Farnesoid X receptor (FXR) is widely accepted as a promising target for various liver diseases; however, panels of ligands in drug development show limited clinical benefits, without a clear mechanism. Here, we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury, which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases. Upon inflammatory and apoptotic stimulation, enhanced FXR acetylation at K217, closed to the nuclear location signal, blocks its recognition by importin KPNA3, thereby preventing its nuclear import. Concomitantly, reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1, and thereby facilitating FXR export to the cytosol. Acetylation governs nucleocytoplasmic shuttling of FXR, resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP. SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation. More importantly, SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries. In conclusion, these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.

Objective To explore the preoperative localization diagnosis and surgical techniques of intractable occipital lobe epilepsy.Methods Retrospectively studied 37 patients diagnosed as occipital lobe epilepsy and underwent focal occipital resections for epilepsy.The semiology,scalp electroencephalography,MRI,fluorodeoxyglucose-positron emission tomography(FDG-PET),and intracranial EEG monitoring were used to localize the epileptogenic zones.The long-term seizure outcomes were assessed according to the Engel classification scheme.Results Visual symptoms were present in 25 patients preoperatively in this series.MRI displayed occipital lobe lesions in 15 patients,and FDG-PET revealed hypometabolism in or adjacent to epileptogenic zones.And 30 patients' epileptogenic zones and functional areas were defined by intracranial EEG monitoring.Visual field deficits were present in 35.3% of patients preoperatively,and 61% had new or aggravated visual field deficits after surgery.After a mean follow-up of 41 months,81.1% of the patients were seizure free or rarely had seizures.Conclusion The curative effect of the surgery on the medically intractable occipital lobe epilepsy is good.Intracranial EEG monitoring with electrodes extensively covering the occipital lobe and adjacent areas can be useful to demarcate the epileptogenic zones and the visural cortex,and it may prevent aggravation of the visual field deficits as much as possible.

Objective To investigate the association between the RoSCo scoring system and the postopera tive complications of laparoscopic partial nephrectomy.Methods The clinical data of 127 patients with laparoscopic partial nephrectomy in our hospital from 2010 to 2015 were retrospectively analyzed.By studying all patients' preoperative clinical data,we give all the patients the RoSCo score,then divided all the patients into the RoSCo low group (3-4),RoSCo moderate group (5-6),RoSCo high group (7-8).Respectively study the association between the RoSCo score and Clavein score,operative time,intraoperative blood loss,warm ischemia time and length of hospital stay after laparoscopic partial nephrectomy.Results The RoSCo score was associated with postoperative complications of laparoscopic partial nephrectomy (P ＜ 0.05) and was more accurate than the RENAL score alone.There were significant differences in bleeding,warm ischemia time,hospital stay and operation time between the low,middle and high groups of RoSCo (P ＜ 0.05).Conclusion The RoSCo scoring system can be used to assess the complications of laparoscopic partial nephrectomy.

Objective To evaluate the psychometric properties and the clinical feasibility of Chinese version of the Oxford Knee Score in patients with knee osteoarthritis before total knee arthroplasty.Methods One hundred and fourteen (91 females,23 males) preoperative patients with knee osteoarthritis were recruited.Internal consistency was tested using Cronbach's alpha coefficient,and dimensionality was evaluated using exploratory factor analysis.The correlations between the scale,namely,WOMAC,SF-8 and EQ-5D were used to determine construct validity.The floor and ceiling effects were also examined.Results The scale showed acceptable internal consistency (Cronbach's alpha=0.885) and demonstrated good convergent and divergent validity with the moderate to strong correlations between the scale and WOMAC (r=-0.80),the SF-8 physical component summary (r=0.65),and the EQ-5D usual activities (r=-0.41) and mobility (r=-0.35).Moreover,the strong correlation between the scale and the SF-8 mental component summary (r=0.58),as well as the moderate correlation between the scale and the EQ-5D anxiety/depression (r=-0.35) were observed.Divergent construct validity was supported by weak correlation between the scale and EQ-5D VAS (r=0.30).The exploratory factor analysis yielded three factors with eigenvalues ＞ 1,accounting for 66.02％ of the variance.All items had factor loadings above 0.4.Factor 1 closely relates to physical function,while factor 2 depicts pain associated with knee osteoarthritis.Factor 3 had only one item (item 8),reflecting the patient's sleep problems.No sign of floor or ceiling effect was found.Conclusion Chinese version of the Oxford Knee Score is proven to be a reliable,valid scale for knee osteoarthritis patients before total knee arthroplasty.

Objective To investigate the value of neuronavigation in microsurgery for medically refractory epilepsy. Methods The clinical data of 137 patients with medically refractory epilepsy who underwent epilepsy surgery with neuronavigation in our hospital from September 2008 to September 2016 were analyzed retrospectively. In these patients, 17 accepted temporal parietal occipital dissection, 23 accepted corpus callosum subtotal dissection, 11 accepted functional cerebral hemispheric dissection, and 86 accepted epilepsy foci resection. The surgical efficacies were analyzed. Results All patients uneventfully underwent the operations as planned. The mean follow-up period was 52 months (12-108 months). Engel grade I was achieved in 71 patients, grade II in 32, grade III in 25, and grade IV in 9 patients. The total satisfaction rate reached to 75.18％ (103/137), including 100％ patients (11/11) accepted functional cerebral hemispheric dissection. There were no severe operative complications. Conclusion Neuronavigation helps to locate intracranial targets, accurately resect the epileptogenic foci or disconnect the epilepsy conduction pathway, preserve the neurologic function, and avoid the operative complications.

Objective To investigate the expressions of inflammation- and fibrosis-related genes in perinephric and subcutaneous adipose tissues in patients with adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome. Methods The perinephric and subcutaneous adipose tissues adipose tissues were obtained from 8 patients with ACTH-independent Cushing's syndrome undergoing laparoscopic retroperitoneal adrenalectomy. Real-time PCR was used to detect the mRNA expression levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metallopeptidase 2 (MMP-2), TIMP metallopeptidase inhibitor 1 (TIMP-1), early growth response 1 (EGR1), CCAAT/enhancer binding protein β(CEBPβ), uncoupling protein 1(UCP-1), PPARγ coactivator 1 alpha (PGC1α) and cell death-inducing DFFA-like effector a (CIDEA). Results The mRNA level of CIDEA was significantly higher in the perinephric adipose tissue (peri-N) than in the subcutaneous adipose tissue (subQ) (P<0.05). The expressions of CEBPβ, UCP-1, and PGC1αmRNA in the peri-N were similar with those in the subQ. The expressions of IL-6, TIMP1 and EGR1 mRNA in the subQ were significantly higher than those in the peri-N (P<0.05). No significant difference in TNF-α and MMP-2 mRNA levels was found between peri-N and subQ. Conclusion The expression levels of the inflammation-and fibrosis-related genes are higher in the subQ than in the peri-N of patients with ACTH-independent Cushing's syndrome, suggesting that chronic exposure to endogenous hypercortisolism may cause adipose tissue dysfunction.

Objective To investigate the expressions of inflammation- and fibrosis-related genes in perinephric and subcutaneous adipose tissues in patients with adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome. Methods The perinephric and subcutaneous adipose tissues adipose tissues were obtained from 8 patients with ACTH-independent Cushing's syndrome undergoing laparoscopic retroperitoneal adrenalectomy. Real-time PCR was used to detect the mRNA expression levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metallopeptidase 2 (MMP-2), TIMP metallopeptidase inhibitor 1 (TIMP-1), early growth response 1 (EGR1), CCAAT/enhancer binding protein β(CEBPβ), uncoupling protein 1(UCP-1), PPARγ coactivator 1 alpha (PGC1α) and cell death-inducing DFFA-like effector a (CIDEA). Results The mRNA level of CIDEA was significantly higher in the perinephric adipose tissue (peri-N) than in the subcutaneous adipose tissue (subQ) (P<0.05). The expressions of CEBPβ, UCP-1, and PGC1αmRNA in the peri-N were similar with those in the subQ. The expressions of IL-6, TIMP1 and EGR1 mRNA in the subQ were significantly higher than those in the peri-N (P<0.05). No significant difference in TNF-α and MMP-2 mRNA levels was found between peri-N and subQ. Conclusion The expression levels of the inflammation-and fibrosis-related genes are higher in the subQ than in the peri-N of patients with ACTH-independent Cushing's syndrome, suggesting that chronic exposure to endogenous hypercortisolism may cause adipose tissue dysfunction.

Objective To investigate the different memory outcomes in temporal lobe epilepsy patients underwent different surgical approaches.Methods Two hundred forty-eight patients with temporal lobe epilepsy and hippocampal scle-rosis underwent standard anterior temporal lobectomy ( ATL, n=83 ) or selective amygdalohippocampectomy ( SAH, n=165) from 2009 to 2013.All the patients underwent clinical memory function assessment before surgery, 3 months and 2 years after surgery respectively.Results The memory quotient ( MQ) of patients who underwent brain surgery in the domi-nant hemisphere significantly decreased 3 months after surgery (74.5 ±16.2, 75.6 ±19.5) compared to presurgery MQ (82.9 ±15.8, 83.2 ±21.2) in both ATL and SAH groups (P<0.05).Although MQ was slightly recovered at 2 years af-ter surgery, MQ (75.1 ±14.1, 76.1 ±17.6) was still significantly lower compared with presurgery MQ (P<0.05).A-mong this, both the decrease extent of the MQ 3 months after surgery and 2 years after surgery were smaller in the SAH group than in the ATL group (7.6 vs.8.4;7.1 vs.7.8).The MQ of patients who underwent brain surgery in the non-dominant hemisphere (either ATL or SAH ) increased slightly 3 months after surgery (87.2 ±15.1, 88.1 ±16.9) com-pared to presurgery MQ (85.5 ±13.5, 85.3 ±19.7) although the difference was not statistically significant.The MQ of these two groups improved significantly 2 years after surgery (92.8 ±12.7, 93.7 ±17.1)(P<0.05).The improvement extent of the MQ was larger in the SAH group than in the ATL group (8.4 vs.7.3).Conclusions SAH may be better than ATL in the maintenance of memory function in patients with temporal lobe epilepsy and hippocampal sclerosis.

Objective To investigate the morphological characteristics of superior sagittal sinus (SSS) and bridging vein (BrV) with virtual reality (VR) technology and their clinical significances.Methods Forty-three patients with parasagittal meningioma (PSM group) and 21 patients with trigeminal neuralgia or hemifacial spasm who had no intracranial venous system diseases (normal group),admitted to our hospital from October 2011 to March 2013,were chosen.The morphological characteristics of SSS and parasagittal BrV of patients from the 2 groups were observed,which was finished in the VR workstation.The number and diameter differences of cortical veins between the 2 groups,and bilatelal side and the first,middle and third 1/3 of SSS of normal group were analyzed.Results Among the patients from the 2 groups,4 having SSS extremity with morphological variation were observed firstly.The direction of BrV entering the SSS mainly was retrograde,which concentrated in the middle and third 1/3 of SSS.There were many directions of BrV entering the SSS in the first 1/3 of SSS,and the direction mostly was perpendicular.In normal group,there were no statistical differences of number and diameter in the bilatelal cortical veins (P＞0.05); in the first,middle and third 1/3 of SSS,there was statistical difference of cortical veins number (P＜0.05),but no difference of diameter (P＞0.05).The number and diameter of cortical veins of PSM group were under the normal group,with statistically significant difference (P＜0.05).With the growth of PSM,violations of SSS and cortical venous gradually aggravated,affecting venous return,which resulted in increase number and complication of collateral veins.Conclusions There is certain variability of SSS and related BrV.The direction of BrV entering the SSS may be associated with intracranial venous system hemodynamic.It is clear and three-dimensional to observe SSS and cortical veins in the help of VR,and to analyze the venous circulation changes caused by PSM.

OBJECTIVETo evaluate the factors affecting the efficacy of extracorporeal shock wave lithotripsy (ESWL) and establish a model for predicting the success rate of a single ESWL session in the treatment of single renal calculus.

METHODSBetween January 2008 and February 2010, 325 patients underwent ESWL monotherapy and were followed up for at most 3 months. The correlations between the outcome of a single ESWL session and the patients' age, gender, body mass index (BMI), disease duration, pretreatment renal colic, hematuria, urinary irritation symptoms, stone location, stone laterality, stone length and stone width were analyzed. The statistically significant factors identifies were further analyzed by multivariate logistic regression, and the predictive model was established.

RESULTSThe stone-free rate of ESWL was 76.9%. Univariate analysis found that the patients' age, stone laterality, stone location, disease duration, pretreatment hematuria, stone length and width all significantly affected the outcome of the treatment. Logistic regression analysis indicated the factors including disease duration, pretreatment hematuria, stone length and stone width determined the success rate of the treatment. Hosmer and Lemeshow Test showed a good fitting of the predictive model (Χ(2)=18.144, df=8, P=0.168) with an overall accuracy of 87.4%.

CONCLUSIONDisease duration, pretreatment hematuria, stone length and width are independent factors affecting the outcome of a single ESWL session for single renal calculus.

Adult ; Female ; Humans ; Kidney Calculi ; therapy ; Lithotripsy ; Logistic Models ; Male ; Middle Aged ; Treatment Outcome