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.

BACKGROUND:Combined radiation and wound injury appeared mainly in patients with tumor radiotherapy and nuclear radiation accidents.The radiation destroys the repair mechanism,resulting in delayed or prolonged wound healing.It still lacks an effective therapeutic strategy currently. OBJECTIVE:To prepare multifunctional wound dressings based on the multiple clinical symptoms of combined radiation and wound injury,which are designed to be antibacteria,promoted healing and analgesics. METHODS:Using levofloxacin,fibroin and lidocaine hydrochloride as raw materials,3D bioprinting technology was applied to prepare the multifunctional wound dressing.(1)The multifunctional dressing was placed on a fixed culture plate coated with Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa,and incubated at 37 ℃ overnight to detect the diameter of the antibacterial zone.(2)40 Kunming mice were randomly divided into trauma group,radiation and trauma model group,treatment group and positive drug group,with 10 mice in each group.Mice in the radiation and trauma model group,treatment group and positive drug group were irradiated by 60Co gamma rays.After 1 hour of radiation,a full-layer skin defect wound with a diameter of 1 cm was made on the back of each mouse in the four groups.Normal saline was applied to the wounds of the trauma group and the radiation and trauma model group.Trethanolamine cream was applied to the wounds of the positive drug group.Multifunctional dressing was applied to the wounds of the treatment group.The dressing was changed every 2 days,and the treatment was continued for 14 days.Wound healing rate and serum interleukin-6 level were measured at 3,7 and 14 days after wound modeling.14 days after the wound modeling,the skin tissue of the wound was obtained and received hematoxylin-eosin staining,Masson staining and cytokeratin-14 immunohistochemical staining. RESULTS AND CONCLUSION:(1)3D-printed multifunctional wound dressing had good antibacterial activity.The antibacterial zone diameters against Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa were(4.15±0.09),(4.18±0.23)and(4.35±0.13)cm,respectively.(2)With the extension of modeling time,the wound healed gradually.The wound healing rate of the treatment group and the positive drug group was higher than that of the radiation and trauma model group at 3,7 and 14 days after modeling(P<0.01,P<0.001).The wound healing rate of the treatment group was higher than that of the positive drug group.With the extension of modeling time,the serum interleukin level of mice increased first and then decreased.The serum interleukin level in the treatment group at 3,7 and 14 days after modeling was lower than that in the radiation and trauma model group.Hematoxylin-eosin staining and Masson staining exhibited that inflammatory cells infiltrated the granuloma tissue in the trauma group,and the dermal collagen fibers were densely arranged.The normal structure of epidermis and dermis was destroyed and inflammatory cells were infiltrated in the radiation and trauma model group.In the treatment group,normal skin mucosal tissue was observed,the epidermis was arranged closely,and the sweat glands,hair follicles and dermal collagen fibers were arranged regularly.In the positive drug group,the arrangement of epidermal layer was tight,and the arrangement of sweat glands,hair follicles and dermal collagen fibers was regular.Cytokeratin-14 immunohistochemical staining displayed that the epidermal tissue thickness in the treatment group was lower than that in the other three groups(P<0.01,P<0.001).(3)The results confirm that the 3D-printed multifunctional dressing has multiple functions of local anesthesia,anti-infection and promoting healing.

Objective:To assess the efficacy of different modes of high-flow nasal cannula (HFNC) oxygen therapy modes in preventing hypoxaemia during general anesthesia in obese patients without endotracheal intubation.Methods:Eighty-four American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-64 yr, with body mass index ≥ 30 kg/m 2, undergoing non-intubated general anesthesia surgery, were divided into 3 groups ( n=28 each) by a random number table method: nasal cannula oxygen therapy group (NC group), HFNC oxygen therapy full-course non-pure oxygen group (HFNC1 group) and HFNC oxygen therapy half-course non-pure oxygen group (NHFC2 group). NC group received oxygen through bilateral nasal cannula, and the oxygen flow rate was 5 L/min, and the oxygen flow rate remained unchanged after anesthesia induction. In NHFC1 group, the flow rate was 30 L/min and the FiO 2 was 41%, and the flow rate was adjusted to 60 L/min after anesthesia induction, and the FiO 2 remained unchanged. NHFC2 group received HFNC oxygen inhalation with a flow rate of 30 L/min and FiO 2 100%, and the flow rate was adjusted to 60 L/min and FiO 2 41% after anesthesia induction. Sufentanil 0.1 μg/kg was intravenously injected after 3 min of oxygen pre-inhalation and target effect-site concentration of propofol was 4 μg/ml in open-loop TCI mode, the closed-loop mode was used to continue intravenous infusion of propofol when the BIS value reached 60 with the same target effect-site concentration, and the intraoperative BIS value was maintained at 45-60. The occurrence and total duration of hypoxemia (SpO 2 <92%) and the lowest value of SpO 2 during anesthesia were recorded. Arterial blood gas analysis was performed before anesthesia induction, at 3 min of oxygen pre-inhalation and at 10 min after anesthesia, and PaO 2 and PaCO 2 were recorded. Respiratory interventions and adverse events were recorded. Results:One patient was excluded due to change of anesthesion method in NC group.Compared with NC group, the incidence of hypoxemia was significantly decreased, the total duration of hypoxemia was shortened, the lowest value of SpO 2 was increased, and the usage rate of respiratory intervention methods was decreased, and PaO 2 was increased and PaCO 2 was decreased at 3 min of oxygen pre-inhalation and 10 min after anesthesia in HFNC2 group ( P<0.05), and PaCO 2 was significantly decreased at 3 min of oxygen pre-inhalation, PaO 2 was increased and PaCO 2 was decreased at 10 min after anesthesia ( P<0.05), and no significant change was found in the other parameters in HFNC1 group ( P>0.05). Compared with HFNC1 group, the incidence of hypoxemia was significantly decreased, the total duration of hypoxemia was shortened, the lowest value of SpO 2 was increased, the usage rate of respiratory intervention methods was decreased, and PaO 2 was increased at 3 min of oxygen pre-inhalation in HFNC2 group ( P<0.05). There was no significant difference in adverse events between the three groups ( P>0.05). Conclusions:HFNC in the mode of FiO 2 100% during oxygen pre-inhalation and FiO 2 41% during anesthesia maintenance can reduce the occurrence of hypoxemia during general anesthesia in obese patients without intubation.

Objective:To evaluate the safety and efficacy of eltrombopag combined with immunosuppressive therapy in patients with aplastic anemia (AA) in China.Methods:We investigated and analyzed the clinical data of AA patients from 14 hematological treatment centers who were treated with oral eltrombopag for at least 3 mon.Results:We enrolled 56 AA patients, including 19 treatment-na?ve patients and 37 IST-refractory patients. The median administration period for eltrombopag was 7 (3-31) months, and the median maximum stable dosage was 75 mg/d (50-150 mg/d) . The 3-month hematological response (HR) rate was 60%, and the complete response (CR) rate was 30% in 10 SAA patients who were treated with first-line eltrombopag and standard IST (ATG+CsA) . Eight of 9 eltrombopag and CsA ± androgen first-line treated SAA patients responded (8/9, 89%) and 4 (44%) gave CR. The overall HR and CR rates were 79% and 52.6%, respectively, among these 19 patients by the end of the follow-up period. Of the 19 AA patients who were refractory to CsA ± androgen, 11 achieved HR (57.9%) at 3 mon, and the best HR rate was 44% in standard IST (ATG+CsA) refractory 18 patients after eltrombopag treatment. Fifty-one percent of the patients experienced mild or moderate adverse events, and gastrointestinal discomfort was the most common adverse effect reported by the study subjects.Conclusion:Adding Eltrombopag in first-line IST can accelerate the acquisition and improve the quality of hematological responses in AA patients. AA with relatively more residual hematopoietic cells may be well treated with eltrombopag and non-ATG IST. Eltrombopag can be used as salvage therapy for CsA±androgen refractory patients. Eltrombopag was generally safe and well tolerated by AA patients in China.

Objective To evaluate the effect of electroacupuncture on postoperative cognitive func?tion in elderly patients undergoing carotid endarterectomy. Methods Fifty patients of both sexes, aged≥65 yr, of American Society of Anesthesiologists physical status Ⅱ orⅢ, with the educational level≥ the level of primary school, scheduled for elective unilateral carotid endarterectomy, were divided into 2 groups ( n=25 each) using a random number table: control group ( group C) and electroacupuncture group ( group EA). In group EA, electroacupuncture (frequency 2∕100 Hz, intensity 5-12 mA) of Baihui (GV20), Neiguan (PC6) and Zusanli (ST36) was performed throughout surgery starting from 30 min before opera?tion, and then general anesthesia was performed. General anesthesia was performed directly in group C. Before operation ( T0 ) , at the end of operation ( T1 ) and at 24 h after operation ( T2 ) , blood samples were collected from the internal jugular vein for determination of plasma S?100βprotein, tumor necrosis factor?αand brain?derived neurotrophic factor ( BDNF) concentrations by enzyme?linked immunosorbent assay. The cognitive function was assessed using Montreal Cognitive Assessment at T0,2 and at 3 and 7 days after opera?tion ( T3,4 ) . Results Compared with group C, the Montreal Cognitive Assessment scores were significantly increased at T2?4 , the plasma S?100β protein and tumor necrosis factor?α concentrations were significantly decreased at T1,2 , and the plasma BDNF concentrations were significantly increased at T2 in group EA ( P<0?05) . Conclusion Electroacupuncture can improve postoperative cognitive function in the elderly pa?tients undergoing carotid endarterectomy, which may be related to inhibition of inflammatory responses,
promotion of BDNF production and reduction of brain injury.

Objective:To construct double-layered controlled release system containing SDF-1 and rhBMP-2 molecules and to study the release profile of the system in vitro.Methods:The polylactic acid/chitosan(PLA/CS)nanoparticles were prepared with “emulsification-solution evaporation method”,the preparation parameters were determined by orthogonal test design.The particle size was observed by nanoparticle size analyzer,the morphology of the nanoparticles was observed with electron microscope.Then rhBMP-2 and SDF-1 were loaded into the nanoparticles in the process of emulsification,the loading efficiency and encapsulation efficiency were calculated and in vitro release was observed.Results:The double-layer nanoparticles showed spherical geometry,smooth surface and complete separation. The average particle size of the nanoparticles was (542.33 ±14.38)nm;The drug loading and incorporation efficiency of rhBMP-2 were (82.41 ±1.05)% and (24.67 ±0.43)ng/mg,those of rhBMP-2 were (75.58 ±0.84)% and (22.63 ±0.41)ng/mg,respectively. The release time of the drug from the system sustained over at least 30 days,the release profile of both drugs showed “biphasic release”. The cumulative release rate of SDF-1 and rhBMP-2 was 72.85% and 91.01% in 30 days respectively.Conclusion:The SDF-1 and rh-BMP-2 loaded PLA/CS nanoparticles have excellent morphology,high entrapment and good sustained-release in vitro.

According to the characteristics of minor students majored in clinical anesthesia, an objective structured clinical examination (OSCE) program was established. This OSCE was applied to clinical anesthesia minor students for departmental rotation examination. Meanwhile, a questionnaire was set to collect students' attitude towards the OSCE assessment program. Results showed that OSCE assessment program could objectively and comprehensively reflect the students' clinical skills. Students participated in OSCE were quite satisfied with its design, organization, quality and effectiveness.

Objective To discuss the therapy for acetabular comminuted fractur e combined with compressive defects. Methods From July 1997 to February 2005, 43 cases of comminuted acetabular fracture combined with compressive defect were t reated. 25 cases were obsolete, 16 fresh, and 2 malformed (90 days after injury) . 34 cases were complicated fractures with defects, and 9 simple fractures with defects. The defect volumes ranged from 3 to 9 cm3, averaging 4.5 cm3. They were treated with ATMFS (acetabular tridimensional memory fixation system) to fixate the comminuted bone fragments tridimensionally. The modified acetabular approac h, reduction of acetabular comminuted articular face, anatomical reconstruction of posterior wall of acetabulum with autogenous ilium, autogenous and artificial bone implantation and bone wax isolation were used. The follow-ups lasted from 5 to 86 months, averaging 15.7 months. Results 31 cases achieved anatomical red uction by filling up the compressive defects. 12 cases were treated by anatomica l reconstruction of posterior wall. On average, 5.3 months after operation, the injured hip joint was as good as the healthy one in 40 cases. Ischemia necrosis of femoral head occurred in 1 case, and 2 cases experienced heterotopic ossifica tion with ischemia necrosis of femoral head which led to osseous fusion of hip j oint. Conclusion The new methods for treatment of acetabular fractures with comp ressive defects elevate the reduction rate of acetabulum and femoral head, and a re effective for the functional recovery of hip joint.