Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

Peanut, a major economic and oil crop known for the high protein and oil content, is extensively cultivated in China. Peanut plants have the ability to form nodules with rhizobia, where the nitrogenase converts atmospheric nitrogen into ammonia nitrogen that can be utilized by the plants. Analysis of nodule fixation is of positive significance for avoiding overapplication of chemical fertilizer and developing sustainable agriculture. In this study, AhNIGT1.2, a member of the NIGT family predominantly expressed in peanut nodules, was identified by bioinformatics analysis. Subsequent spatiotemporal expression analysis revealed that AhNIGT1.2 was highly expressed in nodules and showed significant responses to high nitrogen, low nitrogen, high phosphorus, low phosphorus, and rhizobia treatments. Histochemical staining indicated that the gene was primarily expressed in developing nodules and at the connection region between mature nodules and peanut roots. The fusion protein AhNIGT1.2-GFP was located in the nucleus of tobacco epidermal cells. The AhNIGT1.2-OE significantly increased the number of peanut nodules, while AhNIGT1.2-RNAi reduced the number of nodules, which suggested a positive regulatory role of AhNIGT1.2 in peanut nodulation. The AhNIGT1.2-OE in roots down-regulated the expression levels of NRT1.2, NRT2.4, NLP1, and NLP7, which indicated that AhNIGT1.2 influenced peanut nodulation by modulating nitrate transport and the expression of NLP genes. The transcriptome analysis of AhNIGT1.2-OE and control roots revealed that overexpressing AhNIGT1.2 significantly enriched the differentially expressed genes associated with nitrate response, nodulation factor pathway, enzymes for triterpene biosynthesis, and carotenoid biosynthesis. These findings suggest that AhNIGT1.2 play a key role in peanut nodulation by regulating nitrate transport and response and other related pathways. This study gives insights into the molecular mechanisms of nitrogen and phosphorus in regulating legume nodulation and nitrogen fixation, and sheds light on the development of legume crops that can efficiently fix nitrogen in high nitrogen environments.
Arachis/physiology* ; Nitrates/metabolism* ; Plant Proteins/physiology* ; Transcription Factors/metabolism* ; Plant Root Nodulation/physiology* ; Gene Expression Regulation, Plant ; Root Nodules, Plant/metabolism* ; Nitrogen Fixation

Objective To construct a logistic regression prediction model for stress ulcer(SU)after cerebral hemorrhage.Methods A total of 230 patients with cerebral hemorrhage admitted to our hospital from January 2020 to January 2023 were prospectively selected as the study subjects.They were randomly di-vided into a training group and a validation group using a random number table method,with 115 patients in each group.The incidence of postoperative SU was statistically compared between the two groups.The least absolute shrinkage and selection operator(Lasso)and logistic regression were used to analyze the influencing factors of SU after cerebral hemorrhage,and a logistic regression prediction model was established and valida-ted.Results The incidence of SU was 19.13%in the training group and 20.00%in the validation group.In-crement of age,blood loss≥30 mL,higher levels of neutrophil-to-lymphocyte ratio(NLR),heat shock protein 70(HSP70)and HSP90 were identified as independent risk factors for SU after cerebral hemorrhage(P<0.05),while lower levels of Glasgow Coma Scale(GCS)score and albumin(Alb)were protective factors(P<0.05).The prediction model was logit(P)=0.409×age+1.288×blood loss-1.335×GCS score-1.126×Alb+0.452×NLR+1.483×HSP70+1.593×HSP90-10.325.The areas under the receiver operat-ing characteristic(ROC)curve(AUC)for the training group and the validation group were 0.845(95%CI:0.765-0.906)and 0.855(95%CI:0.777-0.913),respectively.The sensitivities were 81.82%and 90.91%,and the specificities were 76.34%and 70.97%,respectively.Conclusion A logistic regression prediction model was successfully constructed,which has certain predictive value for SU after cerebral hemorrhage.

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Alzheimer disease is a progressive neurodegenerative disorder which has emerged as a major public health concern with the global population aging, and the development of effective therapeutic agents has become increasingly urgent due to its rapid increase in prevalence. There is some progress in drug development, however, the majority of new drugs have failed to demonstrate sustained clinical efficacy in large-scale trials. In addition, high costs, severe side effects have further hindered the widespread application of these therapies. This article reviews recent progress in the development of pharmacological treatments for Alzheimer disease, focusing on disease-modifying therapies targeting amyloid-β and tau proteins, also analyzes the results of phase 2 and phase 3 clinical trials of traditional and novel drugs. Future research efforts should continue to explore novel therapeutic targets and strategies to offer more effective treatment options for patients with Alzheimer disease.

Objective To observe imaging manifestations of spinal chronic osteomyelitis.Methods Totally 56 patients with spinal chronic osteomyelitis were retrospectively enrolled,including 18 cases complicated with synovitis,acne,pustulosis,hyperostosis and osteomyelitis(SAPHO)syndrome while 38 cases did not.CT and MRI manifestations were observed.Results Among 56 cases,cervical spine involvement was observed in in 25 cases(25/56,44.64％).Single spine segment involvement,2 segments involvements and 3 or more segments involvements were found in 17(17/56,30.36％),18(18/56,32.14％)and 21 cases(21/56,37.50％),respectively.The ratio of 3 or more segments involvements in 18 cases with SAPHO syndrome was 61.11％(11/18),while in 38 cases without SAPHO syndrome was 26.32％(10/38),the former was higher than the latter(P＜0.05).Meanwhile,16 cases(16/56,28.57％)complicated with compression fracture,30(30/56,53.57％)with hyperosteogeny,22(22/56,39.29％)with paraspinal soft tissue swelled and 15(15/56,26.79％)with extra spinal involvements.The ratio of extra spinal involvement in patients with and without SAPHO syndrome was 72.22％(13/18)and 5.26％(2/38),respectively,the former was higher than the latter(P＜0.05).Conclusion Imaging manifestations of spinal chronic osteomyelitis had certain characteristics.In patients complicated with SAPHO syndrome,3 or more segments of spine involvements were common,with more extra spinal involvements.

BACKGROUND:The development of calcium phosphate bone cement is limited due to its poor mechanical properties and weak osteogenic ability.Silicate bioactive glass is highly favored due to its excellent biological activity and osteogenic ability.Simultaneously,fiber structures can enhance the mechanical strength of materials.OBJECTIVE:To investigate the mechanical properties,biocompatibility,and osteogenic effect of silicate bioactive glass fiber composite calcium phosphate bone cement.METHODS:Different mass percentages(0％,10％,and 20％)of silicate bioactive glass fiber were added to the solid phase of calcium phosphate bone cement,mixed with the liquid phase and cured for 48 hours to obtain silicate bioactive glass fiber composite calcium phosphate bone cement.The mechanical properties,setting time,and ion precipitation of the cement were characterized.The three groups of bone cement extracts were co-cultured with MC3T3-E1 cells.The cell compatibility of the materials was evaluated by CCK-8 assay,live/dead staining,and phalloidin staining.After osteogenic induction,the osteogenic induction ability of the materials was evaluated by alkaline phosphatase staining,alizarin red staining,RUNX2 immunofluorescence staining,and RT-PCR.RESULTS AND CONCLUSION:(1)With the increase of silicate bioactive glass fiber content,the compressive strength and flexural strength of bone cement increased,and the setting time was prolonged.When bone cement was immersed in simulated body fluid,the precipitation of silicon ions,calcium ions,and phosphorus ions could be detected.Moreover,with the increase of silicate bioactive glass fiber content,the mass concentration of silicon ions and phosphorus ions released by bone cement increased,and the mass concentration of calcium ions decreased.(2)Live/dead staining and phalloidin staining results exhibited that silicate bioactive glass fiber composite calcium phosphate bone cement had no toxic effect on MC3T3-E1 cells.CCK-8 assay results showed that silicate bioactive glass fiber composite calcium phosphate bone cement could promote the proliferation of MC3T3-E1 cells.(3)With the increase of silicate bioactive glass fiber content in bone cement,the alkaline phosphatase activity and extracellular calcium deposition of MC3T3-E1 cells increased,the expression of RUNX2 protein increased,and the expression of alkaline phosphatase,osteocalcin,osteopontin,and RUNX2 mRNA expression increased.(4)The results indicate that silicate bioactive glass fibers can enhance the mechanical properties and osteogenic induction ability of calcium phosphate bone cement,among which 20％silicate bioactive glass fibers have a more obvious effect.

Objective:To establish a reference interval for serum iodine of pregnant women with normal thyroid function and to analyze the relationship between serum iodine and thyroid disease risk.Methods:From July 2022 to October 2023, using cross-sectional survey method, pregnant women aged 18 to 48 years old who had lived in iodine-deficient areas in the six provinces of China (Shanxi Province, Fujian Province, Yunnan Province, Xinjiang Uygur Autonomous Region, Zhejiang Province, and Anhui Province) for more than six months were selected as the survey subjects. Blood samples were collected, serum iodine was tested, and the percentile method was used to establish a reference interval for serum iodine of pregnant women with normal thyroid function. Meanwhile, serum levels of free thyroxine, thyroid stimulating hormone, thyroglobulin antibody (TgAb), and thyroid peroxidase antibody (TPOAb) were tested, and logistic regression was used to analyze the relationship between serum iodine and thyroid disease risk.Results:A total of 1 409 pregnant women from 6 provinces were investigated, including 1 087 with normal thyroid function and 322 with abnormal thyroid function. The median serum iodine level of pregnant women with normal thyroid function was 79.74 μg/L, and the preliminary reference interval for serum iodine was 47.57 - 128.96 μg/L. When serum iodine levels were lower (< 47.57 μg/L), pregnant women had a significantly increased risk of developing TgAb positivity, TPOAb positivity, hypothyroxinemia, hypothyroidism, and autoimmune thyroiditis ( OR = 4.44, 2.91, 3.41, 41.67, 23.43, P < 0.05). When serum iodine levels were high (> 128.96 μg/L), pregnant women had a significantly increased risk of developing hyperthyroidism ( OR = 9.91, P = 0.001). Conclusions:The reference interval for serum iodine of pregnant women with normal thyroid function is successfully established. Low serum iodine levels are associated with an increased risk of TgAb positivity, TPOAb positivity, hypothyroxinemia, hypothyroidism, and autoimmune thyroiditis, while high serum iodine levels are associated with an increased risk of hyperthyroidism.

Objective:To analyze the clinical efficacy and learning curve for robot-assisted cortical bone trajectory (CBT) screw fixation performed by surgeons with different seniority in the treatment of lumbar degenerative disease.Methods:The clinical data of 91 lumbar degenerative disease patients underwent robot-assisted CBT screw fixation from August 2020 to December 2022 in Beijing Shijitan Hospital, Capital Medical University were retrospectively analyzed. Among them, 48 patients underwent surgery performed by the same senior surgeon (senior group), with a total of 234 CBT screws were placed; while 43 patients underwent surgery performed by the same junior surgeon (junior group), with a total of 206 CBT screws were placed. The surgical related indexes, functional improvement score, lower back pain and lower limb radiation pain scores, acceptable nail insertion rate, non invasion rate of facet joints and incidence of postoperative complications were compared between two groups. The functional improvement score was evaluated using the Japanese Orthopaedic Association (JOA) score, the pain score was evaluated using visual analog score (VAS). The cumulative sum (CUSUM) method was used to depict the learning curve with "single screw placement time" as the observation index.Results:There were no statistical difference in incision length, operation time, intraoperative blood loss and postoperative hospital stay between two groups ( P>0.05). The least squares means of JOA scores 1, 3 and 6 months after surgery in both groups increased significantly compared to baseline, while the least squares means of lower back pain VAS and lower limb radiation pain VAS decreased significantly compared to baseline; there were no statistical differences between two groups ( P>0.05). There were no statistical difference in acceptable nail insertion rate, non invasion rate of facet joints and incidence of postoperative complications between two group ( P>0.05). The CUSUM learning curves were fitting well and the inflection point for senior surgeon corresponded to 18 cases, while it was reached after performing surgery on 21 cases for junior surgeon. Conclusions:Robot-assisted CBT screw fixation performed by surgeons with different seniority could achieve similar clinical outcomes for treating lumbar degenerative disease. The senior surgeons are able to complete the initial learning stage faster than the junior surgeons, but there is not much difference in the number of surgeries performed the learning curve.