Mesenchymal Stem Cell-Derived Exosomes: A Novel Approach to Diabetes-Associated Cognitive Impairment.

The progression of diabetes frequently results in a myriad of neurological disorders, including ischemic stroke, depression, blood-brain barrier impairment, and cognitive dysfunction. Notably, diabetes-associated cognitive impairment, a prevalent comorbidity during the course of diabetes, progressively affects patients' cognitive abilities and may reciprocally influence diabetes management, thereby severely impacting patients' quality of life. Extracellular vesicles, particularly nanoscale exosomes, have garnered considerable attention in recent years. These exosomes carry and transfer various functional molecules, such as proteins, lipids, and diverse non-coding RNAs, serving as novel regulators and communicators in intercellular interactions. Of particular interest, mesenchymal stem cell-derived exosomes (MSC-Exos) have been reported to traverse the blood-brain barrier and ameliorate intracerebral pathologies. This review elucidates the role of MSC-Exos in diabetes-related cognitive impairment, with a focus on their applications as biomarkers, modulation of neuronal regeneration and synaptic plasticity, anti-inflammatory properties, antioxidative effects, and their involvement in regulating the functionality of ß-amyloid proteins during the course of cognitive impairment. The immense therapeutic potential of MSC-Exos in the treatment of diabetes-induced cognitive dysfunction is emphasized.

Efficacy of electroacupuncture in assisting postoperative healing of distal radius fractures: study protocol for a randomized controlled trial.

BACKGROUND: Manual reduction and surgical treatment are common methods for distal radius fractures (DRFs). The existing literature suggests that postoperative combined rehabilitation treatment and medication are effective for the healing of DRFs. However, the side effects of these treatments remain to be solved. Previous studies have shown that electroacupuncture (EA) can effectively relieve wrist swelling and improve the joint function in patients with DRFs, but more evidence is needed to prove the effectiveness of EA. This trial aims to explore the efficiency and feasibility of combined EA treatment in postoperative treatment of DRFs compared with routine treatment. METHODS: This is a parallel randomized controlled trial. A total of 222 patients diagnosed with moderate DRFs will be recruited and randomly assigned to an EA group or a routine treatment group at a ratio of 1:1. Routine treatment group will receive medication and rehabilitation. Yangxi (LI 5), Yangchi (TE 4), Yanggu (SI 5), Hegu (LI 4), and Taiyuan (LU 9) will be selected in the EA group for intervention three times a week on the basis of routine treatment. Both groups will receive 8 weeks of treatment and 4 weeks of follow-up. The primary outcome will be ulnar positive variance. The secondary outcomes will include radiographic healing rate, bone strength, hemorheological indices, serum biochemical indicators and inflammatory factors, grip strength, wrist swelling score, patient-rated wrist evaluation, disabilities of arm, shoulder and hand, and visual analogue scale. Outcomes will be evaluated at baseline, postoperative 3rd day, 2nd, 4th, 6th, 8th, and 12th weeks. DISCUSSION: The results of this study will help establish a more optimized scheme to treat patients with DRFs. Trial registration Chinese Clinical Trial Registry ChiCTR2200062857. Registered on 21 August 2022, www.chictr.org.cn/com/25/showproj.aspx?proj=175567 .

Clinical and genetic characteristics of two cases with Williams-Beuren syndrome.

Herein, we describe 2 cases of Williams-Beuren syndrome (WBS). In both cases, the patients exhibited mental retardation, characteristic facial features, and indirect inguinal hernia. Case 1, a girl aged 2 years and 5 months old, presented with hypercalcemia, and in case 2, a boy aged 4 years and 11 months old, the disorder manifested as infantile spasms, supravalvular aortic stenosis, and pulmonary stenosis. Brain MRI revealed no abnormalities in either case. The electroencephalogram of case 2 showed hypsarrhythmia. Case 1 was treated with bisphosphonates and somatropin for hypercalcemia and short stature. Case 2 received antiepileptic drug and ketogenic diet therapy. In both cases, a 7q11.23 deletion including fragment deletion of the GTF21 gene was found, which may be associated with mental retardation. Notably, in case 2, a 921.1kb deletion in Yq11.23 was detected, which has not been reported in WBS before. The deletion of Yq11.23 is located in the AZFc region, which is an important factor in male infertility with primary azoospermia and oligozoospermia. The occurrence of hypercalcemia in case 1 may be related to the deletion of BAZ1B, while the supravalvular aortic stenosis and pulmonary stenosis were associated with deletion of the ELN gene. We explored the clinical and genetic characteristics of WBS to better understand disease.

Repairing effects of glucosamine sulfate in combination with etoricoxib on articular cartilages of patients with knee osteoarthritis.

PURPOSE: To evaluate the repairing effects of glucosamine sulfate combined with etoricoxib on articular cartilages of patients with knee osteoarthritis (KOA). METHODS: A total of 106 KOA patients were randomly divided into control (n = 40) and experimental groups (n = 66) and treated with etoricoxib alone and glucosamine sulfate plus etoricoxib, respectively. Changes in WOMAC score and clinical efficacy were observed. The synovial fluid was extracted. Bone metabolism indices, growth factors, inflammatory factors, matrix metalloproteinases (MMPs), and NO-induced apoptosis-related factors were measured by ELISA. JNK and Wnt5a mRNA levels were determined using RT-PCR. RESULTS: After treatment, the total WOMAC scores of both groups significantly declined (P < 0.05), being lower in experimental group. The total effective rate of experimental group was higher (P < 0.05). BGP and OPG levels rose, especially in experimental group (P < 0.05). CTX-II, COMP, and RANKL levels decreased, particularly in experimental group (P < 0.05). TGF-ß, IGF-1, and FGF-2 levels increased, especially in experimental group (P < 0.05). Both groups, particularly experimental group, had decreased levels of IL-1ß, IL-17, IL-18, TNF-α, MMP-3, MMP-9, and MMP-13 (P < 0.05). JNK and Wnt5a mRNA levels of both groups dropped, which were lower in experimental group (P < 0.05). NO and LPO levels reduced, being lower in experimental group. SOD level rose, especially in experimental group (P < 0.05). CONCLUSION: Glucosamine sulfate plus etoricoxib can repair the articular cartilages of KOA patients. Probably, JNK and Wnt5a are downregulated to inhibit the secretion of MMPs through lowering the levels of inflammatory factors, thereby delaying cartilage matrix degradation. NO-induced chondrocyte apoptosis may be suppressed via the SOD pathway.

[Clinical and genetic analysis of two cases with Rubinstein-Taybi syndrome].

OBJECTIVE: To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS). METHODS: Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c.3779+1G>A and c.5052_c.5053insT, were respectively identified in the 2 patients. Among these, c.3779+1G>A was a previously known pathological mutation, while c.5052_c.5053insT was unreported previously. Both variants were predicted to be pathological. CONCLUSION: Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.

Comparison of Fixed-Bearing and Mobile-Bearing Unicompartmental Knee Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Prior studies have compared fixed-bearing unicompartmental knee arthroplasty (FB-UKA) with mobile-bearing UKA (MB-UKA), suggesting that both procedures have good clinical outcomes. However, which treatment is more beneficial for patients is controversial. The purpose of our study is to evaluate the postoperative outcomes, including the revision rate, complications, functional results, range of motion, and femoral-tibial angle, between the 2 procedures. METHODS: We searched the MEDLINE, EMBASE, Cochrane Library, and Web of Science databases starting from August 2017 to May 2018. The publication date of articles was not restricted. Before we submit our contribution, we have re-searched it again. Articles that directly compared the postoperative outcomes of the 2 prosthesis type were included. RESULTS: A total of 15 comparative studies were included in our meta-analysis. The pooled data indicated no differences between the 2 operation modes in terms of revision rates, complications, and knee function, but earlier failure occurred more frequently with the MB design. CONCLUSION: Both the arthroplasty types provided satisfactory clinical results for patients with classic indications. However, MB-UKA tended to fail in early postoperative years whereas fixed-bearing UKA in later postoperative years. Therefore treatment options should be carefully considered for each patient, and surgeons should still use their personal experience when deciding between these options.

Two Chinese Xia-Gibbs syndrome patients with partial growth hormone deficiency.

BACKGROUND: Heterozygous mutations in the AT-hook DNA-binding motif containing one (AHDC1, OMIM * 615790) gene cause an autosomal dominant multisystem developmental disorder known as Xia-Gibbs syndrome (OMIM #615829). Xia-Gibbs syndrome typically presented with global developmental delay, hypotonia, obstructive sleep apnea, seizures, delayed myelination, micrognathia, and other mild dysmorphic features. METHODS: Description of the clinical materials of two Chinese boys who were diagnosed with Xia-Gibbs syndrome based on clinical presentations and next generation sequencing. Review of clinical features and AHDC1 mutations in previously reported Xia-Gibbs syndrome patients together with our two new patients. RESULTS: The Xia-Gibbs syndrome patients exhibited short stature, hypotonia, global developmental delay, speech delay, simian crease, and mild dysmorphic features. Next generation sequencing revealed de novo heterozygous variants in AHDC1 gene. In addition, laboratory test revealed partial growth hormone deficiency. Both patients underwent growth hormone replacement therapy for 24 and 9 months, respectively, and exhibited good response to the treatment. CONCLUSION: This is the first report of Xia-Gibbs syndrome patients to be treated with growth hormone. Review of previously reported Xia-Gibbs syndrome patient indicated that short stature is a frequent feature of this condition, but its underlying cause needs to be further investigated.