[Clinical Characteristics Analysis of 1051 Cases of Cleft Lip With/Without Cleft Palate in the Ethnic Tibetan Population]. / 1051ä¾‹è—æ—å”‡è ­è£‚æ‚£è€ ä¸´åºŠç‰¹å¾åˆ†æž.

Objective: To examine the characteristics of the prevalence of congenital cleft lip with/without cleft palate in the ethnic Tibetan population and to provide support for the precise prevention and treatment of cleft lip with/without cleft palate in the Tibetan population. Methods: The clinical data of Tibetan patients with cleft lip with/without cleft palate were collected and the clinical characteristics of the patients were analyzed. The patients' age ranged from 2 months to 51 years old. All the subjects were admitted to West China Stomatology Hospital, Sichuan University for the treatment of cleft lip with/without cleft palate between January 2016 and August 2023. Most of the subjects came from Sichuan Province and the Tibet Autonomous Region. Results: A total of 1051 patients were enrolled and children aged under 12 months (460 cases) accounted for the largest proportion. Among the subjects, 383 had cleft lip only (36.44%), 140 had cleft palate only (13.32%), and 528 had cleft lip with cleft palate (50.24%). The male-to-female ratios of patients with cleft lip only (0.99∶1), cleft palate only (0.54∶1), and cleft lip with cleft palate (1.67∶1) exhibited significant differences (P<0.001). However, there was no significant difference in the male-to-female ratio in patients with cleft lip only or those with cleft lip with cleft palate when the subjects were divided into two groups according to whether they had unilateral or bilateral cleft lip with/without cleft palate. Most of the patients with bilateral cleft lip were female, while most of the patients with unilateral cleft lip and unilateral or bilateral cleft lip with cleft palate were male. The unilateral cleft lip with/without cleft palate was located predominantly on the left side. Syndromic cleft lip with/without cleft palate accounted for 3.43% of all the cases and the most common concomitant deformity was congenital heart disease. 3.81% (40 cases) of the patients had a family history. In the patients with cleft lip only and those with cleft palate only, the proportion of patients having parents with corresponding phenotypes was higher than those of other phenotypes of cleft lip with/without cleft palate. Regarding the birth time distribution of the children with cleft lip with/without cleft palate, Spring saw the highest number of births of these children (311 cases, 29.59%), while Winter saw the lowest number of births (231 cases, 21.98%). Conclusion: The cases of cleft lip with/without cleft palate in the ethnic Tibetan population are predominantly cleft lip and palate. Unilateral cleft lip only or cleft lip with palate is predominantly located on the left side. Lip disease phenotypes may be more heritable.

Association between variants around IRF6 and non-syndromic orofacial cleft in Western Han Chinese.

OBJECTIVES: Considering limitations of previous studies and differences across populations and subtypes, this study aimed to identify new potential SNPs around IRF6 associated with non-syndromic orofacial cleft (NSOC) in Western Han Chinese. MATERIALS AND METHODS: We recruited 376 NSOC case-parent trios, including 125 non-syndromic cleft lip only (NSCLO) trios, 151 non-syndromic cleft lip and palate (NSCLP) trios, and 100 non-syndromic cleft palate only (NSCPO) trios. Twenty-two single-nucleotide polymorphisms (SNPs) were genotyped using MassARRAY method. Hardy-Weinberg equilibrium test, allelic transmission disequilibrium test (TDT) analysis, sliding-window haplotype TDT analysis, and tests for parent-of-origin effect were performed using the PLINK software. Pairwise linkage disequilibrium (LD) was computed using the Haploview program. RESULTS: In TDT analysis, allele A at rs17015217 (p = 0.00011, OR = 0.61 and 95% CI: 0.47-0.78) and allele T at rs12080691 (p = 0.00011, OR = 0.61 and 95% CI: 0.47-0.78) were under-transmitted among NSCLO trios but over-transmitted among NSCPO trios. Haplotypes showing evidence of under-transmission in NSCLO trios were over-transmitted in NSCPO trios. In tests for parent-of-origin effects, T allele at rs12080691 presented paternal under-transmission among NSCLO trios but over-transmission among NSCPO trios. CONCLUSIONS: Allele A at rs17015217 and allele T at rs12080691 are associated with NSCLO and NSCPO with potential to have opposite effects on two subtypes in this sample from Western Han Chinese.

Differentiating thymoma, thymic carcinoma and lymphoma based on collagen fibre patterns with T2- and diffusion-weighted magnetic resonance imaging.

OBJECTIVES: The amount and distribution of intratumoural collagen fibre vary among different thymic tumours, which can be clearly detected with T2- and diffusion-weighted MR images. To explore the incidences of collagen fibre patterns (CFPs) among thymomas, thymic carcinomas and lymphomas on imaging, and to evaluate the efficacy and reproducibility of CFPs in differential diagnosis of thymic tumours. MATERIALS AND METHODS: Three hundred and ninety-eight patients with pathologically diagnosed thymoma, thymic carcinoma and lymphoma who underwent T2- and diffusion-weighted MR imaging were retrospectively enrolled. CFPs were classified into four categories: septum sign, patchy pattern, mixed pattern and no septum sign. The incidences of CFPs were compared among different thymic tumours, and the efficacy and reproducibility in differentiating the defined tumour types were analysed. RESULTS: There were significant differences in CFPs among thymomas, thymic squamous cell carcinomas (TSCCs), other thymic carcinomas and neuroendocrine tumours (OTC&NTs) and thymic lymphomas. Septum signs were found in 209 (86%) thymomas, which differed between thymomas and any other thymic neoplasms (all p < 0.005). The patchy, mixed patterns and no septum sign were mainly seen in TSCCs (80.3%), OTC&NTs (78.9%) and thymic lymphomas (56.9%), respectively. The consistency of different CFP evaluation between two readers was either good or excellent. CFPs achieved high efficacy in identifying the thymic tumours. CONCLUSION: The CFPs based on T2- and diffusion-weighted MR imaging were of great value in the differential diagnosis of thymic tumours. KEY POINTS: • Significant differences are found in intratumoural collagen fibre patterns among thymomas, thymic squamous cell carcinomas, other thymic carcinomas and neuroendocrine tumours and thymic lymphomas. • The septum sign, patchy pattern, mixed pattern and no septum sign are mainly seen in thymomas (86%), thymic squamous cell carcinomas (80.3%), other thymic carcinomas and neuroendocrine tumours (79%) and thymic lymphomas (57%), respectively. • The collagen fibre patterns have high efficacy and reproducibility in differentiating thymomas, thymic squamous cell carcinomas and thymic lymphomas.

Alterations in functional connectivity and interactions in resting-state networks in female patients with functional constipation.

BACKGROUND : Patients with functional constipation (FCon) have been reported with brain functional and structural abnormalities. However, no studies have been performed to investigate the differences in resting-state networks (RSNs) and changes in functional connectivity (FC) between RSNs in patients with FCon. Thus, the current study aimed to identify abnormal FC within and interaction between RSNs in patients with FCon to reveal the underlying neural mechanism. METHODS: Functional MRI with independent component analysis was applied to investigate alterations in FC within and functional network connectivity (FNC) between RSNs including default mode- (DMN), basal ganglia- (BGN), salience- (SN), and left and right control executive-networks (LCEN/RCEN) in 39 female patients with FCon and 36 female healthy controls (HC). Patient Assessment of Constipation Quality of Life Scale (PAC-QOL) and Patient Assessment of Constipation Symptom Scale (PAC-SYM) were used to assess the constipation symptoms. RESULTS: FCon patients had changed regional FC between different networks contributing to the abnormal FNC among RSNs compared with HC. Patients with greater stool syndromes had increased FNC of BGN-SN and DMN-LCEN, and patients with greater worries/concerns and PAC-QOL total score had reduced FNC of SN-RCEN. The greater strength changes in FC in prefrontal and parietal cortices were associated with higher negative emotion scores and greater rectal symptoms, respectively. CONCLUSION: The findings suggested that FCon patients had altered FC within and interactions between RSNs and the brain FC changes were associated with constipation symptoms and altered emotions.

Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft.

Nonsyndromic orofacial cleft (NSOFC) is a severe birth defect that occurs early in embryonic development and includes the subtypes cleft palate only (CPO), cleft lip only (CLO) and cleft lip with cleft palate (CLP). Given a lack of specific genetic factor analysis for CPO and CLO, the present study aimed to dissect the landscape of genetic factors underlying the pathogenesis of these two subtypes using 6,986 cases and 10,165 controls. By combining a genome-wide association study (GWAS) for specific subtypes of CPO and CLO, as well as functional gene network and ontology pathway analysis, we identified 18 genes/loci that surpassed genome-wide significance (P < 5 × 10-8) responsible for NSOFC, including nine for CPO, seven for CLO, two for both conditions and four that contribute to the CLP subtype. Among these 18 genes/loci, 14 are novel and identified in this study and 12 contain developmental transcription factors (TFs), suggesting that TFs are the key factors for the pathogenesis of NSOFC subtypes. Interestingly, we observed an opposite effect of the genetic variants in the IRF6 gene for CPO and CLO. Moreover, the gene expression dosage effect of IRF6 with two different alleles at the same single-nucleotide polymorphism (SNP) plays important roles in driving CPO or CLO. In addition, PAX9 is a key TF for CPO. Our findings define subtypes of NSOFC using genetic factors and their functional ontologies and provide a clue to improve their diagnosis and treatment in the future.

Distinct Basal Brain Functional Activity and Connectivity in the Emotional-Arousal Network and Thalamus in Patients With Functional Constipation Associated With Anxiety and/or Depressive Disorders.

OBJECTIVE: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. METHODS: Sixty-five FC patients and 42 healthy controls (HCs) were recruited, and a hierarchical clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional magnetic resonance imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were used to investigate brain functional differences. RESULTS: Thirty-seven patients were classified as FCAD, and 28 patients were classified as FCNAD; as compared with HC, both groups showed decreased activity (fALFF) in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC), and precuneus; enhanced precentral gyrus-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (pFWE < .05). In comparison with FCNAD/HC, the FCAD group also had decreased fALFF in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/precentral gyrus-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated that the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD. CONCLUSIONS: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD, potentially providing important clues for improving treatment strategies.

Can the low and high b-value distribution influence the pseudodiffusion parameter derived from IVIM DWI in normal brain?

BACKGROUND: Our study aims to reveal whether the low b-values distribution, high b-values upper limit, and the number of excitation (NEX) influence the accuracy of the intravoxel incoherent motion (IVIM) parameter derived from multi-b-value diffusion-weighted imaging (DWI) in the brain. METHODS: This prospective study was approved by the local Ethics Committee and informed consent was obtained from each participant. The five consecutive multi-b DWI with different b-value protocols (0-3500 s/mm2) were performed in 22 male healthy volunteers on a 3.0-T MRI system. The IVIM parameters from normal white matter (WM) and gray matter (GM) including slow diffusion coefficient (D), fast perfusion coefficient (D*) and perfusion fraction (f) were compared for differences among defined groups with different IVIM protocols by one-way ANOVA. RESULTS: The D* and f value of WM or GM in groups with less low b-values distribution (less than or equal to 5 b-values) were significantly lower than ones in any other group with more low b-values distribution (all P <  0.05), but no significant differences among groups with more low b-values distribution (P > 0.05). In addition, no significant differences in the D, D* and f value of WM or GM were found between group with one and more NEX of low b-values distribution (all P > 0.05). IVIM parameters in normal WM and GM strongly depended on the choice of the high b-value upper limit. CONCLUSIONS: Metrics of IVIM parameters can be affected by low and high b value distribution. Eight low b-values distribution with high b-value upper limit of 800-1000 s/mm2 may be the relatively proper set when performing brain IVIM studies.

Predicting pathological subtypes and stages of thymic epithelial tumors using DWI: value of combining ADC and texture parameters.

OBJECTIVES: To explore the value of combining apparent diffusion coefficients (ADC) and texture parameters from diffusion-weighted imaging (DWI) in predicting the pathological subtypes and stages of thymic epithelial tumors (TETs). METHODS: Fifty-seven patients with TETs confirmed by pathological analysis were retrospectively enrolled. ADC values and optimal texture feature parameters were compared for differences among low-risk thymoma (LRT), high-risk thymoma (HRT), and thymic carcinoma (TC) by one-way ANOVA, and between early and advanced stages of TETs were tested using the independent samples t test. Receiver operating characteristic (ROC) curve analysis was performed to determine the differentiating efficacy. RESULTS: The ADC values in LRT and HRT were significantly higher than the values in TC (p = 0.004 and 0.001, respectively), also in early stage, values were significantly higher than ones in advanced stage of TETs (p < 0.001). Among all texture parameters analyzed in order to differentiate LRT from HRT and TC, the V312 achieved higher diagnostic efficacy with an AUC of 0.875, and combination of ADC and V312 achieved the highest diagnostic efficacy with an AUC of 0.933, for differentiating the LRT from HRT and TC. Furthermore, combination of ADC and V1030 achieved a relatively high differentiating ability with an AUC of 0.772, for differentiating early from advanced stages of TETs. CONCLUSIONS: Combination of ADC and DWI texture parameters improved the differentiating ability of TET grades, which could potentially be useful in clinical practice regarding the TET evaluation before treatment. KEY POINTS: • DWI texture analysis is useful in differentiating TET subtypes and stages. • Combination of ADC and DWI texture parameters may improve the differentiating ability of TET grades. • DWI texture analysis could potentially be useful in clinical practice regarding the TET evaluation before treatment.

NTN1 gene was risk to non-syndromic cleft lip only among Han Chinese population.

OBJECTIVE: Genome-wide association studies (GWAS) found NTN1, NOG and the region between CREBBP and ADCY9 were risks to non-syndromic cleft lip with or without cleft palate (NSCL/P). However, the association of single nucleotide polymorphisms (SNPs) in these genes with NSCL/P in Western China is unknown. SUBJECTS AND METHODS: We selected seven SNPs in NTN1, NOG and between CREBBP and ADCY9, and then performed transmission disequilibrium test (TDT), parent-of-origin effect and sliding window haplotype analysis to test the associations among 302 NSCL/P case-parent trios from Western Han Chinese. RESULTS: We found allele G at rs4791774 in NTN1 was significantly overtransmitted among non-syndromic cleft lip only (NSCLO) (p = 0.0067, OR = 1.79, 95% CI: 1.17-2.74); rs4791774 and rs9915089 tightly linked with each other among NSCL/P (D' = 0.87, r2  = 0.67) and haplotypes carrying the risk allele G at rs4791774 were always found to be overtransmitted from parents to cases. Motif analysis indicated that allele G at rs4791774 could greatly alter the affinity of Myc_disc7, so allele G at rs4791774 in NTN1 might modulate C-MYC transcription to participate in the aetiology of NSCLO. CONCLUSIONS: Our study suggested allele G at rs4791774 in NTN1 gene is risk of NSCLO, which could greatly increase the risk to have a baby with cleft.

Usefulness of Volume Perfusion Computed Tomography in Differentiating Histologic Subtypes of Thymic Epithelial Tumors.

PURPOSE: This study aimed to evaluate the usefulness of volume perfusion computed tomography (VPCT) parameters in differentiating the World Health Organization subtypes of thymic epithelial tumors. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed written consent was obtained. Fifty-one thymic epithelial tumor patients confirmed by histopathological analysis underwent conventional CT and a 48-second VPCT scan of the tumor bulk before any treatment. The VPCT parameters (blood volume [BV], blood flow [BF], mean transit time [MTT], and permeability [PMB]) based on volume of interest (VOI) or region of interest (ROI) were compared for differences among low-risk thymomas (LRTs; types A, AB, and B1), high-risk thymomas (HRTs; types B2 and B3) and thymic carcinomas (TCs) by one-way analysis of variance. RESULTS: The BVVOI, PMBVOI, BVROI, and PMBROI values in LRT were significantly higher than the values from HRT and thymic carcinoma (BVVOI: 13.75, 6.17, and 5.48 mL/100 mL; PMBVOI: 22.47, 9.56, and 13.37 mL/100 mL/min; BVROI: 14.75, 6.87, and 6.06 mL/100 mL; PMBROI: 24.05, 9.79, and 15.63 mL/100 mL/min, respectively; all P < 0.05/3). However, the BFVOI, MTTVOI, BFROI, and MTTROI values did not differ between LRT and HRT or thymic carcinoma groups (P > 0.05/3). CONCLUSIONS: These results suggest that VPCT could be useful in differentiating LRTs from HRTs and TCs preoperatively.

Research of correlation between personality traits and hormones with the nature of pulmonary nodules.

Background: Rising rates of lung cancer screening have contributed to an increase in pulmonary nodule diagnosis rates. Studies have shown that psychosocial factors and hormones have an impact on the development of the oncological diseases. Therefore, we conducted this study to explore the potential relationship between pulmonary nodules pathology and patient personality traits and hormone levels. Methods: This study enrolled 245 individuals who had first been diagnosed with pulmonary nodules in Tangdu Hospital and admitted for surgery. The personality profile of these patients was analyzed on admission using the C-Type Behavioral Scale and hormone levels were measured in preoperative serum samples. Associations between nodule pathology, personality scores, and hormone levels， were then assessed through Statistical methods analysis. Results: Behavioral scale analyses revealed significant differences four items, including depression, anger outward, optimism, and social support (P< 0.05). Specifically, patients with higher depression scores were more likely to harbor malignant pulmonary nodules, as were patients with lower levels of anger outward, social support, and optimism. Univariate analyses indicated that nodule pathology was associated with significant differences in nodule imaging density, CT value, testosterone levels, and T4 levels(P< 0.05), and logistic regression analyses revealed pulmonary nodule imaging density and T4 levels to be significant differences of nodule pathology. Conclusion: The results showed a significant association between nodules pathology and the personality characteristics of the patients (depression, anger outward, optimism, social support), the patients' T4 levels and the imaging density of the nodules.

A retrospective study of traumatic temporal hollowing and treatment with titanium mesh.

In this study, temporal hollowing was classified into primary and secondary traumatic temporal hollowing according to etiology. This was done to analyze the relationship between the nature of different fractures and temporal hollowing. The options for prophylaxis and treatment for temporal hollowing were explored. Data from 428 patients with zygomatic bone and arch fractures between 2004 and 2009 were analyzed retrospectively. The results showed that the incidences of primary and secondary traumatic temporal hollowing were 6.1% and 52.4%, respectively. Moreover, as the severity of fractures increased, the incidence of primary and secondary temporal hollowing increased. A follow-up study of titanium mesh implantation showed that titanium mesh reconstruction resulted in good cosmetic repair without serious complications. Thus, the internal fixation of primary fractures as well as titanium mesh implantation is recommended for patients with serious fractures to reduce the incidence of postoperative temporal hollowing and avoid secondary operations.

Brain structural changes in regions within the salience network in patients with functional constipation.

Functional constipation (FCon) is one of the common functional gastrointestinal disorders (FGID). Previous studies reported alterations in cortical morphometry as well as changes in white matter (WM) fiber tracts and thalamo-limbic/parietal structural connectivity (SC). However, whether patients with FCon are implicated in changes in gray matter (GM) volume and associated SC remains unclear. Voxel-based morphometry (VBM) was first employed to examine differences in GM volume between 48 patients with FCon and 52 healthy controls (HC). Diffusion tensor imaging (DTI) with probabilistic tractography analysis was then employed to explore alterations in SC of these regions. Results showed abdominal symptoms were positively correlated with anxiety (SAS). Two sample t-test showed patients with FCon had decreased GM volumes in the right middle frontal gyrus (MFG_R), left insula (INS_L), and anterior cingulate cortex (ACC, PFWE < 0.05) which were negatively correlated with abdominal symptoms and difficulty of defecation respectively. Seed-based SC analysis showed patients with FCon had decreased fractional anisotropy of the ACC-right MFG and bilateral INS-MFG tracts. These findings reflect FCon is associated with changes in GM volumes and corresponding SC in brain regions within the salience network.

White-matter microstructural alterations in patients with functional constipation: A tract-based spatial statistics study.

BACKGROUND: Highly prevalent functional constipation (FC) belongs to the category of functional gastrointestinal disorders. Neuroimaging studies have demonstrated brain functional and morphometric changes in patients with FC. However, whether FC is associated with white-matter (WM) microstructural alterations remains unclear. METHODS: Diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) were introduced to investigate WM microstructural changes as calculated by fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) in 26 FC patients and 31 healthy controls. KEY RESULTS: Patients with FC relative to healthy controls had significantly decreased FA with increased MD/RD in the genu (GCC) and body (BCC) of the corpus callosum, right cingulum (Cing), bilateral anterior corona radiata (ACR), bilateral superior corona radiata (SCR), and left posterior corona radiata (PCR) (pFWE  < 0.05). Between-group difference was only in the left SCR and PCR when regressing out anxiety and depression as covariates. CONCLUSIONS AND INFERENCES: These WM tracts are mainly responsible for sensory and emotional information communication and corresponding functional integration; thus, our findings indicate an association between FC and WM microstructural abnormalities in regions involved with visceral afferent and emotional-arousal processing. Alterations in WM microstructures including the CC, cingulum, and ACR are more related to psychological symptoms than constipation, which might have greater impact on brain structures.

Altered Functional Connectivity Within and Between Salience and Sensorimotor Networks in Patients With Functional Constipation.

Functional constipation (FCon) is a common functional gastrointestinal disorder. A considerable portion of patients with FCon is associated with anxiety/depressive status (FCAD). Previous neuroimaging studies mainly focused on patients with FCon without distinguishing FCAD from FCon patients without anxiety/depressive status (FCNAD). Differences in brain functions between these two subtypes remain unclear. Thus, we employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory method to investigate differences in brain network connectivity and topology in 41 FCAD, 42 FCNAD, and 43 age- and gender-matched healthy controls (HCs). FCAD/FCNAD showed significantly lower normalized clustering coefficient and small-world-ness. Both groups showed altered nodal degree/efficiency mainly in the rostral anterior cingulate cortex (rACC), precentral gyrus (PreCen), supplementary motor area (SMA), and thalamus. In the FCAD group, nodal degree in the SMA was negatively correlated with difficulty of defecation, and abdominal pain was positively correlated with nodal degree/efficiency in the rACC, which had a lower within-module nodal degree. The salience network (SN) exhibited higher functional connectivity (FC) with the sensorimotor network (SMN) in FCAD/FCNAD, and FC between these two networks was negatively correlated with anxiety ratings in FCAD group. Additionally, FC of anterior insula (aINS)-rACC was only correlated with constipation symptom (i.e., abdominal pain) in the FCNAD group. In the FCAD group, FCs of dorsomedial prefrontal cortex-rACC, PreCen-aINS showed correlations with both constipation symptom (i.e., difficulty of defecation) and depressive status. These findings indicate the differences in FC of the SN-SMN between FCAD and FCNAD and provide neuroimaging evidence based on brain function, which portrays important clues for improving new treatment strategies.

Abnormalities in the thalamo-cortical network in patients with functional constipation.

Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID); neuroimaging studies have shown brain functional abnormalities in thalamo-cortical regions in patients with FGID. However, association between FCon and topological characteristics of brain networks remains largely unknown. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory approach to investigate functional brain topological organization in 42 patients with FCon and 41 healthy controls (HC) from perspectives of global, regional and modular levels. Results showed patients with FCon had a significantly lower normalized clustering coefficient and small-worldness, implying decreased brain functional connectivity. Regions showed altered nodal degree and efficiency mainly located in the thalamus, rostral anterior cingulate cortex (rACC), and supplementary motor area (SMA), which are involved in somatic/sensory, emotional processing and motor-control. For the modular analysis, thalamus, rACC and SMA had an aberrant within-module nodal degree and nodal efficiency, and thalamus-related network exhibited abnormal interaction with the limbic network (amygdala and hippocampal gyrus). Nodal degree in the thalamus was negatively correlated with difficulty of defecation, and nodal degree in the rACC was negatively correlated with sensation of incomplete evacuation. These findings indicated that FCon was associated with abnormalities in the thalamo-cortical network.

Functional constipation is associated with alterations in thalamo-limbic/parietal structural connectivity.

BACKGROUND: Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID) with a high prevalence in clinical practice. Previous studies have identified that FCon is associated with functional and structural alterations in the primary brain regions involved in emotional arousal processing, sensory processing, somatic/motor-control, and self-referential processing. However, whether FCon is associated with abnormal structural connectivity (SC) among these brain regions remains unclear. METHODS: We selected the brain regions with functional and structural abnormalities as seed regions and employed diffusion tensor imaging (DTI) with probabilistic tractography to investigate SC changes in 29 patients with FCon and 31 healthy controls (HC). KEY RESULTS: Results showed lower fractional anisotropy (FA) in the fibers connecting the thalamus, a region involved in sensory processing, with the amygdala (AMY), hippocampal gyrus (HIPP), precentral (PreCen) and postcentral gyrus (PostCen), supplementary motor area (SMA) and precuneus in patients with FCon compared with HC. FCon had higher mean diffusivity (MD) and radial diffusivity (RD) in the thalamus connected to the AMY and HIPP. In addition, FCon had significantly increased RD of the thalamus-SMA tract. Sensation of incomplete evacuation was negatively correlated with FA of the thalamus-PostCen and thalamus-HIPP tracts, and there was a negative correlation between difficulty of defecation and FA of the thalamus-SMA tract. CONCLUSIONS AND INFERENCES: These findings reflected that FCon is associated with alterations in SC between the thalamus and limbic/parietal cortex, highlighting the integrative role of the thalamus in brain structural network.

Association analysis of GWAS hits and non-syndromic cleft lip with/without palate with cleft alveolar in Han population of western China.

Cleft alveolar is often accompanied by non-syndromic cleft lip with/without palate (NSCL/P), which could seriously affect the growth and development of the maxilla. In this study, we assessed the associations between 47 susceptible SNPs from previous GWASs of NSCL/P and cleft alveolar in Western Han Chinese population. We recruited 228 trios of NSCL/P with cleft alveolar (156 males and 72 females). The 47 SNPs were genotyped by SNPscan method; Hardy-Weinberg equilibrium test, TDT and parent-of-origin effects were analyzed by PLINK; linkage disequilibrium analysis was conducted by Haploview software. TDT analysis revealed FOXE1 rs894673 (P = 0.0071, ORtransmission = 0.35, 95% CI: 0.16-0.78) and rs3758249 (P = 0.0071, ORtransmission = 0.35, 95% CI: 0.16-0.78) were associated with NSCL/P accompanied cleft alveolar bone. Parent-of-origin effect analysis revealed a paternal special under-transmission of allele A at rs894673 (P = 0.039), allele T at rs3759249 (P = 0.039), and allele T at rs4460498 (P = 0.039) of FOXE1. Allele A at rs987525 showed a significant paternal over-transmission (P = 0.0077). Pairwise LD analysis showed strong LD among rs894673, rs3759249 and rs4460498 (r2 > 0.95, D' = 1). To conclude, our findings indicated that FOXE1 is the susceptible gene for cleft alveolar accompanied by NSCL/P.

Cortical morphometry alterations in brain regions involved in emotional, motor-control and self-referential processing in patients with functional constipation.

Functional constipation (FC) is a common functional gastrointestinal disorder (FGID). Neuroimaging studies on patients with FC showed brain functional abnormalities in regions involved in emotional process modulation, somatic and sensory processing and motor control. Brain structural imaging studies in patients with FGID have also shown disease-related alterations in cortical morphometry, but whether and how FC affects brain structure remains unclear. Structural Magnetic Resonance Imaging and surface-based morphometry analysis were used to investigate the impact of FC on cortical morphometry in 29 patients with FC and 29 healthy controls (HC). Results showed that patients with FC compared to HC had significantly decreased cortical thickness in the left middle frontal gyrus (MFG), dorsomedial (DMPFC) and ventromedial prefrontal gyrus (VMPFC), right dorsal anterior cingulate cortex (dACC), left orbitofrontal cortex (OFC), posterior cingulate cortex (PCC)/precuneus, middle temporal gyrus (MTG), and supplementary motor area (SMA) (P < 0.01). Correlation analysis showed that sensation of incomplete evacuation was negatively correlated with cortical thickness in the SMA (P < 0.0001). In addition, patients with FC also had decreased cortical volume than HC in the MTG, precentral gyrus (PreCen) and precuneus/cuneus (P < 0.01), as well as decreased cortical surface area in the PreCen (P < 0.01). No correlation was found between cortical volume/surface area and behavioral measures. These findings suggest that patients with FC are associated with cortical morphometric abnormalities in brain regions implicated in somatic/motor-control, emotional processing and self-referential processing.

Exon sequencing reveals that missense mutation of PBX1 gene may increase the risk of non-syndromic cleft lip/palate.

OBJECTIVE: Non-syndromic oral cleft (NSOC) is one of the most common multifactorial birth defects. A previous animal study showed PBX1 gene knockout mice consequently exhibited complete cleft lip/palate (CL/P). However, little is known about the association between PBX1 and NSOC in humans. This study investigated the role of the PBX1 gene in NSOC in the Han Chinese population. METHODS: In all, 287 NSOCs were recruited for this study. First, exons in the PBX1 gene were sequenced among 50 non-syndromic cleft lip and palate cases to screen for variations by the Sanger sequencing method. Then, we selected four SNPs to replicate among 237 NSOC trios and analyzed the data by using TDT and parent of origin effect methods. RESULTS: Exon sequencing identified six variants of the PBX1 gene. Among them, four variants were common variants. TDT analysis revealed allele G at rs2275558 and allele T at rs3835581 were over-transmitted in NSCL/P (P=0.039 and 0.038, respectively), which could increase the risk for NSCL/P. Parent of origin effect analysis indicated that allele G at rs2275558 was paternally over-transmitted for NSCL/P (P=0.0091). CONCLUSION: This is the first report that the PBX1 gene is associated with NSCL/P, which indicates that it is a promising candidate gene for NSCL/P.