Multifunctional DNA-Based Hydrogel Promotes Diabetic Alveolar Bone Defect Reconstruction.

Diabetic alveolar bone defect (DABD) causes persistent bacterial infection, prolonged inflammation, and delayed bone healing, making it a considerable clinical challenge. In this study, by integrating silver nanoclusters (AgNCs) and M2 macrophage-derived extracellular vesicles (M2EVs), a multifunctional DNA-based hydrogel, called Agevgel, is developed with antibacterial, anti-inflammatory, immunomodulatory, and osteogenic properties to promote DABD rebuilding. AgNCs are tightly embedded into the DNA scaffolds and exhibit effective anti-bacterial activity, while immunomodulatory M2EVs are encapsulated within the shape-variable DNA scaffolds and exhibit potent anti-inflammatory and osteogenic properties. The results reveal that Agevgel effectively prolongs the local retention time and bioactivity of M2EVs in vivo. In particular, the sustained release of M2EVs can last for at least 7 days when applying Agevgel to DABD. Compared to free M2EVs or Aggel (AgNCs encapsulated within the DNA hydrogel) treatments, the Agevgel treatment accelerates the defect healing rate of alveolar bone and dramatically improves the trabecular architecture. Mechanistically, Agevgel plays a key role in regulating macrophage polarization and promoting the expression of proliferative and osteogenic factors. In summary, Agevgel provides a comprehensive treatment strategy for DABD with a great clinical translational value, highlighting the application of DNA hydrogels as an ideal bioscaffolds for periodontal diseases.

Antibacterial and DNA-Based Hydrogels In Situ Block TNF-α to Promote Diabetic Alveolar Bone Rebuilding.

Alveolar bone injury under diabetic conditions can severely impede many oral disease treatments. Rebuilding diabetic alveolar bone in clinics is currently challenging due to persistent infection and inflammatory response. Here, an antibacterial DNA-based hydrogel named Agantigel is developed by integrating silver nanoclusters (AgNCs) and tumor necrosis factor-alpha (TNF-α) antibody into DNA hydrogel to promote diabetic alveolar bone regeneration. Agantigel can effectively inhibit bacterial growth through AgNCs while exhibiting negligible cytotoxicity in vitro. The sustained release of TNF-α antibody from Agantigel effectively blocks TNF-α and promotes M2 polarization of macrophages, ultimately accelerating diabetic alveolar bone regeneration in vivo. After 21 days of treatment, Agantigel significantly accelerates the defect healing rate of diabetic alveolar bone up to 82.58 ± 8.58% and improves trabecular architectures compared to free TNF-α (42.52 ± 15.85%). The results imply that DNA hydrogels are potential bio-scaffolds helping the sustained release of multidrug for treating DABI or other oral diseases.

Potential mechanism of the AgNCs-hydrogel in promoting the regeneration of diabetic infectious wounds.

Diabetic infectious wound treatment is challenging due to insistent wound infections. To treat such complicated pathological diabetic infectious wounds, multifunctional materials need to be developed, and their mechanisms need to be understood. Here, we developed a material termed AgNCs-hydrogel, which is a multifunctional DNA hydrogel used as dressings by integrating it with antibacterial silver nanoclusters. The AgNCs-hydrogel was applied to promote the regeneration of diabetic infectious wounds in mice because it exhibited superior antibacterial activity and effective ROS-scavenging properties. Based on skin proteomics, we explored the potential mechanism of the AgNCs-hydrogel in treating mouse skin wounds. We found that the AgNCs-hydrogel can regulate some key proteins located primarily in the extracellular exosomes, involved in the negative regulation of the apoptotic process, and perform ATP binding to accelerate diabetic infected wound closure. Therefore, this study provided a multifunctional AgNCs-hydrogel and revealed its potential mechanism in promoting the regeneration of diabetic infectious wounds.

Role of Seipin in Human Diseases and Experimental Animal Models.

Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). BSCL2 gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia's encephalopathy), and BSCL2-associated motor neuron diseases. Abnormal expression of seipin has also been found in hepatic steatosis, neurodegenerative diseases, glioblastoma stroke, cardiac hypertrophy, and other diseases. In the current study, we comprehensively summarise phenotypes, underlying mechanisms, and treatment of human diseases caused by BSCL2 gene mutations, paralleled by animal studies including systemic or specific Bscl2 gene knockout, or Bscl2 gene overexpression. In various animal models representing diseases that are not related to Bscl2 mutations, differential expression patterns and functional roles of seipin are also described. Furthermore, we highlight the potential therapeutic approaches by targeting seipin or its upstream and downstream signalling pathways. Taken together, restoring adipose tissue function and targeting seipin-related pathways are effective strategies for CGL2 treatment. Meanwhile, seipin-related pathways are also considered to have potential therapeutic value in diseases that are not caused by BSCL2 gene mutations.

Single Nucleotide Polymorphism of Genes Associated with Metabolic Fatty Liver Disease.

AIMS: The present study aimed to reveal the relationship between single nucleotide polymorphism (SNP) of PNPLA3, TM6SF2, MBOAT7, GATAD2A, and STAT3 genes and metabolism-related fatty liver disease (MAFLD), so as to provide a research basis for further exploring the diagnosis and treatment of diseases at the molecular level. METHODS: A total of 564 patients were included in the physical examination center of Xinjiang Karamay People's Hospital. They were divided into an MAFLD case group and a healthy control group. The whole blood DNA of each sample was extracted by a whole blood genomic DNA extraction kit, and the genotypes of PNPLA3 rs738409, MBOAT7 rs64173, STAT3 rs744166, TM6SF2 rs58542926, and GATAD2A rs4808199 were performed; after adjusting for confounding factors, the additive model, dominant model, and recessive model of each gene were analyzed by multivariate logistic regression. RESULTS: The CC genotype of the PNPLA3 gene rs738409 and the TT genotype of the MBOAT7 gene rs64173 are risk factors in the occurrence of MAFLD. The AA genotype of the STAT3 gene rs744166 is a protective factor of MAFLD, while TM6SF2 rs58542926 and GATAD2A rs4808199 show no significant correlation with MAFLD.

Comparison of lateral entry and crossed entry pinning for pediatric supracondylar humeral fractures: a meta-analysis of randomized controlled trials.

BACKGROUND: Closed reduction and pinning entry fixation have been proposed as treatment strategies for displaced supracondylar humeral fractures (SCHFs) in children. However, controversy exists regarding the selection of the appropriate procedure. Hence, this meta-analysis was conducted to compare the effect of lateral and crossed pin fixation for pediatric SCHFs, providing a reference for clinical treatment. METHODS: Online databases were systematically searched for randomized controlled trials (RCTs) comparing lateral pinning entry and crossed pinning entry for children with SCHFs. The primary endpoints were iatrogenic ulnar nerve injuries, complications, and radiographic and functional outcomes. RESULTS: Our results showed that iatrogenic ulnar nerve injuries occurred more commonly in the crossed pinning entry group than in the lateral pinning entry group (RR = 4.41, 95% CI 1.97-9.86, P < 0.05). However, its risk between the crossed pinning with mini-open incisions group and the lateral pinning entry group was not significantly different (RR = 1.58, 95% CI 0.008-29.57, P = 0.76). The loss of reduction risk was higher in the lateral pinning entry group than in the crossed pinning entry group (RR = 0.66; 95% CI 0.49-0.89, P < 0.05). There were no significant differences in the carry angle, Baumann angle, Flynn scores, infections, and other complications between these two groups. CONCLUSIONS: The crossed pinning entry with mini-open incision technique reduced the loss of reduction risk, and the risk of iatrogenic ulnar nerve injury was lower than in the lateral pinning entry group. The crossed pinning entry with mini-open incision technique is an effective therapeutic strategy for managing displaced supracondylar humeral fractures in children.

Comparison of Laminoplasty vs. Laminectomy for Cervical Spondylotic Myelopathy: A Systematic Review and Meta-Analysis.

OBJECTIVES: Laminoplasty (LP) and laminectomy (LC) with or without fusion are recommended as treatment procedures for cervical spondylotic myelopathy (CSM). The purpose of this study is to conduct a meta-analysis to analyze the results of CSM patients undergoing LP or LC surgery. METHODS: We systematically and comprehensively searched Web of Science, Cochrane Library, PubMed, EMBASE, OVID, VIP database, Google Scholar, Chinese Bio-medicine Literature database, and China Scientific Journal Full-text database to July 2021 for randomized controlled trials (RCTs) and observational case series that compared LP and LC in patients with CSM. The main endpoints were the surgical process, radiographic outcomes, clinical outcomes, and surgical complications. RESULTS: A total of 19 were included the inclusion criteria in this meta-analysis (n = 4,348 patients). There was no significant difference in range of motion (ROM), sagittal vertical axis (SVA), Japanese Orthopedic Association (JOA), Cobb angle, visual analog scale (VAS), cervical curvature index (CCI), Nurick score, Neck Dysfunction Index (NDI), and complications. LP was found to be superior than LC in terms of complications of C5 radiculopathy and surperficial infection. CONCLUSION: Our results indicate that LP can achieve better results in C5 radiculopathy and superficial infection in surgical treatment of CSM compared with LC. Further high-quality research is warranted to further verify our findings. SYSTEMATIC REVIEW REGISTRATION: PRISMA: CRD42018107070.

[Nomograma prediction of the surgical treatment in triad of elbow].

OBJECTIVE: To establish an individualized Nomogram prediction model for predicting the postoperative recovery of patients with triad of elbow (TE) by analyzing risk factors of triad of elbow joint. METHODS: From January 2012 to December 2018, 116 patients with TE who met the criteria were collected. The independent risk factors were screened by univariate Logistic regression analysis. The statistically significant risk factors were included in the multivariate Logistic regression model. The R software was used to establish the Nomogram diagram model to predict the postoperative recovery of TE patients. C index was used to verify the discrimination, Calibration plot of the model, and the decision curve (decision curve analysis, DCA) to verify the net clinical benefit rate of the model. RESULTS: Forty-four of the 116 patients with TE developed symptoms after operation, with an incidence of 37.93%. Age (OR=1.930, 95% CI 1.418 to 2.764), work (OR=6.153, 95%CI 1.466 to 31.362), smoking(OR=4.463, 95%CI 1.041 to 2.291), the Mason of radial head(OR=1.348, 95%CI 2.309 to 9.348), the Regan-Morrey of coronal process (OR=4.424, 95%CI 1.751 to 2.426) and postoperative elbow immobilization time(OR=7.665, 95%CI 1.056 to 5.100) were independent risk factors for postoperative recovery of TE (P<0.05). The C-index of Nomogram plot was 0.716. Calibration plot showed that the predictive model was consistent, and the DCA curve showed satisfactory clinical net benefit. CONCLUSION: The Nomogram for predicting postoperative results of TE patients based on six independent risk factors:age, work, smoking, Mason classification of radial head, Regan-Morrey classification of coronal process and immobilization time of elbow joint after operation, has good distinguishing capacity and consistency. Thepredictive model could help clinicians to identify high risk population and establish appropriate intervention strategies.

MicroRNA profiling of serum exosomes in patients with osteosarcoma by high-throughput sequencing.

The microRNA expression profile of plasma exosomes in osteosarcoma needs to be further explored. The present study intends to investigate the practicality of plasma exosomal miRNAs as novel biomarkers of osteosarcoma. In the study, exosome-like vesicles were purified from the plasma of patients with osteosarcoma and healthy control. Differential centrifugation was used. The purified vesicles which ranged from 50 to 100 nm in size were identified as exosomes by transmission electron microscopy and western blot. Validating assays in vitro and in vivo were performed via CCK8, reverse transcription-quantitative PCR, flow cytometry, transwell and wound healing assays and xenograft model. High-throughput sequencing identified that 57 miRNAs, 20 of which were upregulated and 37 downregulated, were differentially expressed in patients with osteosarcoma and healthy control (p<0.01; fold change ≥3). In comparison to the controls, the expression levels of miR-92a-3p, miR-130a-3p, miR-195-3 p, miR-335-5 p, let-7i-3p were upregulated in the exosomes from patients with osteosarcoma with statistical significance. Studies in vitro and in vivo have proved that osteosarcoma-secreted exosomes from miR-195-3 p upregulated 143B osteosarcoma cells promote cell proliferation and invasion. Overall, the present study identified exosomal miRNAs with dysregulated expression in patients with osteosarcoma, and they may have potential as targets for the treatment of patients with osteosarcoma.

Maternal serum trimethylamine-N-oxide is significantly increased in cases with established preeclampsia.

PURPOSE: To compare the levels of trimethylamine-N-oxide (TMAO) in sera of normal and preeclamptic pregnancies and to explore whether serum TMAO level was associated with the severity of preeclampsia. MATERIALS AND METHODS: Eighty-six pregnant women in the third trimester were enrolled in this case control study. Levels of TMAO were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting serum samples from 43 preeclamptic women and 43 normotensive controls. Clinical characteristics, serum biomarkers of inflammation (IL-1ß) and biomarkers of endothelial dysfunction (sVCAM-1, sFlt-1) were assessed. RESULTS: TMAO levels were significantly higher in women with preeclampsia than those with normal pregnancy. The serum levels of TMAO were positively correlated with systolic blood pressure (r = 0.602, P < 0.001), urinary protein levels (r = 0.557, P < 0.001) and the serum levels of IL-1ß (r = 0.633, P < 0.001), sVCAM-1 (r = 0.719, P < 0.001) as well as sFlt-1 (r = 0.763, P < 0.001) in patients with PE. CONCLUSIONS: Elevated TMAO levels are associated with higher risk of preeclampsia and correlate with increased systemic inflammation and endothelial dysfunction. Further validation of these findings with more robust multicenter prospective and longitudinal characterization of maternal serum TMAO in pregnancy may be carried out in subsequent investigations to determine its suitability as a predictive biomarker for preeclampsia.

Maternal obesity and risk of cerebral palsy in children: a systematic review and meta-analysis.

AIM: Several studies have examined the links between maternal obesity and the risk of cerebral palsy (CP) in children, with inconsistent results. The aim of our study was to investigate whether maternal obesity is associated with increased risk of CP in offspring by using meta-analysis. METHOD: PubMed and Web of Science were searched until August 2017. Observational studies relevant to the maternal obesity and risk of CP in children were extracted and compiled. Meta-analyses were performed for different obesity levels and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS: A total of five cohort studies involving 12 324 cases and 7 919 288 participants were included in our meta-analysis. The pooled crude and adjusted ORs (95% CIs) were 1.65 (1.38-1.98) and 1.51 (1.24-1.84) respectively. Additionally, the pooled OR (95% CI) for CP in offspring in relation to maternal obesity class I (body mass index [BMI] 30.0-34.9), class II (BMI 35.0-39.9), and class III (BMI≥40.0) compared with normal weight during prepregnancy or pregnancy was 1.31 (1.15-1.50), 1.65 (1.34-2.02), and 2.37 (1.91-2.94) respectively. INTERPRETATION: This meta-analysis demonstrated that increasing grades of maternal obesity are associated with a higher risk of CP in offspring. WHAT THIS PAPER ADDS: Meta-analysis demonstrates a significant positive association between maternal obesity and the risk of cerebral palsy (CP) in children. Subgroup analysis indicates that higher grades of maternal obesity are associated with increasing risk of CP.

Maternal C-reactive protein and cytokine levels during pregnancy and the risk of selected neuropsychiatric disorders in offspring: A systematic review and meta-analysis.

The pathophysiology of neuropsychiatric disorders is unclear. Increasing evidence has suggested maternal immune system dysregulation may be implicated in offspring's early brain development and related to an increased risk of neuropsychiatric disorders in offspring. The primary objective of this meta-analysis was to investigate the association of maternal CRP and cytokine levels with offspring's neuropsychiatric disorders. We identified relevant studies following a search of PubMed, Web of Science, EMbase database between January 1971 and February 2018. A meta-analysis was performed on studies which reported the association of prenatal maternal peripheral blood concentrations of CRP and cytokines with offspring's neuropsychiatric disorders. Results were reported according to PRISMA statement. Fifteen studies (six for maternal CRP, nine for maternal cytokines) were included in the meta-analysis, of which 80% were of high methodological quality. Random-effect meta-analysis showed that increasing maternal CRP (OR = 1.31, 95% CI 1.11-1.55, SMD = 0.15, 95% CI 0.06-0.24, P < 0.01), pro-inflammatory cytokine interleukin (IL)-8 (OR = 1.64, 95% CI 1.06-2.55, SMD = 0.27, 95% CI 0.03-0.52, P = 0.03) and anti-inflammatory cytokine IL-10 (OR = 2.16, 95% CI 1.30-3.59, SMD = 0.43, 95% CI 0.14-0.71, P < 0.01) were significantly associated with schizophrenia in offspring. The finding of our meta-analysis has identified significantly altered maternal CRP and cytokine concentrations in schizophrenia, strengthening evidence of maternal immune system dysregulation in neuropsychiatric disorders where inflammatory signals dominate.

B7-H3 Overexpression Predicts Poor Survival of Cancer Patients: A Meta-Analysis.

BACKGROUND: B7-H3 exhibits altered expression in various cancers. However, the correlation between B7-H3 expression and prognosis of cancer patients remains controversial. Therefore, we elicit a meta-analysis to investigate the potential value of B7-H3 in the prognostic prediction in human cancers. MATERIALS AND METHODS: We searched PubMed (last update by June 15th, 2016) to identify studies assessing the effect of B7-H3 on survival of cancer patients. Hazard ratios (HRs) for overall survival (OS), recurrence free survival (RFS) and progression-free survival (PFS) from individual studies were calculated and pooled by using a random-effect or fix-effect model, and heterogeneity and publication bias analyses were also performed. RESULTS: Data from 24 observational studies consisting of 4141 patients were summarized. An elevated baseline B7-H3 was significantly correlated with poor OS (pooled HR = 2.09; 95% CI =1.60-2.74; P < 0.001). Differences across subgroups of tumor type (P = 0.324), year of publication (P = 0.431), ethnicity (P = 0.940), source of HR (P = 0.145), analysis type (P = 0.178) and sample size (P = 0.909) were not significant. Furthermore, high B7-H3 expression also predicted a significantly poor RFS (pooled HR = 1.39; 95% CI = 1.11-1.75; P = 0.004) but not PFS. CONCLUSIONS: This meta-analysis clarifies that elevated B7-H3 expression is significantly associated with poor survival in cancer patients.

[Analysis on complications of elastic nail treating children's long bone fractures].

OBJECTIVE: To analyze the reasons on complications of treatment with elastic nail in children's long bone fracture. METHODS: Sixty-six cases (75 parts of long bone fratures) were treated by elastic nail including 49 male and 17 female. The age ranged from 3 to 17 years, mean 7.8 years. There were 35 femur fractures (2 cases were hibateral), 20 tibia and fibula fractures (12 cases were tibia fractures), 8 radial fractures (1 case was ulna fracture) and 3 humerus fractures. The cases included 4 open fractures and 62 closed fractures. All cases were fresh fractures, no multi-segmental fractures. Three cases associated with brain and chest injuries. These cases were treated by open or closed reduction and internal fixaion with elastic nail. A cast or brace had been used after operation for a month. Following-up included the function of the joint,the bottom of the nail and the callus. Complications were timely recorded. RESULTS: All the patients were followed-up for 12 to 29 months, averaged 17 months. The cases occurrenced compilications including 2 cases of nonunion, 2 of new fracture, 1 of displacment, 4 of joint dysfunction, 3 of irritation of the bottom of the nail and 1 malunion. CONCLUSION: Strict indication, well design,canonical operation is a good way to avoid compliacations. At the same time,early treatment can reduce the sequela.

[The therapeutic strategy of humeral supracondylar fracture with never injury in children].

OBJECTIVE: To determine the clinical features and therapeutic strategy of humeral supracondylar fractures with nerve injuries in children. METHODS: From June 2000 to December 2006,28 patients of humeral supracondylar fracture (Gartlang III) with never injuries were analyzed. Twenty-four patients were close injuries and the others were open. Sixteen cases (group A)were treated with close reduction and K-wires fixation. Twelve cases (group B)were treated with open reduction and nerve exploration, among them, contusive nerve injuries in 8 cases, incarceration in 3, complete neurotmesis in 1. RESULTS: The symptoms of nerve injuries of 28 cases recovered completely within 4 to 6 weeks in 13 cases, 8 to 10 weeks in 2 cases and 12 weeks in 1 case in group A, meanwhile, within 4 to 6 weeks in 6 cases, 8 to 10 weeks in 3 cases and 12 to 16 weeks in 3 cases in group B. CONCLUSION: Most nerve injuries in humeral supracondylar fractures in children can be cured after close reduction of the fracture. Sometimes, open reduction and nerve exploration are necessary, which has important practical significance.