The characteristic and biomarker value of transcranial sonography in cerebellar ataxia.

OBJECTIVE: Transcranial sonography (TCS) is a noninvasive neuroimaging technique, visualizing deep brain structures and the ventricular system. Although widely employed in diagnosing various movement disorders, such as Parkinson's disease and dystonia, by detecting disease-specific abnormalities, the specific characteristics of the TCS in cerebellar ataxia remain inconclusive. We aimed to assess the potential value of TCS in patients with cerebellar ataxias for disease diagnosis and severity assessment. METHODS: TCS on patients with genetic and acquired cerebellar ataxia, including 94 with spinocerebellar ataxias (SCAs) containing 10 asymptomatic carriers, 95 with cerebellar subtype of multiple system atrophy (MSA-C), and 100 healthy controls (HC), was conducted. Assessments included third ventricle width, substantia nigra (SN) and lentiform nucleus (LN) echogenicity, along with comprehensive clinical evaluations and genetic testing. RESULTS: The study revealed significant TCS abnormalities in patients with cerebellar ataxia, such as enlarged third ventricle widths and elevated rates of hyperechogenic SN and LN. TCS showed high accuracy in distinguishing patients with SCA or MSA-C from HC, with an AUC of 0.870 and 0.931, respectively. TCS abnormalities aided in identifying asymptomatic SCA carriers, effectively differentiating them from HC, with an AUC of 0.725. Furthermore, third ventricle width was significantly correlated with SARA and ICARS scores in patients with SCA3 and SCOPA-AUT scores in patients with MSA-C. The SN area and SARA or ICARS scores in patients with SCA3 were also positively correlated. INTERPRETATION: Our findings illustrate remarkable TCS abnormalities in patients with cerebellar ataxia, serving as potential biomarkers for clinical diagnosis and progression assessment.

Recombinant fibroblast growth factor 4 ameliorates axonal regeneration and functional recovery in acute spinal cord injury through altering microglia/macrophage phenotype.

Neuroinflammation is one of the extensive secondary injury processes that aggravate metabolic and cellular dysfunction and tissue loss following spinal cord injury (SCI). Thus, an anti-inflammatory strategy is crucial for modulating structural and functional restoration during the stage of acute and chronic SCI. Recombinant fibroblast growth factor 4 (rFGF4) has eliminated its mitogenic activity and demonstrated a metabolic regulator for alleviating hyperglycemia in type 2 diabetes and liver injury in non-alcoholic steatohepatitis. However, it remains to be explored whether or not rFGF4 has a neuroprotective effect for restoring neurological disorders, such as SCI. Here, we identified that rFGF4 could polarize microglia/macrophages into the restorative M2 subtype, thus exerting an anti-inflammatory effect to promote neurological functional recovery and nerve fiber regeneration after SCI. Importantly, these effects by rFGF4 were related to triggering PI3K/AKT/GSK3ß and attenuating TLR4/NF-κB signaling axes. Conversely, gene silencing of the PI3K/AKT/GSK3ß signaling or pharmacological reactivation of the TLR4/NF-κB axis aggravated inflammatory reaction. Thus, our findings highlight rFGF4 as a potentially therapeutic regulator for repairing SCI, and its outstanding effect is associated with regulating macrophage/microglial polarization.

[Retracted] MicroRNA­15a­5p­targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 3A and B on p. 1306 were strikingly similar to data appearing in different form in a paper by different authors at a different research institute that had already been submitted for publication. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 46: 1301­1310, 2020; DOI: 10.3892/ijmm.2020.4704].

Peripheral Inflammatory and Immune Landscape in Multiple System Atrophy: A Cross-Sectional Study.

BACKGROUND: Neuroinflammation might contribute to the pathogenesis of multiple systemic atrophy (MSA). However, specific alterations in the peripheral inflammatory and immune profiles of patients with MSA remain unclear. OBJECTIVES: To determine the peripheral inflammatory and immune profiles of patients with MSA and their potential value as biomarkers for facilitating clinical diagnosis and monitoring disease severity. METHODS: This cross-sectional study included 235, 240, and 235 patients with MSA, patients with Parkinson's disease (PD), and healthy controls (HCs), respectively. Inflammatory and immune parameters were measured in peripheral blood, differences between groups were assessed, and clusters were analyzed. Associations between the parameters and clinical characteristics of MSA were assessed using Spearman and partial correlation analyses. RESULTS: Significant differences were observed especially in monocytes, neutrophils-to-lymphocyte ratio (NLR) and neutrophils-to-lymphocyte ratio (MPV) between MSA patients and HCs (P < 0.01). Monocytes and uric acid (UA) levels were also significantly different between the MSA and PD patients (P < 0.05). The combination of NLR and MPV distinguished MSA-P patients from HCs (areas under the curve = 0.824). In addition, complement components C4 and C3 were significantly correlated with the Scale Outcomes in PD for Autonomic Symptoms and Wexner scale, whereas immunoglobulin G (IgG) was significantly correlated with scores of Unified Multiple System Atrophy Rating Scale (P < 0.05). CONCLUSIONS: In MSA patients, monocytes, NLR and MPV might serve as potential diagnostic biomarkers, whereas MLR, C3, C4, and IgG significantly correlate with disease severity. © 2023 International Parkinson and Movement Disorder Society.

No Correlation between Plasma GPNMB Levels and Multiple System Atrophy in Chinese Cohorts.

BACKGROUND: Glycoprotein nonmetastatic melanoma protein B (GPNMB) has been demonstrated to mediate pathogenicity in Parkinson's disease (PD) through interactions with α-synuclein, and plasma GPNMB tended to be a novel biomarker for PD. OBJECTIVE: The goal of this study was to investigate whether plasma GPNMB could act as a potential biomarker for the clinical diagnosis and severity monitoring of multiple system atrophy (MSA), another typical synucleinopathy. METHODS: Plasma GPNMB levels in patients with MSA, patients with PD, and healthy control subjects (HCs) were quantified using enzyme-linked immunosorbent assays. RESULTS: A total of 204 patients with MSA, 65 patients with PD, and 207 HCs were enrolled. The plasma GPNMB levels in patients with MSA were similar to those in HCs (P = 0.251) but were significantly lower than those in patients with PD (P = 0.003). Moreover, there was no significant correlation detected between the plasma GPNMB levels and disease severity scores of patients with MSA. CONCLUSIONS: No evidence was detected for the biomarker potential of plasma GPNMB in MSA. © 2023 International Parkinson and Movement Disorder Society.

Diagnostic and prognostic performance of plasma neurofilament light chain in multiple system atrophy: a cross-sectional and longitudinal study.

BACKGROUND: The longitudinal dynamics of neurofilament light chain (NfL) in multiple system atrophy (MSA) were incompletely illuminated. This study aimed to explore whether the plasma NfL (pNfL) could serve as a potential biomarker of clinical diagnosis and disease progression for MSA. METHODS: We quantified pNfL concentrations in both a large cross-sectional cohort with 214 MSA individuals, 65 PD individuals, and 211 healthy controls (HC), and a longitudinal cohort of 84 MSA patients. Propensity score matching (PSM) was used to balance the age between the three groups. The pNfL levels between groups were compared using Kruskal-Wallis test. Linear mixed models were performed to explore the disease progression-associated factors in longitudinal MSA cohort. Random forest model as a complement to linear models was employed to quantify the importance of predictors. RESULTS: Before and after matching the age by PSM, the pNfL levels could reliably differentiate MSA from HC and PD groups, but only had mild potential to distinguish PD from HC. By combining linear and nonlinear models, we demonstrated that pNfL levels at baseline, rather than the change rate of pNfL, displayed potential prognostic value for progression of MSA. The combination of baseline pNfL levels and other modifiers, such as subtypes, Hoehn-Yahr stage at baseline, was first shown to improve the diagnosis accuracy. CONCLUSIONS: Our study contributed to a better understanding of longitudinal dynamics of pNfL in MSA, and validated the values of pNfL as a non-invasive sensitive biomarker for the diagnosis and progression. The combination of pNfL and other factors is recommended for better monitoring and prediction of MSA progression.

Coffin-Siris syndrome in two chinese patients with novel pathogenic variants of ARID1A and SMARCA4.

BACKGROUND: Coffin-Siris syndrome (CSS) is a rare congenital syndrome characterized by developmental delay, intellectual disability, microcephaly, coarse face and hypoplastic nail of the fifth digits. Heterozygous variants of different BAF complex-related genes were reported to cause CSS, including ARID1A and SMARCA4. So far, no CSS patients with ARID1A and SMARCA4 variants have been reported in China. OBJECTIVE: The aim of the current study was to identify the causes of two Chinese patients with congenital growth deficiency and intellectual disability. METHODS: Genomic DNA was extracted from the peripheral venous blood of patients and their family members. Genetic analysis included whole-exome and Sanger sequencing. Pathogenicity assessments of variants were performed according to the guideline of the American College of Medical Genetics and Genomics. The phenotypic characteristics of all CSS subtypes were summarized through literature review. RESULTS: We identified two Chinese CSS patients carrying novel variants of ARID1A and SMARCA4 respectively. The cases presented most core symptoms of CSS except for the digits involvement. Additionally, we performed a review of the phenotypic characteristics in CSS, highlighting phenotypic varieties and related potential causes. CONCLUSIONS: We reported the first Chinese CSS2 and CSS4 patients with novel variants of ARID1A and SMARCA4. Our study expanded the genetic and phenotypic spectrum of CSS, providing a comprehensive overview of genotype-phenotype correlations of CSS.

Serum vitamin levels in multiple system atrophy: A case-control study.

Aim: There is increasing evidence suggesting that vitamins may play important roles in the pathogenesis of multiple system atrophy (MSA). The purpose of this study was to detect the changes of serum vitamin levels and investigate their correlation with disease severity in MSA patients. Methods: In this cross-sectional study, 244 MSA patients, 200 Parkinson's disease (PD) patients and 244 age-gender matched healthy controls were recruited. Serum vitamin levels were measured, including vitamin A, B1, B2, B9 (folate), B12, C, D, and E. Relevant clinical scales were used to assess the disease severity of MSA patients. Results: Compared with the healthy controls, decreased serum folate levels and increased serum vitamin A and C levels were detected in MSA patients. Similar differences were also observed in the gender-based subgroup analysis. There were no differences detected between MSA and PD patients. In MSA patients, significant correlation was found between vitamin A, folate, or vitamin C and relevant clinical scales or laboratory findings. In addition, ROC analysis showed potential diagnostic value of the combination of vitamin A, folate, and vitamin C in distinguishing MSA patients from healthy controls. Conclusion: There were significant changes in the blood vitamin spectrums of MSA patients, suggesting that dysregulation of vitamins homeostasis might play an important role in the pathogenesis of MSA.

The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases.

A member of the interleukin (IL)-1 superfamily was IL-36, which contained IL-36α, IL-36ß, IL-36γ, and IL-36Ra. Heterotrimer complexes, consisting of heterodimeric receptor complexes and IL-36 agonist, gave signals through intracellular functional domains, so as to bind to downstream proteins and induce inflammatory response. IL-36 agonists upregulated mature-associated CD80, CD86, MHCII, and inductively produced several pro-inflammatory cytokines through the IL-36R-dependent manner in dendritic cells (DCs). Besides, DCs had the ability to initiate the differentiation of helper T (Th) cells. Up to date, the role of IL-36 in immunity, inflammation and other diseases is of great importance. Additionally, autoimmune diseases were characterized by excessive immune response, resulting in damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases were related to inflammatory response. In this review, we will conclude the recent research advances of IL-36 in the occurrence and development of autoimmune diseases, which may provide new insight for the future research and the treatment of these diseases.

The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases.

Interleukin-38 (IL-38), a new cytokine of interleukin-1 family (IL-1F), is expressed in the human heart, kidney, skin, etc. Recently, new evidence indicated that IL-38 is involved in the process of different autoimmune diseases. Autoimmune diseases are a cluster of diseases accompanied with tissue damage caused by autoimmune reactions, including rheumatoid arthritis (RA), psoriasis, etc. This review summarized the links between IL-38 and autoimmune diseases, as well as the latest knowledge about the function and regulatory mechanism of IL-38 in autoimmune diseases. Especially, this review focused on the differentiation of immune cells and explore future prospects, such as the application of IL-38 in new technologies. Understanding the function of IL-38 is helpful to shed light on the progress of autoimmune diseases.

Long Noncoding RNA 00472: A Novel Biomarker in Human Diseases.

Long non-coding RNAs (lncRNAs) play important roles in human diseases. They control gene expression levels and influence various biological processes through multiple mechanisms. Functional abnormalities in lncRNAs are strongly associated with occurrence and development of various diseases. LINC00472, which is located on chromosome 6q13, is involved in several human diseases, particularly cancers of the breast, lung, liver, osteosarcoma, bladder, colorectal, ovarian, pancreatic and stomach. Importantly, LINC00472 can be used as a biomarker for breast cancer cell sensitivity to chemotherapeutic regimens, including doxorubicin. LINC00472 is regulated by microRNAs and several signaling pathways. However, the significance of LINC00472 in human diseases has not been clearly established. In this review, we elucidate on the significance of LINC00472 in various human diseases, indicating that LINC00472 may be a diagnostic, prognostic as well as therapeutic target for these diseases.

MicroRNA­15a­5p­targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells.

MicroRNAs (miRNAs) have been reported to have important regulatory roles in the progression of several types of cancer, including cervical cancer (CC). However, the biological roles and regulatory mechanisms of miRNAs in CC remain to be fully elucidated. The aim of the present study was to examine the functions of miRNAs in CC and the possible mechanisms. Using a microarray, it was identified that miRNA­15a­5p (miR­15a­5p) was one of the most downregulated miRNAs in CC tissues compared with adjacent noncancerous tissues. The low expression of miR­15a­5p was observed in CC tumor tissues with distant metastasis and in CC cell lines. In addition, the effects of miR­15a­5p upregulation on cell viability, apoptosis, invasion and migration of CC cells were investigated using CCK­8, flow cytometry, Transwell and wound healing assays, respectively. It was demonstrated that upregulation of miR­15a­5p significantly suppressed the viability, migration and invasion, and promoted the apoptosis of SiHa and C­33A cells. Furthermore, yes­associated protein 1 (YAP1), a well­known oncogene, was confirmed to be directly targeted by miR­15a­5p and was found to be negatively regulated by miR­15a­5p. Further correlation analysis indicated that miR­15a­5p expression was negatively correlated with YAP1 expression in CC tissues. Notably, overexpression of YAP1 abrogated the tumor suppressive effects of miR­15a­5p in CC cells. Taken together, these present findings indicated that the miR­15a­5p/YAP1 axis may provide a novel strategy for the clinical treatment of CC.

Inhibition of Histone H3K27 Acetylation Orchestrates Interleukin-9-Mediated and Plays an Anti-Inflammatory Role in Cisplatin-Induced Acute Kidney Injury.

Nephrotoxicity is a major side effect of cisplatin (CP)- and platinum-related chemotherapy, and inflammation contributes to disease pathogenesis. Interleukin-9 (IL-9) is a pleiotropic cytokine associated with inflammation. Here, we investigated the key role of IL-9 as a regulator of protective mechanisms in CP-induced acute kidney injury (AKI). We observed that IL-9 was decreased not only in a CP-induced AKI mouse model but also in THP-1 and RAW264.7 cell lines. Seventy-two hours post-CP injection, renal dysfunction and tubule injury were significantly attenuated in IL-9 overexpression adeno-associated virus 9 (AAV9)-treated mice. The levels of serum urea, serum creatinine, kidney injury molecule-1 (KIM-1), and histological damage were partially diminished following treatment with IL-9. The renoprotective effects of IL-9 may be attributed to the regulation of cytokines, and we found that IL-9 acted on macrophages in a regulatory manner, promoting an anti-inflammatory phenotype. Furthermore, IL-9 enhanced the suppression of macrophage-driven renal inflammation. Inhibition of H3K27 acetylation orchestrated IL-9-mediated renoprotection in CP-induced AKI. Thus, our findings indicate novel and potent anti-inflammatory properties of IL-9 that confer preservation of kidney function and structure in CP-induced AKI, which may counteract kidney disease procession.

Involvement of p53-dependent apoptosis signal in antitumor effect of Colchicine on human papilloma virus (HPV)-positive human cervical cancer cells.

Colchicine, a plant-derived alkaloid with relatively low toxicity on normal human epidermal keratinocytes (HEKn), has selective inhibitory effect on the growth of CaSki (HPV16-positive) and HeLa (HPV18-positive) human cervical cancer cell lines via the induction of apoptosis. Colchicine (2.5, 5.0 and 10.0 ng/ml) significantly reduced the expression of human papilloma virus (HPV) 16 E6/E7 mRNA and protein in CaSki and HeLa cells. Moreover, reduced expression of E6 and E7 induced by Colchicine resulted in the up-regulation of tumor suppressor proteins, p53 and Rb, as well as down-regulation of phospho Rb (pRb) protein. In addition, Bax, cytosolic cytochrome c and cleaved caspase-3 protein were increased while Bcl-2 protein was decreased significantly by 48 h of Colchicine treatment. These results implied that Colchicine could be explored as a potent candidate agent for the treatment and prevention of HPV-associated cervical cancer without deleterious effects.

[Analysis of the diagnosis and treatment of recurrent vulvovaginal candidiasis in 80 cases].

OBJECTIVE: To investigate the appropriate therapy for treating recurrent vulvovaginal candidiasis (RVVC). METHODS: Individual consolidated and maintenance therapy were chosen according to fungal culture of vaginal secretion and antifungal drug sensitivity per month as one therapy duration. Drugs were used orally and vaginally together to consolidate the therapy. Oral drugs were fluconazole (0.15 qw after 0.15 q3d for 2 times) or ketoconazole (0.2, bid for 3 days ) or itraconazole (0.2 bid for 3 days ). After Nystain (400 000 unit qn for 7 days ) or clotrimazole(0.1 qn for 7 days) or amphotericin B (0.01 qn for 6 days ) being vaginally used, Living preparation of lactobacillus (0.25 qn for 5 days) was vaginally used. The therapy was continued for 2 to 5 therapy durations after the symptoms disappeared with negative fungal culture. RESULTS: Among 80 cases of RVVC, C. albicans was mostly detected (74%), C. glabrata was 20%. The susceptivity to candidas of oral agents revealed that the sensitive rare of ketoconazole, fluconazole and itraconazole were (91.3%), (81.3%) and (62.5%), respectively. As for vaginal agents, nystain and amphotericin B were 100% sensitive, clotrimazole was 92.5%sensitive, miconazole was 55.0% sensitive. The remote cure of 3 and 6 therapy durations after discontinuing for 12 months was 78.9% and 90.4% CONCLUSION: The predominant pathogen in RVVC is C. albicans. The effective measures to cure RVVC are to choose sensitive drugs for individual consolidated, maintenance therapy and restore vaginal acidic environment.

[Study on the extraction process for free isofraxidin and hydrolytic condition of combined isofraxidin in Ciwujia with orthogonal design].

OBJECTIVE: To optimize the extraction and hydrolytic condition of isofraxidin in Ciwujia. METHODS: The study was carried out through orthogoral experimental design. The content of isofraxidin was determined as marker to evaluate the effect on the extraction and hydrolytic condition of different process. RESULTS: The optimum extraction condition was 12 times methanol and 3 times for sixty minutes every time. And the optimum hydrolytic condition was that hydrolysis for two hours, ten times amount of 15% sulfuric acid at 100 degrees C.

[Clinical analysis of 22 cases of Bartholin gland cyst or abscess treated with trocar puncture].

This study was designed to observe the effects of trocar puncture in the treatment of Bartholin gland cyst or abscess. The cure rate of these 22 cases was 100%, and no relapse of the disease occurred during the follow-up lasting for 5 to 12 months. Trocar puncture proves to be effective in the treatment of bartholin gland cyst or abscess, especially when the size is less than 3.0 cm.