Comparative effectiveness and safety of intravenous methylprednisolone and tacrolimus monotherapy in ocular myasthenia gravis with unsatisfactory prednisone responses: a retrospective study.

BACKGROUND: Oral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy. METHODS: We retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded. RESULTS: Both IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p = 0.002; 69.0% (20/29) vs 40.0% (10/25), p = 0.033; 69.0% (20/29) vs 46.4% (13/28), p = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066-2.975; p = 0.028). All the adverse events were transient and tolerable. CONCLUSION: Our findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.

A TGF-ß signaling-related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response.

AIMS: The dysregulation of TGF-ß signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-ß signaling in glioma is currently unclear. METHODS: Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. RESULTS: In glioma, a TGF-ß signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-ß signaling pathway. CONCLUSIONS: A prognostic lncRNA signature of TGF-ß signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression.

Facial emotion recognition and alexithymia in Chinese male patients with deficit schizophrenia.

Deficit schizophrenia (DS) has been proposed as a pathophysiologically distinct schizophrenia subtype. This study investigated facial emotion recognition deficits and alexithymia in DS and non-deficit schizophrenia patients (NDS) and their relationships with other clinical variables. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Scale for the Assessment of Positive Symptoms (SAPS) were employed to evaluate the psychiatric symptoms in patients with schizophrenia. Facial emotion recognition deficits and Alexithymia were assessed in DS, NDS, and control groups by The Chinese Facial Emotion Test (CFET) and the Toronto Alexithymia Scale-20 (TAS-20). Compared with control group, both DS and NDS patients exhibited more severe facial emotion recognition impairments, with the exception of "happy faces" in NDS patients, as well as higher alexithymia scores. In DS patients, correct frequency for fear recognition and total CFET score were negatively correlated with TAS-20 Factor 3 subscore for "externally oriented thinking". Total TAS-20 score was positively correlated with BPRS negative symptom and SANS score in DS patients. In contrast, there were no correlations between TAS-20 scores/subscores and psychiatric symptoms in NDS patients. These findings indicated distinct facial emotion recognition impairments in DS and NDS patients. Alexithymia might be specifically related to the negative symptom in DS patients, suggesting DS as a unique schizophrenic subtype.

[Metabolic characteristics of air microbial communities from sandstorm source areas of the Taklamakan desert].

The aim was to compare the characteristics and the differences in carbon catabolic diversity of air samples collected from five locations that around the edge of Taklamakan desert. The characteristics and the differences of carbon metabolic profiles were detected by using the BIOLOG micro plate (BIOLOG EcoPlate). The results showed that the average well color development (AWCD) curve of all five samples did not reach clear saturation during the incubation time (10 days), but differences among them were significant. The highest AWCD value appeared in Shache and the lowest was in Hotan, which were 0.24 and 0.1, respectively. Carbon utilization showed that all samples exhibited high level of polymer, carbohydrates, amino acids and carboxylic acid; however, amine and the phenol compound were the lowest. Principal components analysis (PCA) indicated that twenty categories of carbon significantly related to PC1 and twelve categories for PC2. Hierarchical cluster analysis showed these five areas could be divided into 2 clusters: (1) Hotan, Pishan, (2) Shache, Luntai, Ulugqat. Canonical correspondence analysis (CCA) showed that those community functional diversities were highly affected by some environmental factors, such as wind speed, altitude, humidity. Further investigation by correlation analysis revealed that the microbial communities using single carbon source were significantly affected by abiotic factors, such as the utilization of beta-methyl-D-glucoside, D-galacturonic acid and putrescine had significantly positive correlation (P < 0.05) with latitude; 2-hydroxy benzoic acid and alpha-D-lactose significantly related to wind speed (P < 0.05); and D-glucosaminic acid was positive with air pressure, but it negatively correlated with altitude (P < 0.05). In conclusion,the carbon sources provided by BIOLOG EcoPlate were utilized slowly by air microbial communities; and the characteristics of the air community carbon catabolic along the edge of the Taklamakan desert revealed regional feature, which may be affected by environmental factors.

[Congenital myopathy with type 1 fiber predominance in two children].

Non-progressive congenital myopathy is a group of muscle diseases occurring at birth or during teenage years. A number of new reports of congenital myopathy, such as homogeneous bodies myopathy, muscle quality control myopathy and type 1 fiber predominance have recently been reported, but they lack of sufficient quantity and constant clinico-pathologic manifestations. This paper reports two cases of congenital myopathy with type 1 fiber predominance confirmed by muscle biopsy. The clinical manifestations of the two children (a 4.5-year-old girl and an 11-year-old boy) included non-progressive symptoms of muscle weakness, skeletal deformities and other clinical features of congenital myopathy. The physical examinations showed a long face or figure and funnel chest or kyphosis/scoliosis, high palatal arch and wing-like shoulder. Serum levels of creatine kinase were normal but slightly elevated serum lactate dehydrogenase levels were noted in the two children. The skeletal muscle biopsy by ATPase staining showed that type 1 fibers accounted for more than 90% of the total number of muscle fibers. No other abnormal pathological changes, such as central cores, muscle tube and central nuclei, were found in the two children.

[SMAD4 gene polymorphisms and genetic susceptibility of coal work's pneumoconiosis].

OBJECTIVE: to explore whether 6 tagging single nucleotide polymorphisms (SNPs) within SMAD4 gene were involved in the genetic susceptibility of coal worker's pneumoconiosis (CWP) by case-control study. METHODS: this study consisted of 438 CWP patients and 448 controls. All study subjects were Han Chinese, underground coal miners and recruited from coal mines of Xuzhou Mining Business Group Co Ltd. The 5 ml venous blood sample was obtained from all studied subjects and extracted genome DNA from the isolated leucocytes. Six SNPs were selected from the HapMap and detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: the single SNP analyses showed that the genotype frequencies of SMAD4 (rs10502913) was significantly different from those in controls (P < 0.05). Multivariate logistic regression analyses revealed that SMAD4 (rs10502913) AA genotype was associated with increased risk of CWP (adjusted OR = 1.63, 95%CI = 1.00 - 2.69, P = 0.05) and this was evident among subgroups of those smoker (adjusted OR = 2.28, 95%CI = 1.09 ∼ 4.80, P < 0.05) and cases with stage I (adjusted OR = 2.42, 95%CI = 1.41 ∼ 4.14, P < 0.01). The SMAD4 (rs9304407) GG genotype was associated with an decreased risk of CWP (adjusted OR = 0.65, 95%CI = 0.43 ∼ 0.98, P < 0.05) and the further stratification analysis showed that the risk of CWP was decreased in nonsmoking groups. CONCLUSIONS: our results suggest that individuals with the SMAD4 (rs10502913) AA genotype was associated with an increased risk of CWP. However, carriers of SMAD4 (rs9304407) GG genotype have a protective effect on the developing CWP.