Triple-nerve decompression surgery for the treatment of painful diabetic peripheral neuropathy in lower extremities: A study protocol for a randomized controlled trial

ObjectivesPainful diabetic peripheral neuropathy (DPN) is often refractory to conventional medications. Triple-nerve decompression was proposed for painful DPN due to the frequent involvement of multiple nerve entrapments in diabetes. However, the role of decompressive surgery remains controversial. This trial aims to assess the efficacy of triple-nerve decompression for patients with painful DPN suggestive of nerve entrapment using a randomized controlled trial (RCT) design.Methods and analysisThis trial is a single-center RCT and will be conducted in Shanghai Ninth People's Hospital. Enrolled subjects (n = 74) with painful DPN due to nerve compression, which can be detected by nerve conduction studies, will be randomly allocated at a 1:1 ratio into surgical and non-surgical groups. The primary outcome will be measured by 50% responder rates, which is defined as the proportion of subjects with at least 50% reduction of the mean weekly visual analog score (VAS) of pain from baseline after 6 months of treatment. Mean weekly VAS will be additionally evaluated 1 week (W1), 1 month (M1), and 3 months (M3) after treatment to monitor the changes in pain intensity. The secondary outcomes include two-point discrimination (TPD), Toronto clinical scoring system (TCSS), electrophysiological indexes, hospital anxiety and depression scale (HADS), and the medical outcome study short-form 36-item questionnaire (SF-36). A quantitative analgesic questionnaire (QAQ) will be used as a secondary outcome to quantify the analgesic medication weekly. TPD and TCSS will be conducted at W1, M1, M3, and M6 after treatment. Electrophysiological tests, HADS, and SF-36 will be performed at M3 and M6.Ethics and disseminationEthics approval has been obtained from the Ethics Committee of Shanghai Ninth People's Hospital (SH9H-2-21-T323-2). It was registered on the Chinese Clinical Trial Registry website (http://www.chictr.org.cn) on 16 August 2021 with the number ChiCTR2100050049. Written informed consent will be obtained from all participants. The results of this trial will be disseminated via peer-reviewed journals, mass media, and presentations at national and international academic conferences

NeurimmiRs and Postoperative Delirium in Elderly Patients Undergoing Total Hip/Knee Replacement: A Pilot Study

Objective: Postoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The pathophysiology of this complication is not clear, but identification of risk factors is important for positive postoperative outcomes. The purpose of this study was to investigate the associations between the preoperative expression levels of microRNA (miR)-146a, miR-125b, and miR-181c in cerebrospinal fluid (CSF) and serum and the development and severity of POD.Methods: Forty elderly patients aged 65 years old and older admitted for elective total hip/knee replacement under spinal anesthesia. Preoperatively, baseline cognitive function was assessed using the Mini-Mental State Examination. Each patient was interviewed daily on the first and second postoperative days. Delirium was diagnosed using the Confusion Assessment Method, and delirium severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative serum and CSF miR levels were determined by quantitative real-time PCR (qRT-PCR).Results: POD was detected in 27.5% (11/40) of patients. Up-regulation of miR-146a and miR-181c in CSF and down-regulation of miR-146a in serum were observed preoperatively in patients who developed POD, while patients with and without POD did not differ in serum or CSF levels of miR-125b. Delirious patients had higher CSF/serum ratios of miR-146a and miR-181c levels than non-delirious patients. The lower CSF miR-146a and CSF/serum miR-146a ratios were significantly associated with milder POD severity, represented by a lower MDAS score.Conclusion: The dysregulation of preoperative miR-146a and miR-181c in CSF and serum was associated with the development and severity of POD. These NeurimmiRs might participate in the neuropathogenesis of POD, pending further investigations.Clinical trial registration: this study was registered at ClinicalTrials.gov (NCT02817386)

Age-dependent variations in rumen bacterial community of Mongolian cattle from weaning to adulthood

BackgroundRumen microbes play an important role in ruminant energy supply and animal performance. Previous studies showed that the rumen microbiome of Mongolian cattle has adapted to degrade the rough forage to provide sufficient energy to tolerate the harsh desert ecological conditions. However, little is known about the succession of rumen microbes in different developmental stages of post-weaning Mongolian cattle.MethodsHere, we examined the succession of the rumen microbial composition and structure of 15 post-weaning Mongolian cattle at three developmental stages i.e., 5 months (RM05), 18 months (RM18) and, 36 months (RM36) by using the 16S rRNA gene sequencing method.ResultsWe did not find any age-dependent variations in the ruminal concentrations of any volatile fatty acid (VFA) of Mongolian cattle. The diversity of the rumen bacterial community was significantly lower in RM05 group, which reached to stability with age. Bacteroidetes and Firmicutes were the two dominant phyla among all age groups. Phylum Actinobacteria was significantly higher in RM05 group, phyla Spirochaetes, and Tenericutes were highly abundant in RM18 group, and phyla Proteobacteria and Epsilonbacteraeota were enriched in RM36 group. Genera Prevotella_1, Bacteroides, and Bifidobacterium were abundant in RM05 group. The short chain fatty acid (SCFA) producing bacteria Rikenellaceae_RC9_gut_group showed high abundance in RM18 group and fiber degrading genus Alloprevotella was highly abundant in RM36 group. Random forest analysis identified Alloprevotella, Ileibacterium, and Helicobacter as important age discriminatory genera. In particular, the genera Ruminococcaceae_UCG-005, Bacteroides, Saccharofermentans, and Fibrobacter in RM05, genera [Eubacterium] coprostanoligenes_group, Erysipelotrichaceae_UCG-004, Helicobacter, Saccharofermentans, Papillibacter, and Turicibacter in RM18, and genera Rikenellaceae_RC9_gut_group, Lachnospiraceae_AC2044_group, and Papillibacter in RM36 showed the top interactions values in the intra-group interaction network.ConclusionsThe results showed that rumen microbiota of Mongolian cattle reached to stability and maturity with age after weaning. This study provides some theoretical evidence about the importance of functional specific rumen bacteria in different age groups. Further studies are needed to determine their actual roles and interactions with the hos

Effect of germination on nutritional quality of soybean

Abstract Soybean are rich in functional nutrients such as protein, Essential amino acid, Polyunsaturated fatty acid, minerals, vitamins and dietary fibre which can help maintain optimal body weight, prevent Alzheimer and cardiovascular disease. At the same time, it also contains some anti-nutritional factors which have adverse effects on the digestion, absorption and utilization of nutrients. Cellular and metabolic events are induced by water absorption during seed germination. After absorbing water, soybean dry seeds begin to mobilize organelles and enzyme activities, repair and activate physiological and biochemical processes, and start basic metabolism. After that, by controlling the key factors of metabolism, the cells complete the process of material transformation, energy metabolism, ROS balance, cell wall acidification and looseness, hypocotyl elongation, etc. and finish germination. As a result, cell metabolism causes significant changes in proteins, lipids, sugars, vitamins and minerals, and increases in some beneficial functional nutritional factors for humans and animals, the other anti-nutritional factors decreased obviously, which greatly improved the taste quality and economic value of soybean. This paper introduced the germination physiology, functional nutrients and their metabolic pathways during soybean germination. This study has important reference value for the study of theory and practice technology of soybean germination

The transcriptome sequencing analysis reveals immune mechanisms of soybean fermented powder on the loach (Misgurnus anguillicaudatus) in response to Lipopolysaccharide (LPS) infection

The loach (Misgurnus anguillicaudatus), a small commercial fish that is widely cultivated for its high-quality protein, vitamins, minerals, and essential amino acid, is a member of the genus Misgurnus and the family Cyprinidae. In this study, we gave the LPS-injected loach fermented soybean meal and used transcriptome sequencing to investigate the impact of the fermented soybean powder on the loach’s immune system. 3384 up-regulated genes and 12116 down-regulated genes were found among the 15500 differentially expressed genes, according to the results. The differentially expressed genes were shown to be involved in cellular processes, metabolic processes, cellular anatomical entities, and binding, according to the Go functional annotation. Meanwhile, the KEGG enrichment analysis indicated that the soybean fermented powder treated groups showed significant differences in DNA replication, Nucleotide excision repair, Fanconi anemia pathway, and Base excision repair pathways, suggesting that these pathways are closely related to the enhancement of the immune function of loach by soybean fermented powder. The particular conclusions not exclusively can provide a new conception for the rational utilization of soybean fermented powder but also can provide theoretical guidance for the subsequent healthy breeding of loach

Nose-to-brain delivery of self-assembled curcumin-lactoferrin nanoparticles: Characterization, neuroprotective effect and in vivo pharmacokinetic study

Curcumin (CUR) is a natural polyphenol extract with significant antioxidant and anti-inflammatory effects, which indicates its great potential for neuroprotection. Lactoferrin (LF), a commonly used oral carrier and targeting ligand, has not been reported as a multifunctional nanocarrier for nose-to-brain delivery. This study aims to develop a nose-to-brain delivery system of curcumin-lactoferrin nanoparticles (CUR-LF NPs) and to further evaluate the neuroprotective effects in vitro and brain accumulation in vivo. Herein, CUR-LF NPs were prepared by the desolvation method with a particle size of 84.8 ± 6.5 nm and a zeta potential of +22.8 ± 4.3 mV. The permeability coefficient of CUR-LF NPs (4.36 ± 0.79 × 10−6 cm/s) was 50 times higher than that of CUR suspension (0.09 ± 0.04 × 10−6 cm/s) on MDCK monolayer, indicating that the nanoparticles could improve the absorption efficiency of CUR in the nasal cavity. Moreover, CUR-LF NPs showed excellent protection against Aβ25-35-induced nerve damage in PC12 cells. In vivo pharmacokinetic studies showed that the brain-targeting efficiency of CUR-LF NPs via IN administration was 248.1%, and the nose-to-brain direct transport percentage was 59.7%. Collectively, nose-to-brain delivery of CUR-LF NPs is capable of achieving superior brain enrichment and potential neuroprotective effects

Emerging roles of i-motif in gene expression and disease treatment

As non-canonical nucleic acid secondary structures consisting of cytosine-rich nucleic acids, i-motifs can form under certain conditions. Several i-motif sequences have been identified in the human genome and play important roles in biological regulatory functions. Due to their physicochemical properties, these i-motif structures have attracted attention and are new targets for drug development. Herein, we reviewed the characteristics and mechanisms of i-motifs located in gene promoters (including c-myc, Bcl-2, VEGF, and telomeres), summarized various small molecule ligands that interact with them, and the possible binding modes between ligands and i-motifs, and described their effects on gene expression. Furthermore, we discussed diseases closely associated with i-motifs. Among these, cancer is closely associated with i-motifs since i-motifs can form in some regions of most oncogenes. Finally, we introduced recent advances in the applications of i-motifs in multiple areas

The Function of Fucosylation in Progression of Lung Cancer

Lung cancer is a disease that influences human health and has become a leading cause of cancer mortality worldwide. However, it is frequently diagnosed at the advanced stage. It is necessary by means of biology to identify specific lung tumor biomarkers with high sensitivity. Glycosylation is one of the most important post-translational modifications and is related to many different diseases. It is involved in numerous essential biological processes, such as cell proliferation, differentiation, migration, cell-cell integrity and recognition, and immune modulation. However, little was known about deregulation of glycosylation in lung cancer and contribution to tumor–microenvironment interactions. Among the numerous glycosylations, fucosylation is the most common modification of glycoproteins and glycosylated oligosaccharides. Increased levels of fucosylation have been detected in various pathological conditions, as well as in lung cancer. In this article, we reviewed the role of fucosylation in lung cancer. We highlighted some of the fucosylation alterations currently being pursued in sera or tissues of lung cancer patients. Moreover, we elaborated on the regulation mechanism of fucosylation in proliferative invasion and metastasis of lung tumor cells. In summary, alterations in fucosylation provide potential biomarkers and therapeutic targets in lung cancer

Baseline whole-lung CT features deriving from deep learning and radiomics: prediction of benign and malignant pulmonary ground-glass nodules

ObjectiveTo develop and validate the model for predicting benign and malignant ground-glass nodules (GGNs) based on the whole-lung baseline CT features deriving from deep learning and radiomics.MethodsThis retrospective study included 385 GGNs from 3 hospitals, confirmed by pathology. We used 239 GGNs from Hospital 1 as the training and internal validation set; 115 and 31 GGNs from Hospital 2 and Hospital 3 as the external test sets 1 and 2, respectively. An additional 32 stable GGNs from Hospital 3 with more than five years of follow-up were used as the external test set 3. We evaluated clinical and morphological features of GGNs at baseline chest CT and extracted the whole-lung radiomics features simultaneously. Besides, baseline whole-lung CT image features are further assisted and extracted using the convolutional neural network. We used the back-propagation neural network to construct five prediction models based on different collocations of the features used for training. The area under the receiver operator characteristic curve (AUC) was used to compare the prediction performance among the five models. The Delong test was used to compare the differences in AUC between models pairwise.ResultsThe model integrated clinical-morphological features, whole-lung radiomic features, and whole-lung image features (CMRI) performed best among the five models, and achieved the highest AUC in the internal validation set, external test set 1, and external test set 2, which were 0.886 (95% CI: 0.841-0.921), 0.830 (95%CI: 0.749-0.893) and 0.879 (95%CI: 0.712-0.968), respectively. In the above three sets, the differences in AUC between the CMRI model and other models were significant (all P < 0.05). Moreover, the accuracy of the CMRI model in the external test set 3 was 96.88%.ConclusionThe baseline whole-lung CT features were feasible to predict the benign and malignant of GGNs, which is helpful for more refined management of GGNs