex nested PCR. The results showed that the incidence of MLL rearrangements in adult patients with AL was low (8.2%), and MLL-AF4 fusion gene was most common and predominant in acute lymphoblastic leukemia (ALL), while the MLL-AF6 and MLL-AF9 were most frequent in acute myeloid leukemia (AML). Extramedullary involvements were found in 40% of MLL-rearranged AL patients, and 33.3% of patients with MLL-rearranged AL reached to complete remission within 30 days during induction chemotherapy. In addition, in this cohort of MLL-rearranged adult AL patients, the 3-month relapse rate and 6-month overall survival rate were 50.0% and 50.0% respectively. It is concluded that the rate of missed diagnosis of CC technique for patients with MLL-rearranged AL reached to 60% in this study, while the combination of CC, FISH and multiplex nested PCR has been confirmed to have important significance for evaluating prognosis and conducting clinical therapy of patients with MLL-rearranged AL.
Adolescent ; Adult ; Aged ; Female ; Gene Rearrangement ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Oncogene Proteins, Fusion ; genetics ; Young Adult