Missense mutation of c.635 T > C in CAPN3 impairs muscle injury repair in a Limb-Girdel Muscular Dystropy Model.

Limb-girdle muscular dystrophy recessive 1 (LGMDR1), previously known as LGMD2A, is a specific LGMD caused by a gene mutation encoding the calcium-dependent neutral cysteine protease calpain-3 (CAPN3). In our study, the compound heterozygosity with two missense variants c.635 T > C (p.Leu212Pro) and c.2120A > G (p.Asp707Gly) was identified in patients with LGMDR1. However, the pathogenicity of c.635 T > C has not been investigated. To evaluate the effects of this novel likely pathogenic variant to the motor system, the mouse model with c.635 T > C variant was prepared by CRISPR/Cas9 gene editing technique. The pathological results revealed that a limited number of inflammatory cells infiltrated the endomyocytes of certain c.635 T > C homozygous mice at 10 months of age. Compared with wild-type mice, motor function was not significantly impaired in Capn3 c. 635 T > C homozygous mice. Western blot and immunofluorescence assays further indicated that the expression levels of the Capn3 protein in muscle tissues of homozygous mice were similar to those of wild-type mice. However, the arrangement and ultrastructural alterations of the mitochondria in the muscular tissues of homozygous mice were confirmed by electron microscopy. Subsequently, muscle regeneration of LGMDR1 was simulated using cardiotoxin (CTX) to induce muscle necrosis and regeneration to trigger the injury modification process. The repair of the homozygous mice was significantly worse than that of the control mice at day 15 and day 21 following treatment, the c.635 T > C variant of Capn3 exhibited a significant effect on muscle regeneration of homozygous mice and induced mitochondrial damage. RNA-sequencing results demonstrated that the expression levels of the mitochondrial-related functional genes were significantly downregulated in the mutant mice. Taken together, the results of the present study strongly suggested that the LGMDR1 mouse model with a novel c.635 T > C variant in the Capn3 gene was significantly dysfunctional in muscle injury repair via impairment of the mitochondrial function.

[Genetic diversity and population structure of germplasm resources of Amomum villosum based on SSR markers].

Amomum villosum, serving as an important medicinal material, is complex in the genetic background of germplasm resources. Exploring the genetic diversity and genetic relationship of germplasm resources is conducive to clarifying the germplasm source and genetic background of A. villosum, so as to improve the efficiency of parent selection and variety breeding of A. villosum. Seventy-one pairs of SSR primers were used for PCR amplification of 84 A. villosum samples by polyacrylamide gel electrophoresis. Fifty-four pairs of SSR primers with high polymorphism were screened out for the analysis of genetic diversity. The results showed that 293 alleles were detected from 84 germplasm resources by 54 pairs of SSR primers, with an average of 5.32 alleles for each pair of primers, and a variation range of 3-8, and the primer AVL12 marked the highest number of alleles. The PIC value of each locus varied from 0.068 7 to 0.828 9, with an average of 0.529 9, and the highest was marked by AVL24. The genetic diversity of A. villosum was the highest in Yunnan, followed by Guangxi, and the lowest was found in Guangdong. The population structure analysis and cluster analysis showed that the samples were classified into two groups. In terms of origin, samples from Yunnan and Guangxi had a close genetic relationship, and there was no obvious differentiation of A, villosum resources from different origins. In this study, 54 pairs of SSR markers were used to analyze the genetic diversity and population structure of 84 germplasm resources, which can reflect the genetic relationship between A. villosum samples from different germplasm sources and different populations, thus providing a theoretical basis for the collection, research, and breeding of A. villosum resources.

[Male infertility - related gene knockout mouse models].

The pathogenesis of male infertility is rather complicated. The establishment of animal models, especially mouse models, of male infertility, provides a model basis for the studies of the roles and molecular mechanisms of infertility-related genes. Currently there are mainly three types of mouse models for biomedical researches, namely, the mouse model made by the knockout, knock-in or gene capture method, transgenic mouse model, and chemically induced point mutant mouse model. This review summarizes male infertility - related gene knockout mouse models, aiming to find a suitable animal model for studying the pathogenesis of male infertility.

Trace Elements in the Feathers of Waterfowl from Nanhaizi Wetland, Baotou, China.

The trace element concentrations (Cr, Ni, Pb, Hg, Cu, Zn, Mn, and Fe) of feathers from Ferruginous duck (Aythya nyroca), Gadwall (Anas strepera), and Green-winged Teal (Anas crecca) from Nanhaizi Wetland, China were measured. (1) There were significant differences in the concentrations of the Cr, Ni, and Pb among the waterfowl species. The concentrations of Cr and Ni in Gadwall feathers and Pb in Green-winged Teal feathers were higher than the concentrations of Cr, Ni and Pb in Ferruginous duck. (2) The Pb concentrations in the feathers of four Green-winged Teals and one Ferruginous duck, Cr concentrations in the feathers of Gadwalls (geomean 5.33 µg g-1 dry weight) and Green-winged Teals (geomean 4.55 µg g-1 dry weight) exceeded the thresholds at which they pose a threat to bird health (i.e., Pb > 4 µg g-1, Cr > 2.8 µg g-1). (3) The Cu, Zn, Fe, and Mn concentrations of feathers were within the normal ranges reported for most waterfowl.

Brief cognitive-behavioural therapy for patients in the community with schizophrenia: randomised controlled trial in Beijing, China.

BackgroundBrief cognitive-behavioural therapy (CBT) is an emerging treatment for schizophrenia in community settings; however, further trials are needed, especially in non-Western countries.AimsTo test the effects of brief CBT for Chinese patients with schizophrenia in the community (trial registration: ChiCTR-TRC-13003709).MethodA total of 220 patients with schizophrenia from four districts of Beijing were randomly assigned to either brief CBT plus treatment as usual (TAU) or TAU alone. Patients were assessed at baseline, post-treatment and at 6- and 12-month follow-ups by raters masked to group allocation.ResultsAt the post-treatment assessment and the 12-month follow-up, patients who received brief CBT showed greater improvement in overall symptoms, general psychopathology, insight and social functioning. In total, 37.3% of those in the brief CBT plus TAU group experienced a clinically significant response, compared with only 19.1% of those in the TAU alone group (P = 0.003).ConclusionsBrief CBT has a positive effect on Chinese patients with schizophrenia in the community.

Generation of an induced pluripotent stem cell line (CSBZZUi001-A) from a female Alzheimer's patient carrying the PSEN1 709 T > C heterozygous mutation.

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

Dyssynchronous ventricular contraction in Wolff-Parkinson-White syndrome: a risk factor for the development of dilated cardiomyopathy.

UNLABELLED: Emerging evidence suggests that significant left ventricular dysfunction may arise in right-sided septal or paraseptal accessory pathways (APs) with Wolff-Parkinson-White syndrome, even in the absence of recurrent or incessant tachycardia. During 1 year and 9 months, we identified four consecutive female children with median age of 8 years diagnosed as having dilated cardiomyopathy (DCM) combined with overt right-sided APs several years ago. Incessant or recurrent tachycardia as the cause of DCM could be excluded. Anti-heart failure chemotherapy did not produce satisfactory effects. The patients underwent radiofrequency ablations (RFCAs). This report describes the clinical and echocardiographic characteristics of the cases before and after the ablation. Dyssynchronous ventricular contraction was observed in all patients. The locations of the APs were the right-sided anteroseptum and the free wall (n = 2 each). All patients received successful RFCAs. Their physical activities and growth improved greatly, and the echocardiographic data demonstrated that their left ventricular (LV) contraction recovered to synchrony shortly after the ablation and that their LV function recovered to normal gradually during the follow-up. CONCLUSIONS: A causal relationship between overt ventricular preexcitation and the development of DCM is supported by the complete recovery of LV function and reversed LV remodeling after the loss of ventricular preexcitation. Preexcitation-related dyssynchrony was probably the crucial mechanism. Not only right-sided septal or paraseptal but also free wall overt APs may induce LV dysfunction and even DCM. AP-induced DCM is an indication for ablation with a good prognosis.

Suicide attempt and suicidal ideation and their associations with demographic and clinical correlates and quality of life in Chinese schizophrenia patients.

OBJECTIVES: This study aimed to examine the prevalence and correlates of lifetime suicide attempts and current suicidal ideation in community-dwelling schizophrenia patients in China. METHOD: A sample of 540 schizophrenia patients was randomly selected in Beijing, China. All subjects were interviewed using standardized assessment instruments and their basic socio-demographic and clinical data including history of suicide attempts were collected. RESULTS: The prevalence of lifetime suicide attempts and the point prevalence of suicidal ideation were 12.0%, and 21.1%, respectively. In multiple logistic regression analyses, the presence of lifetime suicide attempt was independently associated with rural residence, having major medical conditions and better social functioning, while higher likelihood of current suicidal ideation was associated with past suicide attempt, the severity of overall psychopathology and depressive symptoms and lower psychological quality of life (QOL). CONCLUSION: Among Chinese outpatients with schizophrenia, increased current symptoms and poorer QOL were correlated with current suicidal ideation, while demographic factors and indicators of greater social support were mostly correlated with lifetime suicide attempts. This study may help to identify important subgroups of patients with schizophrenia at particularly high risk of suicidal behavior.

Tracking Research on Hemoglobin-Based Oxygen Carriers: A Scientometric Analysis and In-Depth Review.

Numerous studies on the formulation and clinical applications of novel hemoglobin-based oxygen carriers (HBOCs) are reported in the scientific literature. However, there are fewer scientometric analysis related to HBOCs. Here, we illustrate recent studies on HBOCs using both a scientometric analysis approach and a scope review method. We used the former to investigate research on HBOCs from 1991 to 2022, exploring the current hotspots and research trends, and then we comprehensively analyzed the relationship between concepts based on the keyword analysis. The evolution of research fields, knowledge structures, and research topics in which HBOCs located are revealed by scientometric analysis. The elucidation of type, acting mechanism, potential clinical practice, and adverse effects of HBOCs helps to clarify the prospects of this biological agent. Scientometrics analyzed 1034 publications in this research field, and these findings provide a promising roadmap for further study.

Quality of life in community-dwelling patients with schizophrenia in China.

The aim of this study was to assess Chinese schizophrenia patients' quality of life (QOL) and identify its demographic and clinical correlates. A random sample of 540 community-dwelling schizophrenia patients was interviewed using standardized assessment instruments. The patients' basic sociodemographic and clinical data and QOL were collected. Compared with the general population, patients had significantly lower scores in the physical and psychological QOL domains. Multivariate analyses showed that better social support independently predicted higher QOL in all domains, whereas more severe positive symptoms predicted worse psychological and environmental domains. Overall psychopathology predicted both worse physical and psychological domains; depressive symptoms and being married predicted worse physical and social QOL, respectively. Our results suggest that therapeutic and psychosocial interventions alleviating positive and depressive symptoms and improving poor social support and marriage-related problems in Chinese patients with schizophrenia might be of considerable benefit in improving their QOL.

[Localization diagnosis of laparoscopic ultrasonograph in laparoscopic surgery of insulinoma].

OBJECTIVE: To discuss the localization diagnosis value of laparoscopic ultrasonography in laparoscopic surgery of insulinoma. METHODS: Retrospectively reviewed the results of laparoscopic ultrasonography in 32 patients from Jan 2007 to Aug 2008 with insulinoma which confirmed after surgery, and analyzed the detection rate of laparoscopic ultrasonography. RESULTS: Insulinoma tumors were success located in 31 patients among 32 patients by laparoscopic ultrasonography. The detection rate was 96.9% and the location accurate rate was 100%. Thirty-seven insulinoma tumors were detected in 31 cases, including 29 solitary insulinoma and 2 multiple insulinomas. One patient did not show a definite tumor in the pancreas and extrapancreatic organ during the laparoscopic ultrasonography examination. CONCLUSION: Laparoscopic ultrasonography has a high detection rate in localizing diagnosis of insulinoma and can clear display the relationship between tumor and adjacent tissue. It is useful for surgeon to select the suitable operation modality.

High-throughput liquid chromatography mass-spectrometry-driven lipidomics discover metabolic biomarkers and pathways as promising targets to reveal the therapeutic effects of the Shenqi pill.

Lipidomics, a branch of metabonomics, could provide a powerful technique for discovery of lipid molecules to reveal disease status and drug efficacy. The Shenqi pill (SQP) is a representative prescription for clinical application in the prevention and treatment of kidney-yang deficiency syndrome (KYDS). However, its effect mechanism is still not clear. This article aims to reveal the intervention effect of SQP on KYDS from the perspective of lipid metabolism. In this study, SQP was used to intervene in the rat model of KYDS, on the foundation of successfully replicating the rat model of KYDS induced by corticosterone. The MetaboAnalyst tool was used for analysis of the serum metabolic profile and pattern recognition of KYDS model, based on UPLC-SYNAPT-G2-Si-HDMS. Finally, twenty-two potential lipid biomarkers related to the KYDS model were characterized, and the effects of SQP on regulating potential lipid markers in serum of KYDS model were analyzed. There were 10 biomarkers and seven metabolic pathways closely related to SQP therapy for KYDS were found. The action mechanism and targets of SQP in treating KYDS were explored based on high-throughput lipidomics. This work could provide valuable data and scientific evidence in subsequent studies for the treatment of KYDS.

Selection of scFvs specific for the HepG2 cell line using ribosome display.

The aim of this study was to construct a ribosome display library of single chain variable fragments (scFvs) associated with hepatocarcinoma and screen such a library for hepatocarcinoma-binding scFvs. mRNA was isolated from the spleens of mice immunized with hepatocellular carcinoma cell line HepG2. Heavy and k chain genes (VH and k) were amplified separately by RT-PCR, and an anti-HepG2 VH/k chain ribosome display library was constructed by assembling VH and k into the VH/k chain with a specially constructed linker by SOE-PCR. The VH/k chain library was transcribed and translated in vitro using a rabbit reticulocyte lysate system. In order to isolate specific scFvs, recognizing HepG2 negative selection on a normal hepatocyte line WRL-68 was carried out before three rounds of positive selection on HepG2. After three rounds of panning, cell enzyme-linked immunosorbent assay (ELISA) showed that one of the scFvs had high affinity for the HepG2 cell and lower affinity for the WRL-68 cell. In this study, we successfully constructed a native ribosome display library. Such a library would prove useful for direct intact cell panning using ribosome display technology. The selected scFv had a potential value for hepatocarcinoma treatment.

[Role of contrast-enhanced ultrasound in management of splenic trauma].

OBJECTIVE: To study the role of contrast-enhanced ultrasound (CEUS) in the management of splenic trauma METHODS: Forty patients with splenic trauma underwent CEUS examination and then different management were provided according to the examination results and the general status of patients: conservative treatment (group I, n = 19); CEUS-guided injective therapy (group II, n = 6); and surgery (group III, n = 15). RESULTS: Eighteen patients were cured in group I and one patient experienced rehaemorrhagia. The haemostatic effect of CEUS-guided injective therapy was obvious in all six patients in group II. Among them, one patient experienced arteriovenous fistula, which was resolved after one week of injective therapy. Fifteen patients in Group III underwent surgery and were cured. CONCLUSION: CEUS can provide reliable information for therapy mode selection in patients with splenic trauma and can be used to guide injective therapy.

Grey matter reduction in the caudate nucleus in patients with persistent negative symptoms: An ALE meta-analysis.

OBJECTIVES: In the present study, we used Activation Likelihood Estimation (ALE) meta-analysis to quantitatively examine brain grey matter reduction in schizophrenia patients with persistent negative symptoms (PNS). METHOD: A total of 12 voxel-based morphometry (VBM) studies were included in ALE meta-analysis using more stringent criterion of PNS. RESULTS: Significant grey matter reduction in the PNS group relative to controls was observed in the left caudate nucleus, the left precentral region, the left middle frontal region, the bilateral parahippocampal region, the left anterior cingulate region, the bilateral medial frontal gyrus, the thalamus and the insula. CONCLUSION: Our results suggest that brain regions in the reward network may be specifically related to PNS, especially the left caudate nucleus. It is possible that abnormality in reward processing may constitute the neural basis of PNS.

Prospection deficits in schizophrenia: Evidence from clinical and subclinical samples.

Previous research has revealed anticipatory pleasure deficits in people with schizophrenia and people with social anhedonia but who do not have schizophrenia. Prospection is an important component of anticipatory pleasure, but little is known about the role of prospection in social anhedonia. In 2 studies, we investigated prospection and anticipatory pleasure in people with schizophrenia and people with social anhedonia using an affective prospection task and a self-report measure, the Temporal Experience of Pleasure Scale (TEPS). In Study 1, we found that people with schizophrenia (n = 31) reported less TEPS anticipatory pleasure, generated less rich and vivid prospections, and reported less preexperiencing of future events than people without schizophrenia (n = 29). In Study 2, we found that people with social anhedonia (n = 34) reported less TEPS anticipatory pleasure, generated less rich prospections, and reported less pleasure and preexperiencing for future events than people without social anhedonia (n = 33). Taken together, prospection impairments and decreased anticipatory pleasure were observed in schizophrenia and social anhedonia. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Revisiting the persistent negative symptoms proxy score using the Clinical Assessment Interview for Negative Symptoms.

OBJECTIVE: The present study aimed to validate a severity cut-off of negative symptoms for persistent negative symptoms (PNS) identification using the Clinical Assessment Interview for Negative Symptoms (CAINS). METHOD: A total of 206 patients with schizophrenia were recruited and divided into the PNS group (n = 57) and the Non-PNS group (n = 149) using PNS criteria based on the SANS and the SAPS. To determine the appropriate cut-offs on the CAINS in identifying PNS, Receiver Operating Characteristic (ROC) curve analysis was conducted in the PNS and Non-PNS groups. RESULTS: Our results showed that the cutoffs for identifying PNS on the CAINS total score, the Motivation and Pleasure (MAP) subscale score and the Expression (EXP) subscale score were 25, 17, and 5 respectively. Area Under the Curve (AUC) analysis indicated excellent discrimination of the PNS group from the Non-PNS group using the cut-off for the CAINS total score. However, discrimination was somewhat better for the MAP subscale score than the EXP subscale score. The Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the MAP subscale were 81.54% and 97.16%. CONCLUSION: We found that the cut-off scores derived from the CAINS to identify PNS are comparable to existing scales. The CAINS offers an alternative means in identifying PNS patients in clinical trials that overcomes methodological and conceptual limitations of older scales.

Cross Cultural Validation and Extension of the Clinical Assessment Interview for Negative Symptoms (CAINS) in the Chinese Context: Evidence from a Spectrum Perspective.

The Clinical Assessment Interview for Negative Symptoms (CAINS) was designed in accordance with the recent theory and research in social affective neuroscience and to address the psychometric and conceptual limitations of other instruments assessing negative symptoms. The present study aimed to provide a large-scale validation of the CAINS in China and examine its applicability and validity evidence across the schizophrenia spectrum. Using confirmatory factor analysis, our results replicated the original findings in the US development samples that the CAINS possesses a stable 2-factor structure, namely "motivation/pleasure" and "expression". We also found significant correlations between the CAINS and other negative symptom measures. The CAINS demonstrated good discriminant validity in differentiating negative symptoms in people with schizophrenia, nonpsychotic first-degree relatives and people with social anhedonia. People with schizophrenia exhibited significantly higher CAINS subscale scores than first-degree relatives and healthy controls. In addition, first-degree relatives had higher "motivation/pleasure" scores than healthy controls. The "motivation/pleasure" subscale scores of individuals with social anhedonia were also significantly higher than healthy controls.