Volumes of hippocampal subfields suggest a continuum between schizophrenia, major depressive disorder and bipolar disorder.

Objective: There is considerable debate as to whether the continuum of major psychiatric disorders exists and to what extent the boundaries extend. Converging evidence suggests that alterations in hippocampal volume are a common sign in psychiatric disorders; however, there is still no consensus on the nature and extent of hippocampal atrophy in schizophrenia (SZ), major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study was to verify the continuum of SZ - BD - MDD at the level of hippocampal subfield volume and to compare the volume differences in hippocampal subfields in the continuum. Methods: A total of 412 participants (204 SZ, 98 MDD, and 110 BD) underwent 3 T MRI scans, structured clinical interviews, and clinical scales. We segmented the hippocampal subfields with FreeSurfer 7.1.1 and compared subfields volumes across the three diagnostic groups by controlling for age, gender, education, and intracranial volumes. Results: The results showed a gradual increase in hippocampal subfield volumes from SZ to MDD to BD. Significant volume differences in the total hippocampus and 13 of 26 hippocampal subfields, including CA1, CA3, CA4, GC-ML-DG, molecular layer and the whole hippocampus, bilaterally, and parasubiculum in the right hemisphere, were observed among diagnostic groups. Medication treatment had the most effect on subfields of MDD compared to SZ and BD. Subfield volumes were negatively correlated with illness duration of MDD. Positive correlations were found between subfield volumes and drug dose in SZ and MDD. There was no significant difference in laterality between diagnostic groups. Conclusion: The pattern of hippocampal volume reduction in SZ, MDD and BD suggests that there may be a continuum of the three disorders at the hippocampal level. The hippocampus represents a phenotype that is distinct from traditional diagnostic strategies. Combined with illness duration and drug intervention, it may better reflect shared pathophysiology and mechanisms across psychiatric disorders.

Ground Movement in the Hanging Wall of Underground Iron Mines with Steeply Dipping Discontinuities: A Case Study.

To ensure the safety of underground mining activities and effectively protect the surface production facilities and houses of the nearby residents, the ground movement caused by the sublevel caving method needs to be studied. In this work, the failure behaviors of the surface and drift of the surrounding rock were investigated based on the results of in situ failure investigations, monitoring data, and engineering geological conditions. The results were then combined with theoretical analysis to reveal the mechanism responsible for the movement of the hanging wall. Driven by the in situ horizontal ground stress, horizontal displacement plays an imperative role in both the movement of the ground surface and underground drifts. Accelerated movement is found to occur in the ground surface which coincides with the occurrence of drift failure. Failure occurs in the deep rock masses and then gradually propagates to the surface. The steeply dipping discontinuities are the main reason for the unique ground movement mechanism in the hanging wall. As steeply dipping joints cut through the rock mass, the rock surrounding the hanging wall can be modeled as cantilever beams subjected to in situ horizontal ground stress and lateral stress due to caved rock. This model can be used to obtain a modified formula for toppling failure. Also, a mechanism of fault slipping was proposed, and the condition required for fault slipping was obtained. Based on the failure mechanism of steeply dipping discontinuities, the ground movement mechanism was proposed considering the horizontal in situ ground stress and caved rock mass: slippage of fault F3, slippage of fault F4, and toppling of rock columns. Based on the unique ground movement mechanism, the goaf surrounding rock mass could be divided into six zones: a caved zone, a failure zone, a toppling-slipping zone, a toppling-deformation zone, a fault-slipping zone, and a movement-deformation zone.

Electroconvulsive therapy efficacy in adolescents with mental illness: A retrospective comparison.

Background: There is limited evidence on the efficacy of electroconvulsive therapy (ECT) in adolescents with mental illness. The present study reported outcomes of adolescents with mental illness treated with ECT aimed at providing evidence for large-scale feasibility. Objectives: The primary objective of this trial was to examine the differences in demographic and clinical data between responders and non-responders. The secondary objective was to determine whether ECT produced differential readmission rates, the burden of oral medication, and social function in responders and non-responders in the long term. Methods: Patients aged 14-18 years diagnosed with schizophrenia (SCZ), major depressive disorder (MDD), or bipolar disorder (BD) who received ECT between 2015 and 2020 were included in the study. Demographic and clinical data were compared, and both short-term and long-term outcomes were assessed: response on the Clinical Global Impressions-Improvement scale and readmission at follow-up. The independent-sample t-test was used to compare the continuous variables and the X 2 test was used to compare the dichotomous variables with statistical significance at P ≤ 0.05. Results: Four hundred ten adolescents (aged 14-18 years, 53.90% female) received ECT for SCZ, MDD, and BD. The response rate for SCZ, MDD, and BD were 65.61, 78.57, and 69.95%, respectively. Both SCZ (P = 0.008) and BD (P = 0.008) groups had a significant elder age in responders than in non-responders. Besides that MDD responders had a significantly larger number of ECT sessions than non-responders (P = 0.046), the study failed to find a significant difference in other ECT parameters. A significantly higher proportion of readmission was found in BD non-responders than in responders (P = 0.029), there was no difference in the rate of readmission in other diagnostic groups. Conclusions: These data suggested that ECT is an effective treatment for adolescents with severe mental illness, and the rate of readmission was low in the long term. The present study supports that large-scale systematic studies are warranted for further investigation of the response rate of ECT for treating adolescents with mental illness.

Aberrant Functional Connectivity of the Orbitofrontal Cortex Is Associated With Excited Symptoms in First-Episode Drug-Naïve Patients With Schizophrenia.

Background: Schizophrenia (SZ) is associated with the highest disability rate among serious mental disorders. Excited symptoms are the core symptoms of SZ, which appear in the early stage, followed by other stages of the disease subsequently. These symptoms are destructive and more prone to violent attacks, posing a serious economic burden to the society. Abnormal spontaneous activity in the orbitofrontal cortex had been reported to be associated with excited symptoms in patients with SZ. However, whether the abnormality appears in first-episode drug-naïve patients with SZ has still remained elusive. Methods: A total of 56 first-episode drug-naïve patients with SZ and 27 healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) and positive and negative syndrome scale (PANSS). First, differences in fractional amplitude of low-frequency fluctuations (fALFF) between first-episode drug-naïve patients with SZ and healthy controls were examined to identify cerebral regions exhibiting abnormal local spontaneous activity. Based on the fALFF results, the resting-state functional connectivity analysis was performed to determine changes in cerebral regions exhibiting abnormal local spontaneous activity. Finally, the correlation between abnormal functional connectivity and exciting symptoms was analyzed. Results: Compared with the healthy controls, first-episode drug-naïve patients with SZ showed a significant decrease in intrinsic activity in the bilateral precentral gyrus, bilateral postcentral gyrus, and the left orbitofrontal cortex. In addition, first-episode drug-naïve patients with SZ had significantly reduced functional connectivity values between the left orbitofrontal cortex and several cerebral regions, which were mainly distributed in the bilateral postcentral gyrus, the right middle frontal gyrus, bilateral paracentral lobules, the left precentral gyrus, and the right median cingulate. Further analyses showed that the functional connectivity between the left orbitofrontal cortex and the left postcentral gyrus, as well as bilateral paracentral lobules, was negatively correlated with excited symptoms in first-episode drug-naïve patients with SZ. Conclusion: Our results indicated the important role of the left orbitofrontal cortex in first-episode drug-naïve patients with SZ and suggested that the abnormal spontaneous activity of the orbitofrontal cortex may be valuable to predict the occurrence of excited symptoms. These results may provide a new direction to explore the excited symptoms of SZ.

Application of Fiber Bragg Grating Sensor Technology to Leak Detection and Monitoring in Diaphragm Wall Joints: A Field Study.

Joints between diaphragm wall panels are weak spots in wall construction. It is essential that potential leak sites are detected prior to excavation. In this study, a novel leak detection and monitoring system is presented that is based on fiber Bragg grating (FBG) sensing technology. A field study was performed in a deep excavation supported by diaphragm walls (in Hohhot, China) to validate the feasibility and effectiveness of the proposed method. Two schemes were trialed; one using pipes made of stainless steel, and one used a pipeless method. The results of the field study are presented and discussed. They show that potential leak sites in the wall joints could be determined prior to excavation using the proposed detection method. Stainless steel is a good material to use to make the detection tube because it can protect the FBG sensors and heating belts from damage and is more sensitive to water leakage. The field study provides good evidence for the feasibility of the new detection system. It also provides valuable experience for the field application of the system and has generated useful data to use in follow-up work.

Identification and functional characterization of novel GDAP1 variants in Chinese patients with Charcot-Marie-Tooth disease.

OBJECTIVE: To identify and characterize the pathogenicity of novel variants in Chinese patients with Charcot-Marie-Tooth disease. METHODS: Multiplex ligation-dependent probe amplification (MLPA) and whole-exome sequencing (WES) were performed in 30 unrelated CMT patients. Minigene assay was used to verify the effect of a novel splicing variant (c.694+1G>A) on pre-mRNA. Primary fibroblast cell lines were established from skin biopsies to characterize the biological effects of the novel variants p.L26R and p.S169fs. The mitochondrial structure was observed by an electron microscope. The expression level of protein was analyzed by Western Blotting. Mitochondrial dynamics and mitochondrial membrane potential (MMP, Δψm) were analyzed via immunofluorescence study. Mitochondrial ATP levels were analyzed via bioluminescence assay. The rate of oxygen consumption was measured with a Seahorse Bioscience XF-96 extracellular flux analyzer. RESULTS: We identified 10 pathogenic variants in three known CMT related genes, including three novel variants (p.L26R, p.S169fs, c.694+1G>A) and one known pathogenic variant (p.R120W) in GDAP1. Further, we described the clinical features of patients carrying pathogenic variants in GDAP1 and found that almost all Chinese CMT patients with GDAP1 variants present axonal type. The effect of c.694+1G>A on pre-mRNA was verified via minigene splice assay. Cellular biological effects showed ultrastructure damage of mitochondrial, reduced protein levels, different patterns of mitochondrial dynamics, decreased mitochondrial membrane potential (Δψm), ATP content, and defects in respiratory capacity in the patient carrying p.L26R and p.S169fs in GDAP1. INTERPRETATION: Our results broaden the genetic spectrum of GDAP1 and provided functional evidence for mitochondrial pathways in the pathogenesis of GDAP1 variants.

Genetic Spectrum and Variability in Chinese Patients with Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by selective impairment of upper and lower motor neurons. We aimed to investigate the genetic spectrum and variability in Chinese patients with ALS. A total of 24 familial ALS (FALS) and 21 early-onset sporadic ALS (SALS) of Chinese ancestry were enrolled. Targeted next-generation sequencing (NGS) was performed in the probands, followed by verification by Sanger sequencing and co-segregation analysis. Clinical features of patients with pathogenic or likely pathogenic variants were present. The mutation frequency of ALS-related genes was then analyzed in Chinese population. In this cohort, 17 known mutations (9 SOD1, 5 FUS, 2 TARDBP and one SETX) were identified in 14 FALS and 6 early-onset SALS. Moreover, 7 novel variants (SOD1 c.112G>C, OPTN c.811C>T, ERBB4 c.965T>A, DCTN1 c.1915C>T, NEFH c.2602G>A, NEK1 c.3622G>A, and TAF15 c.1535G>A) were identified. In southeastern Chinese FALS, the mutation frequency of SOD1, FUS, and TARDBP was 52.9%, 8.8%, 8.8% respectively. In early-onset SALS, FUS mutations were the most common (22.6%). In Chinese ALS cases, p.H47R is most frequent SOD1 mutations, while p.R521 is most common FUS mutation and p.M337V is most common TARDBP mutation. Our results revealed that mutations in SOD1, FUS and TARDBP are the most common cause of Chinese FALS, while FUS mutations are the most common cause of early-onset SALS. The genetic spectrum is different between Chinese ALS and Caucasian ALS.

Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited sensorimotor neuropathies. To clarify the genetic spectrum and clinical profiles in Chinese CMT patients, we enrolled 150 unrelated CMT patients from southeast China. We performed multiplex ligation-dependent probe amplification (MLPA) testing in all patients and next-generation sequencing (NGS) among those patients without PMP22 rearrangements. We identified PMP22 duplications in 40 patients and deletions in 12 patients. In addition, we found 19 novel variants and 36 known mutations in 57 patients. Among these 55 variants, 45 pathogenic or likely pathogenic variants were identified in 48 cases, and 10 variants with uncertain significance were identified in 9 cases. Therefore, we obtained a genetic diagnosis in 63.8% (88/138) of CMT patients and 66.7% (100/150) of all included patients. PMP22, GJB1, and MFN2 are the most common causative genes in CMT1 (demyelinated form), intermediate CMT, and CMT2 (axonal form), respectively. In this study, we identified a higher proportion of intermediate CMT, a relatively high frequency of NDRG1 mutations and clinical features of later onset age in CMT1A patients. Our results broaden the genetic and clinical spectrum of CMT patients, which can help optimize the genetic and clinical diagnosis.

Clinical features and genetic spectrum in Chinese patients with recessive hereditary spastic paraplegia.

BACKGROUND: Although many causative genes of hereditary spastic paraplegia (HSP) have been uncovered in recent years, there are still approximately 50% of HSP patients without genetically diagnosis, especially in autosomal recessive (AR) HSP patients. Rare studies have been performed to determine the genetic spectrum and clinical profiles of recessive HSP patients in the Chinese population. METHODS: In this study, we investigated 24 Chinese index AR/sporadic patients by targeted next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Further functional studies were performed to identify pathogenicity of those uncertain significance variants. RESULTS: We identified 11 mutations in HSP related genes including 7 novel mutations, including two (p.V1979_L1980delinsX, p.F2343 fs) in SPG11, two (p.T55 M, p.S308 T) in AP5Z1, one (p.S242 N) in ALDH18A1, one (p.D597fs) in GBA2, and one (p.Q486X) in ATP13A2 in 8 index patients and their family members. Mutations in ALDH18A1, AP5Z1, CAPN1 and ATP13A2 genes were firstly reported in the Chinese population. Furthermore, the clinical phenotypes of the patients carrying mutations were described in detail. The mutation (p.S242 N) in ALDH18A1 decreased enzyme activity of P5CS and mutations (p.T55 M, p.S308 T) in AP5Z1 induced lysosomal dysfunction. CONCLUSION: Our results expanded the genetic spectrum and clinical profiles of AR-HSP patients and further demonstrated the efficiency and reliability of targeted NGS diagnosing suspected HSP patients.

Identification and functional analysis of novel mutations in the SOD1 gene in Chinese patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective involvement of motor neurons in the central nervous system (CNS). The most common causative gene of ALS in the Chinese population is the Cu/Zn superoxide dismutase 1 (SOD1) gene, which accounts for 20-42.9% of familial ALS (FALS) and 1-2% of sporadic ALS (SALS) cases. In this study, we identify three novel SOD1 mutations, Gly17Cys, Pro75Ser, and His121Gln, in four ALS pedigrees. A functional analysis was performed, and the results showed that all three mutations could lead to the formation of misfolded proteins. In addition, genotype-phenotype correlations in these patients are also described. Our study helps to characterize the genotype and phenotype of ALS with SOD1 mutations.

A study about immunomodulatory effect and efficacy and prognosis of human umbilical cord mesenchymal stem cells in patients with chronic hepatitis B-induced decompensated liver cirrhosis.

BACKGROUND AND AIM: The aim of our study was to investigate the immunomodulatory effect and short-term efficacy and long-term prognosis of decompensated liver cirrhosis patients caused by hepatitis B after a double transplantation with human umbilical cord mesenchymal stem cells (hUCMSCs). METHODS: Fifty inpatients were recruited and given the same medical treatments, receiving hUCMSCs injection intravenously. Fifty-three patients (Group B) matched for age, sex, and baseline alanine aminotransferase, aspartate aminotransferase, albumin, total bilirubin, prothrombin time, and model for end-stage liver disease score and Child-Pugh classification, acted as the control group. RESULTS: Interleukin-6 and tumor necrosis factor alpha levels markedly decreased, and interleukin-10 level apparently increased in Group A at 2 and 4 weeks after treatment. Transforming growth factor beta in Group A increased more remarkably at 2 weeks after treatment. T4 cells and Treg cells in Group A were apparently higher than those in Group B at 2 and 4 weeks after treatment, and T8 cells and B cells were significantly lower than those in Group B. Aspartate aminotransferase levels in Group A were dramatically declining at 8 and 12 weeks after treatment. Levels of albumin, total bilirubin, and prothrombin time in Group A were apparently improved from 4 to 12 weeks after treatment. The improvements in model for end-stage liver disease and Child-Pugh scores in Group A were notably superior to those in Group B from 4 to 36 weeks after treatment. There were no remarkable differences in the incidence of developing liver failure throughout the follow-up period, but the mortality rate of Group A was lower than that of Group B. CONCLUSION: This therapeutic method may be an appropriate choice for patients with decompensated liver cirrhosis.

Subacute fulminant hepatic failure with intermittent fever.

BACKGROUND: Viral hepatitis B accounts for over 80% of acute hepatic failures in China and the patients die mainly of its complications. A patient with hepatic failure and fever is not uncommon, whereas repeated fever is rare. METHODS: A 32-year-old female was diagnosed with subacute hepatic failure and hepatitis B viral infection because of hyperbilirubinemia, coagulopathy, hepatic encephalopathy, serum anti-HBs-positive without hepatitis B vaccination, and typical intrahepatic pathological features of chronic hepatitis B. Plasma exchange was administered twice and she awoke with hyperbilirubinemia and discontinuous fever. RESULTS: Urethritis was confirmed and medication-induced fever and/or spontaneous bacterial peritonitis (Gram-negative bacillus infection) was suspected. The patient was treated with antibiotics, steroids and a Chinese herbal medicine, matrine, for three months and she recovered. CONCLUSION: The survival rate of patients with hepatic failure might be improved with comprehensive supporting measures and appropriate, timely management of complications.

[Lamivudine, interferon-alpha and oxymatrine treatment for the surviving hepatic failure patients with hepatitis B].

OBJECTIVE: To investigate the effect of lamivudine, interferon alpha and oxymatrine treatment for surviving hepatic failure patients with hepatitis B. METHODS: 200 hepatitis B patients, including 100 subacute or acute-on-chronic hepatic failure survivals (group A), and 100 chronic (group B, n=100) hepatic failure survivals, were enrolled in this study. Patients in group A received interferon alpha (n=35), lamivudine (n=33) , or combinational lamivudine and oxymatrine (n=32) therapy for six months; Patients in group B received lamivudine (n=49), or combinational lamivudine and oxymatrine (n=51) therapy for six months, respectively. After the treatment, all patients were followed-up for six months. RESULTS: At the end of follow-up, all patients in group A survived, while in group B three patients (6.1%) receiving lamivudine, and four (7.8%, P>0.05) receiving combinational therapy died; more than 90% of all survivals had their HBV DNA loss. The HBeAg/anti-HBe seroconversion rate in patients of group A treated with interferon alpha (9/17, 52.9%) was higher than that in patients treated with combinational lamivudine and matrine (5/16, 31.3%, P<0.05), which was higher than that in the patients treated with lamivudine alone (1/17, 5.9%, P<0.01), and the Knodell histological activity index score in patients treated with lamivudine (7.2+/-0.8, P<0.05) was lower than that in patients treated with interferon alpha (8.2+/-1.3, P<0.05), and the best efficacy was found in receiving combinational therapy (6.9+/-0.7, P<0.01); Lamivudine or lamivudine in combination with matrine significantly inhibited the intrahepatic inflammatory activities, but had no effect on the existing fibrosis in group B patients. CONCLUSION: Long term nucleotide analogues treatment may delay the progress of fibrosis in hepatitis B-induced hepatic failure survivals, and the administration of matrine in time may further enhance the anti-fibrotic effect of nucleotide analogues.

[Glycocorticosteroid administration prevents fulminant hepatic failure occurrence in patients with chronic hepatitis B of severe degree].

OBJECTIVE: To prevent chronic severe hepatitis, even more fulminant hepatic failure (FHF) occurrence in patients with chronic hepatitis B of severe degree using steroid. METHODS: 120 patients were randomized into conventional supporting treatment and steroid treatment groups. The latter, 62 patients were given intravenously hydrocortisone sodium succinate at the dose of 150 mg to approximately 200 mg everyday plus support care. RESULTS: The rate of deteriorating to chronic severe hepatitis in steroid treatment group was significantly lower than that of conventional group (22% vs 48%, x(2) =7.60, P<0.01). 53.6% (15/28) patients with chronic severe hepatitis in conventional group died, while only 28.6% (4/14) in steroid treatment group succumbed to terminal liver disease (x(2)=0.02, P>0.05). There was no difference between the two groups regarding to complications incidence: gastrointestinal bleeding and infections except for some controllable serious reverse events, such as candidiasis, diabetes, herpes zoster and pulmonary tuberculosis found in some patients in steroid-treated group. CONCLUSION: These results suggest that steroid administration with improved support care not only is likely to prevent chronic severe hepatitis occurrence in patients with chronic viral hepatitis of severe degree, but also shows some efficacy for FHF, which warrant further investigation.