Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2 macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.

OBJECTIVETo explore the effects of electroacupuncture (EA) on behavioral function and synaptic plasticity in hippocampal CA3 area in rats with chronic stress depression.

METHODSAccording to the random number table method, 144 SD male rats were assigned into a blank group, a model group, an EA group and a fluoxetine group, then each group was divided into a 7 d subgroup, a 14 d subgroup and a 21 d subgroup, 12 rats in each subgroup. The chronic mild unpredictable stress stimulus combined with lonely breeding were applied to establish the depression model of rats, which was performed simultaneously with intervention treatment. The rats in the EA group were treated with EA (dilatational wave) at "Shenting" (GV 24) and "Baihui" (GV 20), while the rats in fluoxetine group were treated with intragastric administration of fluoxetine, once daily. With open-field test, sugar consumption experiment and transmission electron microscope, the changes of behavior and neuronal synapse inhippocampal CA3 area were observed.

RESULTSOn 7 d, 14 d and 21 d, compared with the blank group, the open-field test score, sugar consumption and body mass were significantly lower in the model group (all<0.01); compared with the model group, the open-field test score, sugar consumption and body mass were significantly higher in the EA group and the fluoxetine group on 14 d and 21 d (<0.01,<0.05). On 14 d and 21 d, compared with the blank group, the synapse in hippocampal CA3 area was significantly lower in the model group (both<0.01); compared with the model group, the synapse in hippocampal CA3 area was significantly higher in the EA group and the fluoxetine group (<0.01,<0.05). The neurons cells in hippocampal CA3 area in the model group showed pyknosis and deformation from 7 d with fusion structure and unclear boundary of synapse, which were significantly improved on 21 d; the neurons cells in hippocampal CA3 area in the EA group and the fluoxetine group were significantly improved from 14 d and restored to normal level on 21 d, in addition, the structure of synapse restored to normal level.

CONCLUSIONSEA is involved in the regulation of synaptic plasticity in hippocampal CA3 area, and promotes the recovery of depression symptoms.

Objective To evaluate initial results of Ivor Lewis minimally invasive esophagectomy (MIE) for esophageal carcinoma using a diamond-shaped anastomosis with 45 mm linear-stapler.Methods Clinical data of 12 patients diagnosed middle to distal esophageal carcinoma and undergoing Ivor Lewis minimally invasive esophagetomy using a diamond-shaped anastomosis technique during Dec.2015 and Nov.2016 in Peking Union Medical College Hospital were collected and analyzed retrospectively.Results The mean operation time was (378 ± 56) min,the mean blood loss was (280 ± 120) ml,and the mean postoperative hospital stay was (12.2 ± 2.0) days.No positive margin,no peri-operative death occurred.Postoperative complication included atelectasis and pulmonary infection in 1 patient,paresis of left recurrent laryngeal nerve in 1 patient.No anastomotic leak or constriction occurred.Median follow up was 7 months,11 patients had no evidence of disease progress,1 patient had subcutanecous metastasis and was reoperated.Conclusion The diamond anastomosis technique utilizing in Ivor Lewis MIE for esophageal carcinoma is feasible,easy to manipulate,safe and reliable.

Objective Placental transmogrification of the lung(PTL) is rare;summarizes the reported cases and add our two cases, to explore the best diagnosis and treatment strategy.Methods Review of the cases reported in the literature, combined with the 2 cases described in this article, summarizes the characteristics of PTL and analyzed the best diagnosis and treatment strategy.Results We reported two cases of placental transmogrification of the lung, both presented in the right lower lobe, imaging performance as a giant bulla with a cystic nodule.VATS lobectomy was performed in both cases, no complication after operation.Combined with literature review of 34 cases of patients to analyze the best diagnosis and treatment strategy.Conclusion Grossly and microscopically, the lesion resembles placental tissue, with formation of placental villus-like papillary structures covered by epithelial cells.The most common imaging manifestation of PTL is a bullous emphysema pattern or with a mixed pattern of thin-walled cystic lesions and nodules.Early diagnosis and surgical operation should be performed as soon as possible, these lesions are best treated by minimally invasive surgery, leaving as much normal lung tissue and avoiding pneumonectomy if possible.Surgical treatment is usually curable and leads to successful improvement of symptoms and quality of life.

OBJECTIVETo investigate the expression and significance of miR-125a and anti-apoptotic protein Mcl-1 in intestinal tissue after massive small bowel resection in intestinal adaptation.

METHODSSprague-Dawley rats (54 male rats, 8-week old) were divided into 3 groups randomly, including two control groups. Rats in the experiment group were subjected to 70% massive small bowel resection. Rats in the resection group underwent simple intestinal resection and anastomosis. Rats in the control group underwent laparotomy alone. A 5 cm intestine approximately 1 cm distal to the anastomosis was harvested a week after operation. Expression of Mcl-1 was assessed by immunohistochemistry and real-time PCR was used to detect the expression of miR-125a in intestinal tissue.

RESULTSThe positive expression of Mcl-1 in the experiment group was 18.8%(3/16), significantly lower than that in the control group(76.5%, 13/17) and the resection group (83.33%, 15/18)(both P<0.01). The expression of miR-125a in the experiment group was 1.92, significantly higher than that in the control group (1.01) and the resection group (1.05)(both P<0.01).

CONCLUSIONmiR-125a and anti-apoptotic protein Mcl-1 may play an important role in intestinal adaptation process and they may regulate each other through a certain pathway.

Anastomosis, Surgical ; Animals ; Disease Models, Animal ; Intestine, Small ; metabolism ; surgery ; Male ; MicroRNAs ; metabolism ; Myeloid Cell Leukemia Sequence 1 Protein ; metabolism ; Rats ; Rats, Sprague-Dawley ; Short Bowel Syndrome ; metabolism

Objective To investigate the expression and significance of miR-125a and anti-apoptotic protein Mcl-1 in intestinal tissue after massive small bowel resection in intestinal adaptation. Methods Sprague-Dawley rats (54 male rats, 8-week old) were divided into 3 groups randomly, including two control groups. Rats in the experiment group were subjected to 70% massive small bowel resection. Rats in the resection group underwent simple intestinal resection and anastomosis. Rats in the control group underwent laparotomy alone. A 5 cm intestine approximately 1 cm distal to the anastomosis was harvested a week after operation. Expression of Mcl-1 was assessed by immunohistochemistry and real-time PCR was used to detect the expression of miR-125a in intestinal tissue. Results The positive expression of Mcl-1 in the experiment group was 18.8%(3/16), significantly lower than that in the control group(76.5%, 13/17) and the resection group (83.33%, 15/18)(both P<0.01). The expression of miR-125a in the experiment group was 1.92, significantly higher than that in the control group(1.01) and the resection group (1.05)(both P<0.01). Conclusion miR-125a and anti-apoptotic protein Mcl-1 may play an important role in intestinal adaptation process and they may regulate each other through a certain pathway.

Objective To investigate the expression and significance of miR-125a and anti-apoptotic protein Mcl-1 in intestinal tissue after massive small bowel resection in intestinal adaptation. Methods Sprague-Dawley rats (54 male rats, 8-week old) were divided into 3 groups randomly, including two control groups. Rats in the experiment group were subjected to 70% massive small bowel resection. Rats in the resection group underwent simple intestinal resection and anastomosis. Rats in the control group underwent laparotomy alone. A 5 cm intestine approximately 1 cm distal to the anastomosis was harvested a week after operation. Expression of Mcl-1 was assessed by immunohistochemistry and real-time PCR was used to detect the expression of miR-125a in intestinal tissue. Results The positive expression of Mcl-1 in the experiment group was 18.8%(3/16), significantly lower than that in the control group(76.5%, 13/17) and the resection group (83.33%, 15/18)(both P<0.01). The expression of miR-125a in the experiment group was 1.92, significantly higher than that in the control group(1.01) and the resection group (1.05)(both P<0.01). Conclusion miR-125a and anti-apoptotic protein Mcl-1 may play an important role in intestinal adaptation process and they may regulate each other through a certain pathway.

Objective To evaluate the relationships of the expression of orexin A in hypothalamus with hyperleptinemia, hyperinsulinism, and hyperlipidemia in alimentary obesity rats.Methods The alimentary obesity rat model was induced by high-fat diet in Wistar rats. The levels of leptin, insulin, C-peptide, total cholesterol (TC) and triglyeride (TG) were detected by luminescent immunoassay and biochemistry enzymic method. The gene expression of orexin A in rat hypothalamus was detected by real-time PCR. The correlation between orexin A and leptin was analyzed. Results After 8 weeks of high-fat diet feeding, the body weight, Lee's index, blood glucose, TG and TC significantly increased in obesity rat group (P＜0. 01). The levels of serum leptin, insulin and C-peptide were significantly higher in obesity rats than in controls [( 1.74±0. 36)μg/Lvs. (1.27±0.11) μg/L, (35±5) MIU/L vs. (23±4) MIU/L, (0.21±0.04) μg/L vs.(0. 14±0. 03) μg/L respectively, P＜0.01]. However, the level of orexin A mRNA was lower in obesity rats than in controls (6.8±2.3 vs. 14.5±3.6, t=-8.06, P＜0.01). The correlation coefficient (r) of orexin A mRNA with serum leptin, insulin, and C-peptide in alimentary obesity rat were -0. 726 (P＜0.01), -0. 506 (P＜0.01) and -0. 664 (P＜0.01), respectively. Conclusions High-fat diet can induce leptin-resistance and alimentary obesity in Wistar rat. The down-regulation of orexin A in rat hypothalamus would be correlated closely to the leptin and insulin resistance in alimentary obesity.

ObjectiveTo compare the effect of acupuncture and speech rehabilitation on motor aphasia after stroke with speech rehabilitation alone. Methods49 patients with aphasia were divided into treatment group (27 cases) and control group (22 cases) randomly. The cases in treatment group were treated with acupuncture and speech rehabilitation. The cases in control group were treated with speech rehabilitation alone. They were assessed before and 1 month, 3 months after treatment. ResultsThere was no significant difference between treatment group and control group 1 month after treatment (P>0.05), but was significant in auditory comprehension, speaking, reading, dictation and description (P<0.05) 3 months after treatment. ConclusionThe acupuncture can facilitate the recovery of motor aphas after stroke.