ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Objective:To explore the changes of large-scale functional brain networks and network topological properties in patients with major depressive disorder (MDD) whose diagnosis had not changed after 5 years of follow-up.Methods:Totally 521 cases of hospitalized MDD patients were recruited from January 2012 to August 2018, and another 204 cases of gender- and age-matched healthy controls were recruited. All participants completed resting-state functional magnetic resonance scanning and clinical assessment. Their diagnosis were reviewed 5 years after discharge.A total of 258 participants whose diagnosis had not changed were counted into the MDD group for analysis. The differences in large-scale brain network connectivity between the two groups were analyzed by constructing a whole-brain functional network, on the basis of which the altered topological properties of the sensorimotor network (SMN), visual network (VN) and default mode network (DMN) were further analyzed between the two groups.The SPSS 24.0 software was used for data analysis and the independent sample t-test and χ2 test were used for the data comparison of the two groups. Results:Compared with the healthy controls, the MDD group had significantly decreased network clustering, mainly involving the SMN, VN and DMN (edge P<0.001, cluster P<0.05). The MDD group had decreased functional connectivity(FC) strength within the SMN, VN and DMN networks, the FC strength between the SMN and VN networks, between the frontoparietal network (FPN) and the DAN networks were decreased(all P<0.05, FDR corrected). Graph-theory analysis showed that local efficiency, clustering coefficient, and normalized shortest path length were decreased in the MDD group, node efficiency was decreased in the left ventral medial prefrontal cortex and the middle of the bilateral insula, node centrality was decreased in the middle of the bilateral insula and occipital lobe, and the betweenness was decreased in the middle of the right insula (all P<0.05, FDR corrected). Conclusion:MDD exhibits abnormal network functional connectivity, disruption of network topological properties, diminished optimal information processing, and to some extent reflects the severity of depressive symptoms. The decreased ability of information transfer flow in the insula plays an important role for the functional abnormality of the network.

Objective:To explore the difference of gray matter volume between anxious depression(AD)and non anxious depression(NAD) patients, and its correlation with clinical characteristics.Methods:One hundred and fifty patients with depression were included from September 2014 to October 2018, meanwhile 62 healthy controls with matching demographic characteristic were recruited. The severity of the patients was assessed by Hamilton depression scale-17(HAMD-17). Patients were divided into anxious depression group(AD group, n=80)and non-anxious depression group (NAD group, n=70) according to whether anxiety/somatization factor scored 7. All subjects were scanned with 3.0 T underwent structural MRI scan. The structural magnetic resonance data were preprocessed by voxel-based morphometry (VBM). The rest toolkit was used to calculate the difference of gray matter volume among the three groups. By SPSS 19.0, post-hoc t test was used for pairwise comparison and Pearson correlation analysis was performed between gray matter volume and clinical factors in patients with anxious depression. Results:Compared to the NAD group, the gray matter volume of the right middle frontal gyrus(MNI: x=28.5, y=21.0, z=48.0, t=-4.83, Bonferroni multiple comparison adjustment, P<0.05/3) and left dorsolateral superior frontal gyrus(MNI: x=-18.0, y=27.0, z=43.5, t=-6.08, Bonferroni multiple comparison correction, P<0.05/3)were significantly decreased in AD group. Correlation analysis found that the gray matter volume of the right middle frontal gyrus in patients with anxious depression was negatively correlated with the insight of anxiety/somatization factor score ( r=-0.36, P=0.001). Conclusion:The volume of prefrontal lobe in patients with anxiety depression is lower than that in patients with non anxiety depression, which may be related to the serious clinical symptoms in patients with anxiety depression.The decrease of right middle frontal gyrus volume can be used as a potential biological marker for the severity of impaired insight.

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Adenosine Triphosphate ; Animals ; Chemical and Drug Induced Liver Injury/etiology* ; Flavonoids ; Humans ; Inflammasomes ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nigericin

Objective To explore the influence of rs1360780 T risk allele of FK506-binding protein 5 (FKBP5) gene on the brain function under resting-state and its association with clinical symptoms as well as immune function in patients with major depressive disorder (MDD).Methods Totally 147 MDD patients and 61 gender-,age-,and education-matched healthy controls were scanned with 3.0T MRI Scanner and genotyped.The peripheral serum immunoglobulin and complement were measured.The main effect of the disease,the genotype and their interaction effects were analyzed using regional homogeneity (ReHo) by two-way ANOVA.Abnormal brain activity was identified in T risk allele carriers of rs1360780 and non-risk CC individuals in MDD using post hoc analyses.Correlation analyses were performed between ReHo values of significant brain regions and the total score,five-factor scores of Hamilton rating scale for depression (HAMD-17),serum levels of immunoglobulin and plasma complement component in MDD patients.Results (1) The results of 2x 2 ANOVA showed the interaction effects located in the left opercular part of inferior frontal gyrus (MNI:x,y,z =-42,6,9;F=10.83),right opercular part of inferior frontal gyrus (MNI:x,y,z =30,6,33;F=15.05),left medial superior frontal gyrus (MNI:x,y,z=-9,54,0;F=9.17) and left pallidum (MNI:x,y,z =-12,6,-6;F=11.37) (Alphasim corrected,P＜ 0.05).(2) In post-hoc analyses for the main effect of genotype,T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI:x,y,z=60,12,6;t=2.88) compared with CC carriers;for the effect of diseaseby-genotype interaction,T+ carriers with MDD showed increased ReHo values in the right opercular part of inferior frontal gyrus (MNI:x,y,z=30,6,33;t=2.96) and decreased ReHo values in the left orbital part of inferior frontal gyrus (MNI:x,y,z =-21,9,-18;t =-3.21) (Alphasim corrected,P＜ 0.05) in contrast to CC carriers.(3)Pearson's correlation showed that the average ReHo values of the right opercular part of inferior frontal gyrus negatively correlated with the content of immunoglobulin G (r=-0.528,P=O.0016,Bonferroni corrected) and positively correlated with anxiety/somatization factor score (r=0.421,P＜0.001,Bonferroni corrected) in T + carrìers with MDD.Conclusion The results of this study suggest that rs1360780 T-risk allele of FKBP5 gene is involved in the changes of local neural activity in the right opercular part of inferior frontal gyrus of depressed patients and could potentially indicate a neuropathological mechanism of anxiety somatic symptoms and immune dysfunction in depression.

Objective: To explore the safety and feasibility of transumbilical single channel laparoscopic cryptorchidopexy with conventional instruments in treatment of cryptorchidism in children. Methods: Thirty-five children with cryptorchidism were treated by transumbilical single channel laparoscopic cryptorchidopexy with conventional instruments from November 2017 to March 2018 at Department of Pediatric Surgery, the First Affiliated Hospital of Guangxi Medical University.Clinical data were recorded including the general information, operation time, intraoperative blood loss, postoperative testicular position and postoperative complications, etc. Results: All 35 patients completed the cryptorchidopexy in one operation.Among those 35 patients, 28 patients had unilateral lesions and 7 patients had bilateral lesions, with a total of 42 sides.Twenty-six patients were of groin type(33 sides), 9 patients abdominal type(9 sides). The average operation time was (40.4±8.2) min for unilateral lesion, and (62.5±15.3) min for bilateral lesions; the average intraoperative blood loss was (3.0±1.8) mL; and the average postoperative hospital stay was (6.4±2.1) h. Testis of 32 patients (40 sides) were fixed in the middle and bottoms of the scrotum, and testis of 2 patients (2 sides) were fixed on the top of the scrotum.One case had poor healing of naval incision, which was recovered in 1 week after dressing change.There were no postoperative complications such as scrotum hematoma, infection of incision, testicular epididymitis, testicular necrosis, testicular retraction or testicular atrophy, etc.No obvious visible scar was found in the abdomen review 2 weeks postoperatively, with the incidence of complications was 2.9%(1/35 cases). Conclusions Transumbilical single channel laparoscopic cryptorchidopexy with conventional instruments in treatment of cryptorchidism is characterized by small trauma, quick recovery, low complication rate and visible scar free result, which is worthy of clinical promotion, but the operation is relatively complex and the correct procedures are required.

Objective To explore the role of functional connectivity( FC) between the subgenual anterior cingulate cortes(sgACC) and limbic cortices in predicting the efficacy of early antidepressant treat-ment. Methods Resting state magnetoencephalography( MEG) data were collected from 32 patients with major depressive disorder(MDD) and 20 matched healthy control subjects at baseline.According to whether the HAMD17total score reduction rate reached 50% after 2 weeks,the patients were divided into responder group and non-responder group.The difference of the FC,the relationship between the FC and the change rate of HAMD17were explored. Results Compared with controls,MDD patients showed decreased connectivity of the sgACC with the right hippocampus(MNI coordinate:x＝30,y＝－3,z＝－24; F＝5.11,P＝0.028),the right amygdala(MNI coordinate:x＝22,y＝－2,z＝－15; F＝6.90,P＝0.012) and the left amygdala(MNI coordi- nate:x＝－24,y＝－6,z＝－16; F＝5.75,P＝0.020).Compared with non-responders,the connectivity of the sgACC with the right hippocampus(MNI coordinate:x＝30,y＝－3,z＝－24;F＝8.74,P＝0.0065),the right a-mygdala(MNI coordinate:x＝22,y＝－2,z＝－15; F＝12.417,P＝0.0016) were higher in responders.Pretreat-ment connectivity of the sgACC with the right hippocampus(r＝－0.50,P＝0.0066),the right amygdala(r＝－0.56,P＝0.0018) were negatively correlated with clinical improvement.ROC analyses confirmed the value of the connectivity of sgACC with the right hippocampus(area under curve(AUC)＝0.71,P＝0.042),the right amygdala(AUC＝0.73,P＝0.029) in classifying responders versus non-responders in 2 weeks of treatment. Conclusion The decreased FC of the sgACC with the right hippocampus and the right amygdala at baseline is associated with a better improvement,which can potentially serve as a treatment outcome biomarker in ear-ly curative effect of depression.

Objective To explore the energy feature of the spontaneous neural activity in depressive patients with diurnal rhythm.Methods Twenty depressive patients with diurnal rhythm,20 depressive patients without diurnal rhythm and 20 gender-,age-,education-matched healthy controls were scanned with 3.0 T MRI Scanner.According to Results of ANOVA,group-wise two sample t-test was completed.The correlation analysis were conducted between ALFF of significant difference brain regions and the score of Hamilton rating scale for depression.Results The brain regions showing significant differences among three groups were located in the right parahippocampal gyrus(MNI:18,-36,-9;K=136),left parietal lobe(MNI:-54,-45,42;K=86),left cerebellum crus(MNI:-84,-60,36;K=86) and right cerebellum crus(MNI:9,-78,-36;K=91)(P<0.05,Alphasim correct).Compared with non-diurnal rhythm group,the diurnal rhythm group showed significantly increased ALFF in the right parahippocampal gyrus.Compared with healthy group,the diurnal rhythm group showed significantly increased ALFF in right parahippocampal gyrus,left parietal lobe,and significantly decreased ALFF in left cerebellum crus 1 and right cerebellum crus 2.Compared with healthy group,the non-diurnal rhythm group showed significantly increased ALFF in left parietal lobe,and significantly decreased ALFF in left cerebellum crus 1 and bilateral cerebellum crus 2.No correlation between ALFF of significant difference brain regions and clinical symptoms was found(P>0.05).Conclusion The diurnal rhythm observed in depression may be associated with aberrant activity of parahippocampal gyrus.

Depression is a common mental disorder with high incidence rate and low remission rate.The prediction of therapeutic effect in depression is limited to clinical features and neuroimaging.Reviewed the Results of magnetic resonance imaging for predicting the treatment response in depression and explored the Objective image markers for predicting the therapeutic effect in depression.It showed that the studies mainly focused on emotion regulation neural circuitry and few on reward neural circuitry.Prefrontal cortex,cingulate cortex,amygdala and hippocampus play important roles on predicting therapeutic effect.The study of magnetic resonance imaging for predicting therapeutic effect in depression is a feasible research field.More researches of finding the role of reward neural circuits in predicting the effect of antidepressants are needed.The brain structure and function of the neural circuits involved in depression and predicting the effect of anti-depression need to be studied by multimodal MRI method.

Objective To investigate the changes of cortical thickness and surface area in patients with bipolar depression(BD),and to explore the relationship between abnormal changes in gray matter and clinical symptoms.Methods 28 BD patients and 28 healthy controls underwent T1-weighted MRI.The Freesurfer software was used to process the T1 images,which used a set of automated sequences to analyze cortical thickness and surface area on 66 regions (33 regions of each hemisphere),and the correlation with clinical features was also calculated.Results Compared with controls,BD patients showed thinner cortical thickness in left medial orbitofrontal cortex((2.40±0.12) mm vs (2.55 ±0.18) mm,P=1.2× 10-3) and left rostral anterior cingulate((2.66±0.21) mm vs (2.88±0.27) mm,P=3.1 × 10-4),and smaller area of left cuneus((1 443.13± 131.00) mm2vs (6 634.70±600.16) mm2,P=2.7× 10-4) and right superior frontal gyrus ((6 634.70±600.16) mm2vs (7 300.50±653.39) mm2,P=1.3× 10-3).In addition,the negatively correlation was found between the cortical area of left cuneus and effective illness duration (r=-0.471,P=0.018),and the cortical thickness in left rostral anterior cingulate and total score of HAMD-17(17-item Hamilton Rating Scale for Depression) (r=-0.508,P=0.009).Conclusion There are abnormal altertion of cortical thickness and cortical areas of emotional circuit in bipolar depression,but the brain areas are not completely overlapping.Correlation analysis suggests that cortical thickness and area is related to different clinical features.