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Biochemical liver function tests are important methods to determine liver function in clinical practice， but abnormal liver biochemical parameters are not completely equivalent to liver damage. Some genetic and immune factors can also cause abnormal liver biochemical parameters， but with good prognosis in most cases. This article summarizes the causes of some benign abnormal liver biochemical parameters， so as to help clinicians to broaden their thinking of diagnosis and treatment， take into account genetic and immune factors， and avoid misdiagnosis and mistreatment.
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Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
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Primary biliary cholangitis (PBC) is a chronic intrahepatic cholestatic disease. This article summarizes and reviews the histopathological features of PBC and the role of pathological examination in the diagnosis and treatment of PBC, as well as the role of pathology in staging and prognosis, the diagnosis of atypical PBC and overlap syndrome, the analysis of reasons for poor response to ursodeoxycholic acid, and identification of diseases or exclusion of other comorbidities, so as to improve the awareness of the role of pathological examination in PBC among clinicians.
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Autoimmune hepatitis has become the main type of non-infectious hepatitis in China. This article summarizes its characteristic manifestations and the current status of diagnosis and treatment and points out that pathological histology plays an indispensable role in the diagnosis and treatment of autoimmune hepatitis.
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Liver cirrhosis is the final stage of various chronic liver diseases, and the common etiologies of liver cirrhosis include chronic viral hepatitis, nonalcoholic fatty liver disease, autoimmune liver diseases, and inherited metabolic liver disease. An accurate etiological diagnosis is an important prerequisite for etiological treatment. Unexplained liver cirrhosis refers to liver cirrhosis without a definite etiology after medical history inquiry, physical examination, and auxiliary examination. At present, liver histopathological examination is a gold standard for the diagnosis of liver cirrhosis and an important basis for exploring the etiology of liver cirrhosis. It may help with the etiological diagnosis of unexplained liver cirrhosis to evaluate the pattern of liver fibrosis, the type of inflammatory injury, and related pathological changes with reference to a comprehensive analysis of related medical history, signs, laboratory examination, and radiological examination. This article reviews the pathological features and diagnostic thinking of unexplained liver cirrhosis.
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Histopathological evaluation based on liver biopsy is required to make a confirmed diagnosis of nonalcoholic fatty liver disease, differentiate nonalcoholic fatty liver (NAFL) from nonalcoholic steatohepatitis (NASH), and perform the grading and scoring of disease severity, while hematological and radiological examinations are often used in clinical practice. Although there have been a large number of studies on noninvasive models for fibrosis assessment and disease diagnosis in nonalcoholic fatty liver disease, the sensitivity and specificity of such models need to be further improved. This article reviews the main pathological features of NAFL and NASH, fibrosis and grading/staging/scoring systems, and the pathological diagnosis of NASH liver cirrhosis, in order to improve the awareness of the histological diagnosis of such disease among clinicians
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Liver histopathology plays an important role in the grading and staging of liver diseases and the etiological evaluation of unexplained liver diseases. Clinicians should fully understand the indications and contraindications for liver biopsy, the pathological features of liver diseases, the position and role of liver histopathology, and the importance of clinicopathological communication. This article reviews the above issues to help clinicians better apply liver histopathology as an invasive diagnostic method.
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Objective To investigate the etiological and clinical features of patients with unexplained liver disease manifesting as isolated jaundice and the value of whole-exome sequencing in the diagnosis of such diseases. Methods A retrospective analysis was performed for the clinical data of the patients who attended Nanjing Second Hospital due to unexplained liver disease and underwent whole-exome sequencing from February 2017 to December 2021, and according to liver function parameters and imaging data, all cases were classified based on clinical phenotype and were diagnosed based on the whole-exome sequencing report. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. Results A total of 519 patients underwent whole-exome sequencing, among whom 102 patients with missing or incomplete clinical data were excluded, and finally 417 patients were included in analysis, among whom 91(91/417, 21.82%) had the manifestation of isolated jaundice. The etiology of jaundice was not determined by whole-exome sequencing in 8 patients (8/91, 8.79%). With reference to genetic testing results, 83 patients (83/91, 91.21%) had a confirmed diagnosis, among whom there were 68 patients with hereditary hyperbilirubinemia (68/91, 74.72%), 3 patients with hereditary spherocytosis (3/91, 3.30%), 2 patients with pyruvate kinase deficiency (2/91, 2.20%), and 10 patients with UGT1A1 gene disease combined with other diseases (10/91, 10.99%). Hereditary hyperbilirubinemia was the main etiology, and there were 61 patients with UGT1A1 gene disease (61/91, 67.03%), 5 patients with Dubin-Johnson syndrome (5/91, 5.49%) and 2 patients with Rotor syndrome (2/91, 2.20%). There was a significant difference in indirect bilirubin/total bilirubin ratio between the patients with the different diagnoses above ( H =22.835, P < 0.05), and the patients with UGT1A1 gene disease and other diseases had a significantly higher level of total bilirubin than those with UGT1A1 gene disease alone [95.8 (37.5-187.1) μmol/L vs 51.4 (34.8-267.1) μmol/L, Z =-2.372, P =0.018]. Conclusion Whole-exome sequencing can help with the diagnosis of most cases of unexplained liver disease manifesting as isolated jaundice. Hereditary hyperbilirubinemia is the main etiology, and UGT1A1 gene disease is the most common disease. Whole-exome sequencing can assist the clinical diagnosis of unexplained liver disease manifesting as isolated jaundice.
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Objective To investigate the clinical and pathological features of progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods A retrospective analysis was performed for 1326 patients with unexplained liver disease who attended Nanjing Second Hospital from January 2017 to December 2019, among whom 8 patients were diagnosed with PFIC3 based on clinical/pathological manifestation and gene sequencing results (1 patient did not undergo liver biopsy due to contraindication). Clinical, laboratory, imaging, and pathological findings were analyzed and a literature review was performed for the pathology of ABCB4-related diseases to summarize the clinical and pathological features of PFIC-3. Results Among the 8 patients with PFIC3, there were 5 male patients and 3 female patients, with a median age of 29.5 years. Of all 8 patients, 4 (50%) manifested as chronic cholestasis and 4 (50%) manifested as biliary cirrhosis, among whom 3 (75%) had the manifestation of portal hypertension. As for biochemical examination, 75% (6/8) had an increase in alkaline phosphatase, and 100% (8/8) had an increase in gamma-glutamyl transpeptidase. As for imaging examination, 50% (4/8) had cholecystitis, 25% (2/8) had gallstones, 25% (2/8) had bile duct dilatation, 75% (6/8) had splenomegaly, and 25% (2/8) had liver cirrhosis. As for liver biopsy, all 7 patients manifested as bile duct injury and/or reduction, and 57.1% (5/7) had absence of the bile duct. Multidrug resistance P-glycoprotein 3 (MDR3) immunohistochemical staining showed normal expression in 42.9% (3/7) of the patients and reduced expression in 57.1% (4/7) of the patients. Literature review obtained 17 articles with a description of the bile duct or MDR3 immunohistochemistry. Among the 7 patients with low phospholipid-associated cholelithiasis, 71.4% (5/7) had normal bile duct, 14.3% (1/7) had bile duct reduction, and 14.3% (1/7) had absence of the bile duct; among the 6 patients with intrahepatic cholestasis of pregnancy, 16.7% (1/6) had normal bile duct, 50% (3/6) had bile duct reduction, and 33.3% (2/6) had absence of the bile duct; among the 8 patients with PFIC3, 25% (2/8) had bile duct reduction and 75% (6/8) had absence of bile duct; among the 21 patients with PFIC3, 9.5% (2/21) had normal expression of MDR3, 23.8% (5/21) had a reduction in the expression of MDR3, and 66.7% (14/21) had absence of the expression of MDR3. Conclusion PFIC3 mainly manifests as cholestasis, cholelithiasis, and hepatic fibrosis. Pathological manifestation includes bile duct injury and bile duct reduction or absence of the bile duct in severe cases, and the degree of injury is associated with disease severity. MDR3 immunohistochemistry may show normal expression, reduced expression, or absence of expression, and diagnosis cannot be excluded in patients with normal expression. Genetic testing can be performed for diagnosis when necessary.
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Objective:A case-control association analysis was performed to investigate if the single nucleotide polymorphisms (SNPs) of N-cadherin(CDH2) gene is implicated in schizophrenia in a Han Chinese population.Methods:A total of 528 patients with paranoid schizophrenia and 528 healthy controls were recruited from northern Henan province to analyze 25 SNPs located in CDH2 gene.The clinical symptoms of 267 first-episode schizophrenia patients were evaluated with positive and negative syndrome scale (PANSS), and the correlation between CDH2 gene and clinical symptoms was analyzed by SNPStats software online.Results:Allele frequencies of rs9951577 and rs1231268 were significantly correlated with schizophrenia( P<0.05), genotype frequency of rs1639387 was significantly correlated with schizophrenia( P=0.044). After gender classification, SNPs rs1789470 and rs28365328 were found to be significantly correlated with schizophrenia in female patients ( P=0.044, 0.019). In addition, the study found that CDH2 was correlated with the clinical characteristics of schizophrenia( P<0.05), and the negative factor score of patients between GG type rs1231268 and the other two genotypes (AG+ AA) ((21.12±8.41) vs (18.87±7.52)) was statistically significant ( P<0.05). Conclusion:CDH2 gene may be one of the susceptibility genes to SZ, and has definite correlation with clinical negative symptoms.
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ABCB4-related disease is the syndrome of bile secretion disorder caused by gene mutations and can cause bile duct injury, portal hypertension, and liver cirrhosis in clinical practice. With the development of genetics and gene sequencing techniques in recent years, more and more mutation sites have been identified; however, since this is a relatively complex disease, the pathogenicity and pathogenic mechanism of mutations remain unclear. Meanwhile, since this disease is rare, it is difficult to determine the pathogenicity of ABCB4 mutations based on basic research or clinical data. Therefore, it is urgent to establish the association between ABCB4 genotypes and phenotypes and construct a complete system in basic research and clinical practice.
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Based on liver histology, drug-induced liver injury (DILI) is classified as various pathological types of inflammatory necrosis, cholestasis, fatty degeneration and fatty liver disease, vascular injury, and minimal lesion. Histopathological examination is required for further differential diagnosis in suspected cases of DILI, liver injury that cannot be explained by DILI monogenesis, DILI cases with a history of exposure to various drugs in which the specific drug causing liver injury cannot be determined, DILI cases with unsatisfactory treatment outcome, and chronic DILI, and histopathological examination can also be used to evaluate the severity and prognosis of DILI. Since liver lesions are unevenly distributed in DILI, adequate tissue samples are needed to reduce sampling error. The histopathological manifestation of liver injury diseases has the features of "one cause with multiple results and one result with multiple causes", and a combination of pathological examination and clinical symptoms can help to make a confirmed diagnosis, suggesting that clinicopathological discussion is of great importance in the histological diagnosis of DILI.
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Objective:To investigate the potentially inappropriate medication(PIM)among elderly patients with chronic diseases in Shanghai communities and related influence factors.Method:Six community Health service Centers were choosen using stratified sampling. Total 968 elderly patients with chronic diseases who visited to the outpatient clinic of Shanghai Community Health Service Centers from July to August 2018 were included in the study. The PIM was investigated according to the 2015 Beers criteria. The χ 2 test and multivariate logistic regression model were used to analyze factors related to the PIM. Results:The survey showed that 317 elderly patients had PIM with 412 person-doses. In 134 person-doses, the PIM was unrelated to the disease; in 18 person-doses, PIM was caused by interaction of drug with disease/symptoms; in 259 person-doses PIM was related to the drugs that should be cautiously used for elderly; only in 1 person-dose the PIM was caused by the interaction between drugs. The drugs with the highest proportion of PIM were diuretics, benzodiazepines and aspirin. There were significant differences in age, kinds of diseases, kinds of drugs and times of visiting community health service centers between elderly patients with PIM and those without PIM (χ 2=42.28, 35.51, 46.47, 38.46; all P<0.05). The main PIM-related factors were age, kinds of diseases, kinds of drugs and times of visiting community health service centers. Conclusion:The study shows that the prevalence of PIM among elderly chronic diseases patients in Shanghai communities is relatively high, which is associated with the age, kinds of diseases, kinds of drugs and times of visiting community health service centers.
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[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].
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Objective:To explore the functional connections of the whole brain and the two hemispheres in patients with obsessive-compulsive disorder (OCD).Methods:Twenty-six patients with obsessive-compulsive disorder(patients group) and thirty-seven healthy controls matched in gender, age and education(control group) were enrolled.All the participants accepted the resting-state functional magnetic resonance (rs-fMRI) scan.Based on DPABI and REST software, degree centrality (DC) and voxel - mirrored homotopic connectivity (VMHC) approaches were used to explore the pattern of functional connection in OCD.Results:Compared with the control group, the DC values in the right posterior cerebellar lobe(MNI: x, y, z=45, -87, -12), left precentral gyrus(MNI: x, y, z=-54, 9, 39), left inferior parietal lobule(MNI: x, y, z=-48, -51, 42), right anterior cingulate cortex(MNI: x, y, z=3, 18, 48) were significantly higher( t values were 5.75, 5.26, 5.28 and 5.16, respectively), and the DC values in the left inferior frontal gyrus(MNI: x, y, z=-36, 9, 30) were significantly lower( t value was -6.65) in patients group.The VMHC values in bilateral posterior cerebellar lobe(MNI: x, y, z=±51, -69, -33), bilateral inferior parietal lobule(MNI: x, y, z=±48, -51, 54), bilateral anterior cingulate cortex(MNI: x, y, z=±3, 21, 45)in patients group were significantly higher that those in control group( t values were 5.19, 5.19, 5.02, 5.02, 5.15 and 5.15, respectively). The DC and VMHC values in patients group were not significantly correlated with clinical symptoms(-0.23< r<0.19, P>0.05). Conclusion:OCD patients have abnormal connections between key brain network nodes and relevant brain regions, and functional connections have increased among multiple cerebral hemispheres.
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Objective@#To understand the etiology of hepatopathy of unknown etiology in patients undergoing liver biopsy.@*Methods@#Demographic data and pathological examination reports of patients with hepatopathy of unknown etiology who underwent liver biopsy examination at outpatient and inpatient of the Second Hospital of Nanjing between January 2017 and June 2018 were retrospectively collected. All liver histopathological sections combined with clinical and pathological features based on liver biopsy examinations were diagnosed by a reputed clinician and a pathologist.@*Results@#A total of 470 cases with hepatopathy of unknown etiology who underwent liver biopsy were enrolled. Of these, 425 cases (90.4%) had a definite diagnosed disease after comprehensive analysis of pathological and clinical data. The diagnosis of hepatopathy of unknown etiology included 11 diseases: 90 cases with autoimmune hepatitis had autoimmune liver disease (19.1%), 38 cases had primary biliary cholangitis (8.1%), 43 cases with overlap syndrome of autoimmune hepatitis had primary biliary cholangitis (9.1%), 118 cases had drug-induced liver injury (25.1%), 75 cases had nonalcoholic fatty liver disease (NAFLD) (16.0%), 12 cases had alcoholic liver disease (2.6 cases) %), 15 cases (3.2%) had vascular liver disease, 7 cases (1.5%) had hereditary metabolic liver disease, 5 cases (1.1%) had other systemic diseases, 16 cases (3.4%) had more than two kinds of liver diseases, and 6 cases (1.3%) had others rare liver diseases.@*Conclusion@#Over 90% cause of the hepatopathy of unknown etiology in the long run can be determined, and the main causes are autoimmune liver disease, drug-induced liver injury, and nonalcoholic fatty liver disease, which needs multidisciplinary cooperation to diagnose, and clinicians need to master the basic and clinical knowledge of liver diseases as well as liver pathology, hepatobiliary imaging, and genetics.
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Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.
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Objective To investigate the spontaneous activity of brain neurons in patients with obsessive－compulsive disorder (OCD) under resting state. Methods Forty－eight OCD patients and 50 age－, gender－ and year of education－matched normal controls were enrolled. All the subjects underwent 3.0 T fMRI to acquire resting state brain image. The brain regions with significant differences in amplitude of low－frequency fluctuation (ALFF) between patients and controls were analyzed. Whole－brain functional connectivity (FC) were analyzed using the brain regions with significant differences as seed points, and the correlation between brain regions with significant differences in ALFF and FC analysis and obsessive－compulsive symptoms was analyzed. Results Compared to the control group, the ALFF of left dorsolateral prefrontal cortex increased in patients with OCD (t=4.305, P＜0.001). Compared to the controls, the analysis of whole－brain FC (based on MNI template) with the left dorsolateral prefrontal cortex as the regions of interest showed that the FC strength between the left dorsolateral prefrontal cortex and right orbital inferior frontal cortex (t=3.897, P＜0.001), left anterior cingulate cortex (t=3.370, P＜0.001), right anterior cingulate cortex (t=4.299, P＜0.001), left middle cingulate cortex (t=3.220, P＜0.001), right middle cingulate cortex (t=4.607, P＜0.001) enhanced; the FC strength between the left dorsolateral prefrontal cortex and the left opercular part of inferior frontal gyrus (t=－4.630, P＜0.001) weakened in patients with OCD. The FC between the left dorsolateral prefrontal cortex and the left opercular part of inferior frontal gyrus was negatively correlated with obsessions score(r=－0.369, P=0.014), compulsions score (r=－0.392, P=0.009) and total score (r=－0.393, P=0.008) of the Yale－Brown obsessive compulsive scale (Y－BOCS). Conclusion In patients with OCD, spontaneous neural activity of the left dorsolateral prefrontal cortex is enhanced in resting state, and the FC with multiple brain regions is abnormal. The FC strength between the left dorsolateral prefrontal cortex and the left opercular part of inferior frontal gyrus is associated with obsessive－compulsive symptoms.
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Objective Regional homogeneity (ReHo) and functional connectivity (FC) were used to study obsessive-compulsive disorder(OCD),and to explore the mechanism of OCD in resting state.Method Resting-state functional magnetic resonance imaging (RS-fMRI) was performed in 55 patients with OCD (OCD group) and 50 normal controls (control group) matched by sex,age,nationality and education.The data and screening abnormal brain areas were analyzed and compared by DPARSFA2.3 and Rest software in OCD group.Whole brain FC analysis was performed with abnormal brain areas as seed points.Result Compared with the control group,ReHo in right thalamus (MNI:x=9,y=-24,z=6,t=4.3217) and left superior marginal gyrus (MNI:x =-45,y =-30,z =27,t =3.6320) increased and ReHo in right caudate nucleus (MNI:x=3,y=15,z=9,t=-3.1687) decreased in obsessive-compulsive disorder group,and the difference was statistically significant(P＜0.05).Using left superior marginal gyrus,fight thalamus and right caudate nucleus as seed voxels,the whole brain FC analysis showed that there were abnormal functional connections between bilateral cerebellar foot 1/2 area and left supramarginal gyrus,right thalamus and right caudate nucleus (P＜0.05) and the left supramarginal gyrus-bilateral cerebellum feet 1 area-right thalamic circuit and left supramarginal gyrus-bilateral cerebellum feet 1,2-right caudate nucleus-right thalamic circuit existed in 0CD group.Conclusion The left supramarginal gyrus-bilateral cerebellum feet 1 area-right thalamic circuit and left supramarginal gyrus-bilateral cerebellum feet 1,2-right caudate nucleus-right thalamic circuit may play an important role in the mechanism of OCD.
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Objective@#To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.@*Methods@#Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.@*Results@#132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death.@*Conclusion@#Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.