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Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.
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OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.
Subject(s)
Carcinoma, Hepatocellular , Hepatectomy , Hypertension, Portal , Liver Neoplasms , Nomograms , Humans , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Hepatectomy/methods , Hepatectomy/adverse effects , Male , Female , Middle Aged , Hypertension, Portal/surgery , Hypertension, Portal/etiology , Aged , Risk Factors , Postoperative Complications/etiology , Liver Failure/etiology , Liver Failure/surgery , Retrospective Studies , AdultABSTRACT
Radiotherapy resistance is a major cause of treatment failure and leads to poor prognosis in nasopharyngeal carcinoma (NPC). Evidences indicate that microRNA (miRNAs) are closely associated with radiotherapy for NPC. In this study, we found that the expression level of miR-92b-3p was significantly higher in radiotherapy-sensitive NPC patients than in radiotherapy-resistant patients. High expression of miR-92b-3p was associated with good prognosis in patients with NPC, and high expression of FHL2 was associated with poor prognosis in patients with NPC. It was predicted that miR-92b-3p could directly target and bind FHL2. Overexpression of miR-92b-3p significantly inhibited FHL2 expression at the mRNA as well as protein levels, while inhibition of miR-92b-3p expression significantly upregulated FHL2 expression. Overexpression of miR-92b-3p significantly reduced proliferation and colony formation in NPC cells. Inhibition of miR-92b-3p attenuated the sensitivity of nasopharyngeal carcinoma to radiotherapy, while simultaneous inhibition of miR-92b-3p and FHL2 increased the sensitivity of NPC to radiotherapy. Our findings highlighted that miR-92b-3p is closely associated with radiotherapy sensitivity and prognosis in NPC patients and may improve the sensitivity of NPC to radiotherapy by targeting FHL2.
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Plant biology studies in the post-genome era have been focused on annotating genome sequences' functions. The established plant mutant collections have greatly accelerated functional genomics research in the past few decades. However, most plant genome sequences' roles and the underlying regulatory networks remain substantially unknown. Clustered, regularly interspaced short palindromic repeat (CRISPR)-associated systems are robust, versatile tools for manipulating plant genomes with various targeted DNA perturbations, providing an excellent opportunity for high-throughput interrogation of DNA elements' roles. This study compares methods frequently used for plant functional genomics and then discusses different DNA multi-targeted strategies to overcome gene redundancy using the CRISPR-Cas9 system. Next, this work summarizes recent reports using CRISPR libraries for high-throughput gene knockout and function discoveries in plants. Finally, this work envisions the future perspective of optimizing and leveraging CRISPR library screening in plant genomes' other uncharacterized DNA sequences.
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Background: Systemic inflammatory response is a hallmark of cancer and plays a significant role in the development and progression of various malignant tumors. This research aimed to estimate the prognostic function of the C-reactive protein-albumin ratio (CAR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and compare it with other inflammation-based prognostic scores, including the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, systemic immune inflammation index, prognostic index, Glasgow prognostic score, and modified Glasgow prognostic score. Methods: Retrospective analysis was conducted on data from 1039 HCC cases who underwent curative liver resection. The prognostic performance of CAR was compared with other scores using the area under the time-dependent receiver operating characteristic (t-ROC) curve. Multivariable Cox regression analyses were performed to confirm independent predictors for disease-free survival (DFS) and overall survival (OS). Results: The area under the t-ROC curve for CAR in the evaluation of DFS and OS was significantly greater than that of other scores and alpha-fetoprotein (AFP). Patients were stratified based on the optimal cut-off value of CAR, and the data revealed that both DFS and OS were remarkably worse in the high-CAR set compared to the low-CAR set. Multivariable Cox analysis demonstrated that CAR was an independent prognostic parameters for assessing DFS and OS. Regardless of AFP levels, all patients were subsequently divided into significantly different subgroups of DFS and OS based on CAR risk stratification. Similar results were observed when applying CAR risk stratification to other scoring systems. CAR also showed good clinical applicability in patients with different clinical features. Conclusion: CAR is a more effective inflammation-based prognostic marker than other scores and AFP in predicting DFS as well as OS among patients with HCC after curative hepatectomy.
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With rapid industrialization and urbanization in China, inadequate preservation of traditional architecture coupled with natural deterioration have led to the fragmentation of architectural landscapes. Drawing from ecological fragmentation research in landscape ecology, we consider the cultural landscape as our research object, viewing buildings as landscape patches, and determine a system for measuring architectural landscape fragmentation in traditional villages. The study shows the degree of landscape fragmentation can reveal the characteristics of traditional villages and the process of regional modernization. The results are as follows: (1) From the perspective of landscape diversity, the study area was rich in landscape types in all dimensions, and the relative evenness index was high, signifying evident or severe fragmentation. (2) The index of landscape heterogeneity in the dimensions of building quality, height, and landscape appearance is low in the study area, with mild levels of landscape fragmentation caused by heterogeneity in the aforementioned dimensions. (3) Mild fragmentation suggests the integrity and homogeneity of architectural landscape types, reflecting a lagging level of economic development, whereas high fragmentation signifies rapid economic development, leading to a substantial deterioration in the integrity and homogeneity of architectural landscape types. Therefore, efforts to preserve and develop traditional villages should not solely aim for low fragmentation as it could potentially constrain sustainable development.
Subject(s)
Conservation of Natural Resources , Ecology , Conservation of Natural Resources/methods , China , Urbanization , Sustainable Development , EcosystemABSTRACT
Hepatocellular carcinoma (HCC), a highly malignant digestive system tumor, poses substantial challenges due to its intricate underlying causes and pronounced post-surgery recurrence. Consequently, the prognosis for HCC remains notably unfavorable. The endorsement of sorafenib and PD-L1 inhibitors for HCC signifies the onset of a new era embracing immunotherapy and targeted treatment approaches for this condition. Hence, comprehending the mechanisms underpinning targeted immune combination therapy has become exceedingly vital for the prospective management of HCC patients. This article initially presents a triumphant instance of curative treatment involving the combination of TKI and PD-1 inhibitor subsequent to liver resection, targeting an advanced stage HCC as classified by the BCLC staging system. The case patient carries a decade-long history of hepatitis B, having undergone a regimen of 20 courses of treatments involving apatinib and camrelizumab. Throughout the treatment period, no occurrences of grade 3 or 4 adverse events (AE) were noted. Subsequently, the patient underwent a left hepatectomy. Following the hepatectomy, their serum AFP levels have consistently remained within normal limits, and CT imaging has indicated the absence of tumor recurrence over a span of 36 months. The patient had been reviewed on time for two years after the operation. The last time a CT was performed for this patient in our hospital was 7 May 2021, and no new tumors were found. Follow-up is still ongoing. When applying combined targeted immune transformation therapy using TKI and ICI for a patient with BCLC advanced stage HCC, apatinib treatment serves a dual purpose. It inhibits the survival and angiogenesis of tumor cells, while also enhancing the efficacy of camrelizumab in obstructing the interaction between PD-1 and PD-L1. This restoration of T cell cytotoxicity subsequently facilitates the elimination of tumor cells, leading to an enhanced anticancer effect.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/surgery , Hepatectomy , Prospective Studies , Liver Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapyABSTRACT
Objective: The purpose of this study is to investigate the shared and distinct thalamic-cortical circuit between bipolar depression and remission, as well as to investigate the trait and state-related characteristics of the abnormal thalamic-cortical circuit in bipolar disorder. Methods: Resting-state functional magnetic resonance imaging was performed on 38 bipolar depression patients, 40 bipolar remission patients, and 39 gender-matched healthy controls (rsfMRI). The thalamic subregions were used as seed points to draw the functional connectivity of the entire brain, and then the shared and distinct thalamic-cortical circuits between bipolar depression and remission were compared. Results: When compared to the healthy group, both groups of patients had significantly lower functional connectivity between the rostral temporal thalamus and the lingual gyrus, the posterior parietal thalamus, the precuneus/cerebellum, and the occipital thalamus and the precuneus; however, functional connectivity between the premotor thalamus and the superior medial frontal was significantly lower in depression. Conclusion: This study discovered that both bipolar depression and remission had abnormal sensorimotor-thalamic functional connectivity, implying that it is a trait-related characteristic of bipolar disorder; however, the decline in prefrontal-thalamic connectivity exists specifically in bipolar depression, implying that it is a state-related characteristic of bipolar disorder.
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This study aims to fabricate immobilized lipases for efficient preparation of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) through acidolysis of glycerol tripalmitate (PPP). Twelve (three types) supports and five lipases were studied carefully. Among them, the immobilized Thermomyces lanuginosa lipase (TLL) samples exhibited overall better performance than that of other immobilized lipases. Particularly, organic groups functionalized SBA-15 (R-SBA-15) supported TLL (TLL@R-SBA-15) samples gave PPP conversion from 97.70 to 99.00 % and OPO content from 59.52 to 64.73 %. After optimization, PPP conversion up to 99.07 %, OPO content 73.15 % and sn-2 palmitic acid content 90.09 % were obtained with TLL@C18H37-SBA-15 as catalyst. Moreover, TLL@C18H37-SBA-15 exhibited better acidolysis performance from 50 °C than that from 60 to 80 °C, which helped inhibit acyl migration. In addition, after 5 cycles of reuse, TLL@C18H37-SBA-15 retained 81.04 % (based on OPO content) and 98.88 % (based on sn-2 palmitic acid content) of its initial activity, indicating it had an attractive prospect in future applications.
Subject(s)
Eurotiales , Palmitic Acid , Silicon Dioxide , Lipase , Enzymes, ImmobilizedABSTRACT
OBJECTIVES: Up to 70%-80% of patients with bipolar disorder are misdiagnosed as having major depressive disorder (MDD), leading to both delayed intervention and worsening disability. Differences in the cognitive neurophysiology may serve to distinguish between the depressive phase of type 1 bipolar disorder (BDD-I) from MDD, though this remains to be demonstrated. To this end, we investigate the discriminatory signal in the topological organization of the functional connectome during a working memory (WM) task in BDD-I and MDD, as a candidate identification approach. METHODS: We calculated and compared the degree centrality (DC) at the whole-brain voxel-wise level in 31 patients with BDD-I, 35 patients with MDD, and 80 healthy controls (HCs) during an n-back task. We further extracted the distinct DC patterns in the two patient groups under different WM loads and used machine learning approaches to determine the distinguishing ability of the DC map. RESULTS: Patients with BDD-I had lower accuracy and longer reaction time (RT) than HCs at high WM loads. BDD-I is characterized by decreased DC in the default mode network (DMN) and the sensorimotor network (SMN) when facing high WM load. In contrast, MDD is characterized by increased DC in the DMN during high WM load. Higher WM load resulted in better classification performance, with the distinct aberrant DC maps under 2-back load discriminating the two disorders with 90.91% accuracy. CONCLUSIONS: The distributed brain connectivity during high WM load provides novel insights into the neurophysiological mechanisms underlying cognitive impairment of depression. This could potentially distinguish BDD-I from MDD if replicated in future large-scale evaluations of first-episode depression with longitudinal confirmation of diagnostic transition.
Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Humans , Bipolar Disorder/diagnosis , Magnetic Resonance Imaging/methods , Depressive Disorder, Major/diagnosis , Memory, Short-Term/physiology , Depression , Brain/diagnostic imagingABSTRACT
Background: The evidence of some previous papers was insufficient in studying the causal association between interpregnancy interval (IPI) and adverse pregnancy outcomes. In addition, more literature have been updated worldwide during the last 10 years. Methods: English and Chinese articles published from January 1980 to August 2021 in the databases of PubMed, Cochrane Library, Ovid, Embase, China Biology Medicine disc (CBM), and China National Knowledge Infrastructure (CNKI) were searched. Then following the inclusion and exclusion criteria, we screened the articles. Utilizing the Newcastle-Ottawa Scale (NOS), we evaluated the quality of the included articles. The literature information extraction table was set up in Excel, and the meta-analysis was performed with Stata 16.0 software (Texas, USA). Results: A total of 41 articles were included in the meta-analysis, and NOS scores were four to eight. The short IPI after delivery was the risk factor of preterm birth (pooled odds ratio 1.49, 95% confidence interval 1.42-1.57), very preterm birth (pooled OR: 1.82, 95% CI: 1.55-2.14), low birth weight (pooled OR: 1.33, 95% CI: 1.24-1.43), and small for gestational age (pooled OR: 1.14, 95% CI: 1.07-1.21), offspring death (pooled OR: 1.60, 95% CI: 1.51-1.69), NICU (pooled OR: 1.26, 95% CI: 1.01-1.57), and congenital abnormality (pooled OR: 1.10, 95% CI: 1.05-1.16), while was not the risk factor of gestational hypertension (pooled OR: 0.95, 95% CI: 0.93-0.98) or gestational diabetes (pooled OR: 1.06, 95% CI: 0.93-1.20). Conclusion: Short IPI (IPI < 6 months) can lead to adverse perinatal outcomes, while it is not a risk factor for gestational diabetes and gestational hypertension. Therefore, more high-quality studies covering more comprehensive indicators of maternal and perinatal pregnancy outcomes are needed to ameliorate the pregnancy policy for women of childbearing age.
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OBJECTIVE: To evaluate the clinical application and surgical efficacy of the chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap for the reconstruction of the large area of deep wound in foot and ankle. METHODS: Clinical data of 32 cases who underwent chimeric anterolateral thigh perforator flap to repair the large area of deep wound of the foot and ankle from January 2015 to December 2018 were retrospectively analyzed. The sizes of the defects ranged from 18 cm × 10 cm to 35 cm × 20 cm, with exposed tendon and bone and/or partial defects and necrosis, contaminations, accompanied by different degrees of infection. Following the radical debridement and VSD, chimeric anterolateral thigh perforator flap was employed to repair the deep wounds according to the position, site and deep-tissue injury of the soft-tissue defects. The skin flap and muscle flap were fanned out on the wound, and single- or two-staged split-thickness skin grafting was performed on the muscle flap. The operation time and blood loss were recorded. The survival and healing conditions of the operational site with chimeric anterolateral thigh perforator flap were evaluated post-operationally. Complications at both recipient site and donor site were carefully recorded. RESULTS: The mean time of the operation was 325.5 min and average blood loss was 424.8 mL. Among the 32 cases, two cases developed vascular crisis, which were alleviated with intensive investigation and treatment; Four cases suffered from partial necrosis of the flap or skin graft on the muscle flap or on the residual local wound, which were improved after treatment of further dressing change and skin grafting. Another four cases experienced post-traumatic osteomyelitis accompanied by bone defect were treated with simple bone grafting or Mesquelet bone grafting at 6-8 months after wound healing. Postoperatively, the wounds were properly healed, and the infection was effectively controlled without sinus tract forming. Overall, all 32 cases received satisfactory efficacy, without influencing subsequent functional reconstruction, and observed infection during the 12-36 months post-operational follow-up. CONCLUSION: The chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap provides an effective and relative safe procedure for the repair of a large area of deep wound in the foot and ankle, particularly with irregular defect or deep dead space.
Subject(s)
Ankle Injuries/surgery , Femoral Artery/transplantation , Perforator Flap/transplantation , Plastic Surgery Procedures/methods , Soft Tissue Injuries/surgery , Thigh/blood supply , Wound Healing , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Introduction: Previous studies have primarily focused on the neuropathological mechanisms of the emotional circuit present in bipolar mania and bipolar depression. Recent studies applying resting-state functional magnetic resonance imaging (fMRI) have raise the possibility of examining brain-wide networks abnormality between the two oppositional emotion states, thus this study aimed to characterize the different functional architecture represented in mania and depression by employing group-independent component analysis (gICA). Materials and Methods: Forty-one bipolar depressive patients, 20 bipolar manic patients, and 40 healthy controls (HCs) were recruited and received resting-state fMRI scans. Group-independent component analysis was applied to the brain network functional connectivity analysis. Then, we calculated the correlation between the value of between-group differences and clinical variables. Results: Group-independent component analysis identified 15 components in all subjects, and ANOVA showed that functional connectivity (FC) differed significantly in the default mode network, central executive network, and frontoparietal network across the three groups. Further post-hoc t-tests showed a gradient descent of activity-depression > HC > mania-in all three networks, with the differences between depression and HCs, as well as between depression and mania, surviving after family wise error (FWE) correction. Moreover, central executive network and frontoparietal network activities were positively correlated with Hamilton depression rating scale (HAMD) scores and negatively correlated with Young manic rating scale (YMRS) scores. Conclusions: Three brain networks heighten activity in depression, but not mania; and the discrepancy regions mainly located in prefrontal, which may imply that the differences in cognition and emotion between the two states is associated with top-down regulation in task-independent networks.
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BACKGROUND: Previous studies suggested bipolar disorder caused an aberrant alteration in the insular, putamen, and left superior frontal gyrus, which are the main components of the hate circuit. However, the relationship between the hate circuit and the pathophysiologic substrate underlying different phases of bipolar disorder remain unclear. In this study, we aimed to identify group differences of resting-state functional connectivity within the hate circuit in healthy controls (HCs) and bipolar patients in different mood states. METHODS: Resting-state functional magnetic resonance imaging of the brain were acquired from 54 HCs and 81 patients with bipolar disorder including 20 with bipolar mania (BM), 35 with bipolar depression (BD), and 26 with bipolar euthymia (BE). We selected bilateral insula (L.INS and R.INS), bilateral putamen (L.PUT and R.PUT), and left superior frontal gyrus (L.SFGd) as seed regions, and conducted the seed-based functional connectivity analysis to identify group differences of connectivity strength within the hate circuit. Spearman correlations were performed to evaluate the relationship between the hate circuit and manic/depressive symptoms. RESULTS: Significant group differences of connectivity strength within the hate circuit were found in links of the R.INS-L.SFGd, R.PUT-L.SFGd, and L.INS- R.PUT after false discovery rate was corrected. The BM group showed an opposite hate circuit pattern to BD, BE, and HCs. The BD group showed decreased hate circuit connectivity in the L.INS-R.PUT compared with the BE group. No significant difference was detected among BD, BE, and HCs. Furthermore, functional connectivity of the R.INS-L.SFGd and R.PUT-L.SFGd were positively correlated with manic symptoms, while the L.INS- R.PUT was negatively correlated with depressive symptoms. CONCLUSIONS: Our preliminary findings suggest that altered functional connectivity of the hate circuit in different mood phases may be related to state markers and underpin the neuropathological basis of bipolar disorder.
Subject(s)
Ankle , Joint Instability , Ankle Joint , China , Humans , Joint Instability/diagnosis , Surveys and Questionnaires , TranslationsABSTRACT
BACKGROUND: Working memory (WM) deficit is a feature persistently reported across mania, depression, and euthymic periods of bipolar disorder (BD). WM capacity relates to distributed brain regions that are systemically organized at the connectome level. It is not clear whether the same disruption of this network-level organization underlies the WM impairment seen in different phases of BD. METHODS: We used graph theory to examine the topology of the functional connectome in different granularity in 143 subjects (72 with BD [32 depression; 15 mania; 25 euthymic] and 71 healthy controls) during a n-back task. Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients. RESULTS: Altered topological properties characterised by an increase in small-worldness of the whole-brain connectome, were specific for bipolar depressed, but not in manic and euthymic states. Depressed subjects showed a shift in the distribution of the number of connections per brain region (degree) within the connectome during WM task. Increased small-worldness related to worse WM accuracy in patients with more severe depression, anxiety and illness burden. LIMITATIONS: We used only 2-back load, limiting our ability to study the parametric effects of task demand. CONCLUSIONS: We demonstrate a putative state-dependent mechanistic link between connectome topology, hub re-distribution and impaired n-back performance in bipolar disorder. The aberrant task-dependent modulation of the connectome relates to worse WM performance especially when anxiety and depression are prominent in BD.
Subject(s)
Bipolar Disorder , Connectome , Bipolar Disorder/complications , Depression , Humans , Magnetic Resonance Imaging , Mania , Memory Disorders , Memory, Short-TermABSTRACT
BACKGROUND: Bipolar depression (BDD) and major depressive disorder (MDD) are two diseases both characterized by depressed mood and diminished interest or pleasure. Recent neuroimaging studies have implicated the thalamo-cortical circuit in mood disorders, and the present study aimed to map thalamo-cortical connectivity to explore the dissociable and common abnormalities between bipolar and major depression in this circuit. METHOD: Applying resting-state functional magnetic resonance imaging (fMRI), we mapped the thalamo-cortical circuit using a fine-grained thalamic atlas with 8 sub-regions bilaterally in 38 BDD patients, 42 MDD patients and 39 healthy controls (HCs). Correlation analysis was then performed between thalamo-cortical connectivity and clinical variables. RESULT: The findings showed that both patient groups exhibited prefronto-thalamo-cerebellar and sensorimotor-thalamic hypoconnectivity, while the abnormalities in MDD were more extensive. Particularly, MDD group showed decreased thalamic connectivity with the salience network including the insula, anterior cingulate cortex (ACC), and striatum. No correlations were found between the abnormal thalamo-cortical connectivity and clinical symptoms in either patient group. LIMITATION: Most patients in our study were taking drugs at the time of scanning, which may confound our findings. CONCLUSION: Our finding suggest that the thalamo-cortical hypofunction is a common neuro-substrate for BDD and MDD. Specifically, the hypoconnectivity between the thalamus and salience network including the insula, ACC and striatum may be a distinguished biomarker for MDD, which may help to differentiate these two emotional disorders.
Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Bipolar Disorder/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Depressive Disorder, Major/diagnostic imaging , Humans , Magnetic Resonance Imaging , Thalamus/diagnostic imagingABSTRACT
BACKGROUND: Surgical treatment of both-column acetabular fractures is challenging because of the complex acetabular fracture patterns and the curved surface of the acetabulum. Seldom study has compared the application of three-dimensional (3D) printing technology and traditional methods of contouring plates intra-operatively for the surgical treatment of both-column acetabular fractures. We presented the use of both 3D printing technology and a virtual simulation in pre-operative planning for both-column acetabular fractures. We hypothesized that 3D printing technology will assist orthopedic surgeons in shortening the surgical time and improving the clinical outcomes. METHODS: Forty patients with both-column acetabular fractures were recruited in the randomized prospective case-control study from September 2013 to September 2017 for this prospective study (No. ChiCTR1900028230). We allocated the patients to two groups using block randomization (3D printing group, nâ=â20; conventional method group, nâ=â20). For the 3D printing group, 1:1 scaled pelvic models were created using 3D printing, and the plates were pre-contoured according to the pelvic models. The plates for the conventional method group were contoured during the operation without 3D printed pelvic models. The operation time, instrumentation time, time of intra-operative fluoroscopy, blood loss, number of times the approach was performed, blood transfusion, post-operative fracture reduction quality, hip joint function, and complications were recorded and compared between the two groups. RESULTS: The operation and instrumentation times in the 3D printing group were significantly shorter (130.8â±â29.2âmin, tâ=â-7.5, Pâ<â0.001 and 32.1â±â9.5âmin, tâ=â-6.5, Pâ<â0.001, respectively) than those in the conventional method group. The amount of blood loss and blood transfusion in the 3D printing group were significantly lower (500 [400, 800] mL, Mann-Whitney Uâ=â74.5, Pâ<â0.001 and 0 [0,400] mL, Mann-Whitney Uâ=â59.5, Pâ<â0.001, respectively) than those in the conventional method group. The number of the approach performed in the 3D printing group was significantly smaller than that in the conventional method group (pararectus + Kocher-Langenbeck [K-L] approach rate: 35% vs. 85%; χâ=â10.4, Pâ<â0.05). The time of intra-operative fluoroscopy in the 3D printing group was significantly shorter than that in the conventional method group (4.2â±â1.8 vs. 7.7â±â2.6âs; tâ=â-5.0, Pâ<â0.001). The post-operative fracture reduction quality in the 3D printing group was significantly better than that in the conventional method group (good reduction rate: 80% vs. 30%; χâ=â10.1, Pâ<â0.05). The hip joint function (based on the Harris score 1 year after the operation) in the 3D printing group was significantly better than that in the conventional method group (excellent/good rate: 75% vs. 30%; χâ=â8.1, Pâ<â0.05). The complication was similar in both groups (5.0% vs. 25%; χâ=â3.1, Pâ=â0.182). CONCLUSIONS: The use of a pre-operative virtual simulation and 3D printing technology is a more effective method for treating both-column acetabular fractures. This method can shorten the operation and instrumentation times, reduce blood loss, blood transfusion and the time of intra-operative fluoroscopy, and improve the post-operative fracture reduction quality. CLINICAL TRAIL REGISTRATION: No.ChiCTR1900028230; http://www.chictr.org.cn.
Subject(s)
Acetabulum/injuries , Computer Simulation , Fractures, Bone/surgery , Printing, Three-Dimensional , Adult , Blood Transfusion , Female , Humans , Male , Middle Aged , Postoperative Complications/therapy , Prospective StudiesABSTRACT
Concerns over the health risk of the widely distributed, commonly used titanium dioxide nanoparticles (nano-TiO2 ) are increasing worldwide. Yet, up-to-now, our understanding in their potential effects on the cardiovascular system is very limited and the toxicological mechanisms are still unclear. In the present study, the CCK-8 assay was performed to determine the cytotoxicity of four sizes (10, 30, 50, and 100 nm) of anatase nano-TiO2 on human umbilical vein endothelial cells (HUVECs) in culture, and the flow cytometry was employed to investigate the potential of these nano-TiO2 to induce the apoptosis of HUVECs. The apoptotic pathway was also probed through the determination of the protein expression and activation of p53, Bax, Bcl-2, caspases-9, -7, -3, and PARP by western blot. The results showed that at the administrative levels (1, 5, 25 µg/mL), all the four sizes of nano-TiO2 could significantly inhibit the viability of HUVECs and elicit significant apoptosis in them, compared with the negative control (P < .05, P < .01). Moreover, the apoptotic rates of HUVECs were increased respectively with the elevating levels and decreasing sizes of the administrative nano-TiO2 , showing a clear dose- and size-dependent effect relationships. Interestingly, the increasing phosphorylation of p53, decreasing ratio of Bcl-2/Bax, and enhancing activation of the downstream proteins caspase-9, -7, -3, and PARP, were also observed with the decreasing sizes of the administrative nano-TiO2 in the western blot, indicating that the intracellular approach of apoptosis, the p53-caspase pathway, is the major way of the nano-TiO2 -mediated apoptosis in HUVECs in culture and that the size is an important parameter that may determine the potential of nano-TiO2 to induce cellular response. In conclusion, these results suggested that high levels of nano-TiO2 exposure may pose potential risks to human cardiovascular health by inducing cardiovascular EC apoptosis.
Subject(s)
Apoptosis/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Nanoparticles/toxicity , Titanium/toxicity , Caspase 9/metabolism , Caspases/metabolism , Cells, Cultured , Cytoplasm/metabolism , Human Umbilical Vein Endothelial Cells/physiology , Humans , Particle Size , Phosphorylation , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction/drug effects , Titanium/chemistryABSTRACT
With the growing production and applications of silica nanoparticles (SiNPs), human exposure to these nanoparticles continues to increase. However, the possible hazards that SiNP exposure may pose to human cardiovascular system and the underlying mechanisms remain unclear. In the present study, the flow cytometry was employed to investigate the potential of four sizes (10, 25, 50, 100 nm) of SiNPs to induce the apoptosis of human umbilical vein endothelial cells (HUVECs) in culture. The apoptotic pathway was also explored through the determination of the protein expression and/or activation of p53, Bcl-2, Bax, caspases-9, -7, -3, and PARP by western blot. The results showed that all the four sizes of SiNPs could significantly elicit apoptosis in HUVECs at the tested concentrations (1, 5, 25 µg/mL), compared with the negative control (p < 0.05, p < 0.01). Moreover, the apoptotic rates were increased with the elevating levels and decreasing sizes of administrative SiNPs, showing both dose- and size-dependent effect relationships. Interestingly, the enhancing phosphorylation of p53 protein (Ser15), decreasing ratio of Bcl-2/Bax protein, and elevating activation of the downstream proteins, caspase-9, -7, -3 and PARP, were also observed with the decreasing sizes of tested SiNPs, indicating that the p53-caspase pathway is the main way of the SiNP-mediated apoptosis in HUVECs and that the size is an important parameter that determines the SiNPs' potential to induce cellular response.