Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Electroconvulsive therapy (ECT) is an interventional technique capable of highly effective neuromodulation in major depressive disorder (MDD), but its antidepressant mechanism remains unclear. By recording the resting-state electroencephalogram (RS-EEG) of 19 MDD patients before and after ECT, we analyzed the modulation effect of ECT on the resting-state brain functional network of MDD patients from multiple perspectives: estimating spontaneous EEG activity power spectral density (PSD) using Welch algorithm; constructing brain functional network based on imaginary part coherence (iCoh) and calculate functional connectivity; using minimum spanning tree theory to explore the topological characteristics of brain functional network. The results show that PSD, functional connectivity, and topology in multiple frequency bands were significantly changed after ECT in MDD patients. The results of this study reveal that ECT changes the brain activity of MDD patients, which provides an important reference in the clinical treatment and mechanism analysis of MDD.
Humans ; Depressive Disorder, Major/therapy* ; Electroconvulsive Therapy ; Brain ; Algorithms ; Electroencephalography

Electromagnetic stimulation is an important neuromodulation technique that modulates the electrical activity of neurons and affects cortical excitability for the purpose of modulating the nervous system. The phenomenon of inverse stochastic resonance is a response mechanism of the biological nervous system to external signals and plays an important role in the signal processing of the nervous system. In this paper, a small-world neural network with electrical synaptic connections was constructed, and the inverse stochastic resonance of the small-world neural network under electromagnetic stimulation was investigated by analyzing the dynamics of the neural network. The results showed that: the Levy channel noise under electromagnetic stimulation could cause the occurrence of inverse stochastic resonance in small-world neural networks; the characteristic index and location parameter of the noise had significant effects on the intensity and duration of the inverse stochastic resonance in neural networks; the larger the probability of randomly adding edges and the number of nearest neighbor nodes in small-world networks, the more favorable the anti-stochastic resonance was; by adjusting the electromagnetic stimulation parameters, a dual regulation of the inverse stochastic resonance of the neural network can be achieved. The results of this study provide some theoretical support for exploring the regulation mechanism of electromagnetic nerve stimulation technology and the signal processing mechanism of nervous system.
Action Potentials/physiology* ; Computer Simulation ; Models, Neurological ; Stochastic Processes ; Neurons/physiology* ; Electromagnetic Phenomena

Objective:To analyze the relationship between plasma uranium concentration and renal injury.Methods:A case-control study was conducted in Hunan province, involving 102 renal injury cases and 102 matched controls. The association between plasma uranium concentration and renal injury was analyzed using conditional logistic regression models, and the dose-response relationship was analyzed through restricted cubic spline regression. The linear regression model and Spearman correlation were used to analyze the association between plasma uranium concentration and renal injury indicators.Results:The median of plasma uranium concentration was 8.94 ng/L in all subjects and 10.19 ng/L in the case group. The plasma uranium may be a risk factor for renal injury, with a dose-response relationship between the both representing nonlinear association ( χ2=5.15, P<0.05). The risk of renal injury was 4.21 times higher in the group exposed to highest uranium concentration than that in the group exposed to lowest uranium concentration. Plasma uranium concentration was closely related to glomerular filtration rate, serum creatinine and β 2-microglobulin ( r=0.211, -0.142, 0.195, P<0.05). Conclusions:The plasma uranium concentration is significantly associated with the renal injury, which may provide epidemiology evidence for the prevention of renal injury.

Objective:To investigate the effect of visceral obesity on the short-term curative effect of Da Vinci robotic-assisted radical resec-tion for rectal cancers.Methods:Clinical and pathological data of patients with rectal cancer undergoing Da Vinci robotic-assisted surgery,admitted to People's Hospital of Zhengzhou University and Cancer Hospital of Zhengzhou University from November 2019 to June 2022 were retrospectively analyzed.Visceral fat area(VFA)≥100 cm2 was used as the standard to define visceral obesity.Patients were categorized in-to visceral and non-visceral obesity groups.The short-term efficacy of the two groups was evaluated,and the influencing factors of post-operative complications were analyzed using univariate and multivariate Logistic regression.Results:Among a total of 169 patients,93 were included in the visceral obesity group and 76 in the non-visceral obesity group.There was no significant difference in the baseline data between the two groups(P>0.05).There was no conversion to laparotomy in the non-visceral obesity group,and the conversion rate was 1.1%(1/93)in the visceral obesity group.The second operation rate was 2.2%(2/93)in the visceral obesity group and 1.3%(1/76)in the non-visceral obesity group with no statistical difference between the two groups.There were no significant differences in the operation dur-ation,intraoperative blood loss,number of lymph node dissections,and total postoperative complication rate between the two groups(P>0.05).Multivariate Logistic regression analysis revealed that an NRS≥3 independently contributed as a risk factor for postoperative com-plications(OR=3.190,95%CI:1.240-8.210,P=0.016).Conclusions:An NRS≥3 is an independent risk factor for complications post-robotic rad-ical rectal cancer surgery.The robotic surgical platform can overcome obesity-related limitations and is equally safe and effective for pa-tients with visceral obesity presenting with rectal cancer.

Background Exposure to uranium can result in multi-organ toxicity in humans. Some experimental studies have shown that uranium presents a damaging effect on liver, but no relevant population studies have been reported. Objective To investigate a potential association of plasma uranium exposure with liver injury. Methods The inhabitants of two representative areas of heavy metal pollution in northern and southern Hunan were selected as the research subjects. A total of 740 participants were recruited through 1∶1 paired case-control design based on a pre-determined diagnostic criterion for liver injury (defined as two or more anomalies among alanine aminotransferase, aspartate aminotransferase, and total bilirubin in the health examination) and the principle of case-control comparability. Information such as general demographic characteristics and medical history were collected through questionnaires and physical examination. Plasma uranium and liver function were determined by laboratory tests. Spearman correlation was applied to assess the association between plasma uranium concentration and liver injury indexes, and restricted cubic spline model was used to evaluate the dose-response relationship between plasma uranium concentration and liver injury. The participants were divided into four groups from Q1 to Q4 according to the quartile values of plasma uranium concentration of the control group after natural logarithmic transformation (with the Q1 group as the reference group), and the association between plasma uranium concentration and liver injury was evaluated by conditional logistic regression. Results The plasma uranium level in M (P₂₅, P₇₅) of the case group was 10.89 (6.78-18.53) ng·L⁻¹, higher than that in the control group, 9.26 (5.01-14.38) ng·L⁻¹ (P<0.001). The results of Spearman correlation analysis showed that alanine aminotransferase and aspartate aminotransferase were positively correlated with plasma uranium level (r_s=0.138, r_s=0.167; P<0.001). The restricted cubic spline model showed that the risk of liver injury increased with the increase of plasma uranium concentration (overall effect P<0.001). After adjusting for confounding factors such as gender, age, smoking, alcohol consumption, and prevalence of hypertension and hyperlipidemia, the results of conditional logistic regression analysis showed that the risks of liver injury in the Q2 group, the Q3 group, and the Q4 group were 2.043 (95%CI: 1.135-3.680), 2.246 (95%CI: 1.238-4.075), and 3.536 (95%CI: 1.955-6.397) times higher than that of the Q1 group respectively. Conclusion Plasma uranium exposure is associated with liver injury. This study is the first to provide population-level evidence of such an association.

OBJECTIVE：To stud y the effects of “green removing ”processing technology of fresh fruit of Schisandra chinensis after harvested on the quality of medicinal material ，and to provide new ideas for the scientific and rational processing of Chinese medicinal material. METHODS ：Fifteen fresh fruits of S. chinensis were used as samples ，with 3 samples in each group. The sample were processed preliminarily by 5 methods，such as drying at 50 ℃，drying in the sun ，drying at 50 ℃ after“green removing”processing with microwave ，drying at 50 ℃ after“green removing ”processing with blanching ，drying at 50 ℃ after “green removing ”processing with steaming. HPLC fingerprints of 15 batches of dried S. chinensis products were established and similarity evaluation was conducted according to Similarity Evaluation System of TCM Chromatographic Fingerprints （2012 edition）. Cluster analysis was used to evaluate the similarity of dried S. chinensis products with different processing methods. At the same time ，HPLC method was adopted to determine the content changes of seven lignans in dried products ，such as schisandrol A ， schisandrol B ，schisantherin A ，schisantherin B ，schizandrin A ，schisandrin B and schisandrin C. RESULTS ：A total of 7 common peaks were obtained in the fingerprints of 15 batches of dried S. chinensis products. Except that the similarity between the chromatograms of dried samples in the sun and the control fingerprint was relatively low ，the similarities of chromatograms of dried products by other processing methods were greater than 0.900. Cluster analysis showed that 6 samples dried at 50 ℃ after“green removing”processing with microwave and dried at 50 ℃ after“green removing ”processing with blanching were grouped into the first category ；3 samples dried at 50 ℃ after“green removing”processing with steaming were grouped into the second category ；6 samples dried at 50 ℃ and dried in sun were grouped into the third category. The content determination results showed that there was no significant difference in the total content of seven lignans in the samples dried at 50 ℃ and dried in the sun （P＞0.05）. The total contents of seven lignans in the samples dried at 50 ℃ after“green moving ” processing with microwave ，blanching and steaming were significantly higher than those dried at 50 ℃ and dried in sun （P＜0.01）. CONCLUSIONS：The quality of S. chinensis samples dried after “green moving ”processing with microwave and blanching is better than those directly dried in sun and dried in oven.

Objective:To report the clinical, electrophysiological and genetic features in a Chinese family with distal hereditary motor neuropathy type V (dHMN-V) and screen the pathogenic mutant gene.Methods:A family with the history of inherited peripheral neuropathy was recruited in the First Affiliated Hospital of Zhengzhou University in July 2017. The clinical features and electrophysiological data were investigated. Genetic testing on well-established genes associated with hereditary peripheral neuropathy was conducted by targeted high throughput sequencing and the candidate variant was screened in the family and normal controls.Results:There were four affected individuals in the family. The proband, a 25-year-old male, was characterized by weakness and atrophy in the distal extremities primarily affected the upper extremities without sensory impairment. Electrophysiological study showed chronic neurogenic pattern in the upper and lower limb muscles. The motor conduction showed reduced velocity and compound muscle action potential amplitude, while the sensory conduction studies results were normal. The grandfather, a maternal uncle and a cousin of the proband exhibited similar clinical manifestations and electrophysiological abnormality. Genetic testing revealed a heterozygous mutation, c.880G>A(p.G294R), in the GARS gene in the proband. Proband′s mother and two other affected individuals carried the mutation which was confirmed by Sanger sequencing. The mutation site was not found in the unaffected members from the family and 300 unrelated normal controls. The variant is a novel mutation which has not been reported in dbSNP, ExAC and 1000 Genomes Project databases. Conclusion:The results suggest that the novel c.880G>A(p.G294R) mutation of the GARS gene is responsible for the Chinese patients with dHMN-V, and the findings broaden the mutational spectrum of GARS gene.

With its high efficiency for site-specific genome editing and easy manipulation, the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 (CAS9) system has become the most widely used gene editing technology in biomedical research. In addition, significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases, several of which are entering clinical trials. Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA (gRNA) in human cells, promoting genomic DNA double-stranded break (DSB) damage and genomic instability. CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase (DNA-PK) complex and disrupts the interaction between KU86 and its kinase subunit, leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining (NHEJ) pathway. XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility, and dCAS9 is a CAS9 variant without nuclease activity. We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair. Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival, our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application.

Human embryonic stem cells (hESCs) depend on glycolysis for energy and substrates for biosynthesis. To understand the mechanisms governing the metabolism of hESCs, we investigated the transcriptional regulation of glucose transporter 1 (GLUT1, SLC2A1), a key glycolytic gene to maintain pluripotency. By combining the genome-wide data of binding sites of the core pluripotency factors (SOX2, OCT4, NANOG, denoted SON), chromosomal interaction and histone modification in hESCs, we identified a potential enhancer of the GLUT1 gene in hESCs, denoted GLUT1 enhancer (GE) element. GE interacts with the promoter of GLUT1, and the deletion of GE significantly reduces the expression of GLUT1, glucose uptake and glycolysis of hESCs, confirming that GE is an enhancer of GLUT1 in hESCs. In addition, the mutation of SON binding motifs within GE reduced the expression of GLUT1 as well as the interaction between GE and GLUT1 promoter, indicating that the binding of SON to GE is important for its activity. Therefore, SON promotes glucose uptake and glycolysis in hESCs by inducing GLUT1 expression through directly activating the enhancer of GLUT1.