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Atopic dermatitis (AD) is a chronic and inflammatory skin disorder characterized by impaired barrier function and imbalanced immunity. Recent advances have revealed that dysbiosis of skin microbiota plays important roles in the pathogenesis and development of AD. Meanwhile, endogenous and external factors contribute to the dysbiosis of skin microbiota in AD. Additionally, various treatments, including topical treatments, phototherapy, and systemic biologics, have demonstrated positive impacts on the clinical outcomes, alongside with the modulations of cutaneous microbiota in AD patients. Importantly, therapeutics or products regulating skin microbiota homeostasis have demonstrated potential for AD treatment in early clinical studies. In this review, we underline changes of the skin microbiota correlated with AD. Meanwhile, we provide an overview of the skin microbiota regarding its roles in the pathogenesis and development of AD. Finally, we summarize therapeutic strategies restoring the skin microbial homeostasis in AD management.

Objectives To investigate the clinical epidemiological characteristics and occurrence of post-traumatic stress symptoms (PTSS) in patients with traumatic fractures, we sought to analyze the factors that influence the prognosis of a length of hospital stay (LOS) and provide valuable insights to prevent PTSS in fracture patients and improve their prognosis. Methods Inpatients with traumatic fractures were recruited from a third-class comprehensive general hospital in southwest China between November 2019 and October 2020. Case data of traumatic fracture patients were collected, and a questionnaire that included general information and basic fracture details was completed. The post-traumatic stress disorder Self-rating Scale was used to assess PTSS among the fracture inpatients. Results A total of 204 inpatients who experienced traumatic fractures were included in this study. Falls accounted for the largest proportion of traumatic fractures. A Cox's regression analysis revealed that serious injury [Hazard Ratio (HR) = 2.44, 95% Confidence Interval (CI): 1.33–4.46], critical illness during hospitalization (HR = 1.70, 95% CI: 1.13–2.54), and undergoing two surgeries (HR = 1.87, 95% CI: 1.20–2.93) were risk factors for longer LOS. Among the fracture patients, 30.39% exhibited positive PTSD symptoms, and physical activity during the fracture [Odds Ratio (OR) = 0.63, 95% CI: 0.45–0.88] and increased pain (OR = 3.34, 95% CI: 1.82–6.11) were identified as influencing factors. Conclusions Given the high detection rate of PTSS following traumatic fractures, it is crucial for relevant departments to implement targeted measures to protect high risk individuals. Furthermore, strengthening the care provided to the patients' physical and mental health is urgently needed to reduce the incidence of PTSS.

Background Road traffic injuries (RTIs) are a serious global problem, and a huge challenge for both economic development and public health. Methods This longitudinal study was based on the national data from Chinese authorities. Descriptive analysis was utilized to analyze the prevalence and trend of RTIs among different types, groups and regions. In addition, ridge regression or/and curve regression were also used to explore the relationship between those possible influencing factors and RTIs. Results From 2010 to 2019, the death toll from motor vehicle accidents (MVAs) decreased firstly and then increased, while the death toll from non-MVAs continued to rise since 2012, and the death toll from pedestrian and occupant accidents fluctuated only a little. The mortality rate of MVA was relatively stable from 2010 to 2012, and declined from 2013. The mortality rate of motor vehicle accidents was higher in rural than urban, the same to male compared with female. The results of ridge regression showed that gross domestic product (GDP)-per-capita, total population, number of health personnel and car ownership were positively correlated with the death toll of non-MVAs (P < 0.05). Additionally, the results of curve regression suggested that the quadratic or cubic relationship between each factor and the number of MVAs was well fitted, while only partially fitted in fatalities. Conclusions In recent years, RTIs in China show different trends, and the problem of non-motor vehicle traffic injuries has been neglected which should be paid more attention. Moreover, according to the new trends and traffic conditions in RTIs revealed in this study, it is necessary to formulate targeted intervention measures establish a multi-faceted comprehensive safety system to reduce the disease burden of RTIs as well as the total injuries.

Copper/zinc superoxide dismutase (Cu/Zn-SOD) plays critical roles in protecting cells and tissues against oxidative damage. Excessive copper ions (Cu2+) in water can damage the cells of aquatic organisms, leading to impaired growth and development and reduced antioxidant defenses. Many regulatory factors control the response to excess Cu2+. Among them, microRNAs (miRNAs) are important small RNAs that regulate the expression of their target genes and participate in the oxidative stress response. In the present study, we used bioinformatics and dual luciferase reporter gene analyses to demonstrate that the miR-489-3p of hybrid yellow catfish (Pelteobagrus fulvidraco♀ × P. vachelli♂) binds to the 3′-untranslated region (UTR) of its target gene, which encodes a Cu/Zn-SOD. The regulatory relationship between this miRNA and its target gene Cu/Zn-SOD was analyzed using qRT-PCR and luciferase activity assays. We also investigated the effect of the loss of miR-489-3p expression on the oxidative stress response of hybrid yellow catfish exposed to Cu2+. The Cu/Zn-SOD 3′UTR region was found to be fully complementary to positions 2–9 of the 5′-end seed region of miR-489-3p. The miR-489-3p expression levels were negatively related to Cu/Zn-SOD expression. Silencing of miR-489-3p up-regulated Cu/Zn-SOD expression in the liver and gill tissues, increased activities of SOD and catalase, and reduced the malondialdehyde content. This study is the first to demonstrate that miR-489-3p targets Cu/Zn-SOD to mediate the oxidative response to metal stress. These findings provide a theoretical basis for further studies on the response to oxidative stress caused by metals in cultured fish, and provide an experimental basis for the management of the culture environment.

Abstract Osteoporotic fractures impose a substantial burden on patients with diabetes due to their unique characteristics in bone metabolism, limiting the efficacy of conventional fracture prediction tools. Artificial intelligence (AI) algorithms have shown great promise in predicting osteoporotic fractures. This review aims to evaluate the application of traditional fracture prediction tools (FRAX, QFracture, and Garvan FRC) in patients with diabetes and osteoporosis, review AI-based fracture prediction achievements, and assess the potential efficiency of AI algorithms in this population. This comprehensive literature search was conducted in Pubmed and Web of Science. We found that conventional prediction tools exhibit limited accuracy in predicting fractures in patients with diabetes and osteoporosis due to their distinct bone metabolism characteristics. Conversely, AI algorithms show remarkable potential in enhancing predictive precision and improving patient outcomes. However, the utilization of AI algorithms for predicting osteoporotic fractures in diabetic patients is still in its nascent phase, further research is required to validate their efficacy and assess the potential advantages of their application in clinical practice.

Objective. A burn is an inflammatory injury to the skin or other tissue due to contact with thermal, radioactive, electric, or chemical agents. Burn injury is an important cause of disability and death worldwide. Obesity is a significant public health problem, often causing underlying systemic inflammation. Studying the combined impact of burn injuries on obese patients has become critical to the successful treatment of these patients. The aim of this paper is to highlight the effect of inflammation associated with burn injuries on several body weight group in a rat study. Materials and methods. Different degrees of obesity and burns were established in rats and divided into a normal weight group, overweight group, obese group, second-degree burn group, third-degree burn group, over-weight second-degree burn group, over-weight third-degree burn group, obese second-degree burn group, and obese third-degree burn group (20 rats per group). Changes in inflammatory factors and growth factor were measured on the 1st, 3rd, 7th and 14th days after burns were inflicted. Results. The ELISA test showed that in the unburned control group, MCP-1, IL-1β and TNF-α protein expressions in the obese and over-weight groups were higher than the normal-weight group (P < 0:05). RT-PCR test showed that the expressions of MCP-1, IL-1β and TNF-α genes in the obese group were higher compared to the overweight and normal weight groups (P < 0:05). Three and 7 days after burns were inflicted, the level of VEGF in the normal weight group was higher than the obese group (P < 0:05), however increased VEGF was not observed on days 1 and 14. Conclusion. Burn injury and obesity have a mutually synergistic effect on the body's inflammatory response. [ABSTRACT FROM AUTHOR]

Acquired resistance to cyclin-dependent kinases 4 and 6 (CDK4/6) inhibition in estrogen receptor-positive (ER+) breast cancer remains a significant clinical challenge. Efforts to uncover the mechanisms underlying resistance are needed to establish clinically actionable targets effective against resistant tumors. In this study, we sought to identify differentially expressed genes (DEGs) associated with acquired resistance to palbociclib in ER+ breast cancer. We performed next-generation transcriptomic RNA sequencing (RNA-seq) and pathway analysis in ER+ MCF7 palbociclib-sensitive (MCF7/pS) and MCF7 palbociclib-resistant (MCF7/pR) cells. We identified 2183 up-regulated and 1548 down-regulated transcripts in MCF7/pR compared to MCF7/pS cells. Functional analysis of the DEGs using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database identified several pathways associated with breast cancer, including ‘cell cycle’, ‘DNA replication’, ‘DNA repair’ and ‘autophagy’. Additionally, Ingenuity Pathway Analysis (IPA) revealed that resistance to palbociclib is closely associated with deregulation of several key canonical and metabolic pathways. Further studies are needed to determine the utility of these DEGs and pathways as therapeutics targets against ER+ palbociclib-resistant breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Background and objectives Research suggests that diabetic peripheral neuropathy (DPN) is related to plasma fibrinogen (Fib) concentrations, although its correlation with Fib function has not been reported. Here, the k value and angle α, reflecting the plasma Fib function, were used to analyse its correlation with DPN, and their potential as biological indicators for diagnosing DPN was explored. Subjects and methods This prospective observational clinical study enrolled 561 type 2 diabetes mellitus (T2DM) patients, who were divided into the diabetes with symptomatic neuropathy (161 cases), diabetes with asymptomatic neuropathy (132 cases) and diabetes with no neuropathy (268 cases) groups. Meanwhile, 160 healthy unrelated subjects were recruited as controls. Results Fib levels increased slightly in diabetic subjects with neuropathy compared with those without. The angle α levels increased slightly in subjects with asymptomatic DPN compared with those with no neuropathy and increased greatly in subjects with symptomatic DPN compared with those without. The k value levels slightly decreased in subjects with asymptomatic DPN compared with those with no neuropathy and greatly decreased in subjects with symptomatic DPN compared with those without. The association of the k value and angle α with diabetic neuropathy was independent of the hyperglycaemic state and other potential confounders (odds ratio 0.080 [0.051–0.124], P

ObjectiveTo investigate the value of the retinal nerve fiber layer (RNFL) thickness in the optic disc and the cross-sectional area (CSA) of lower limb nerves in the diagnosis of diabetic peripheral neuropathy (DPN) separately and in combination.MethodsA total of 140 patients with type 2 diabetes were enrolled, including 51 patients with DPN (DPN group) and 89 patients without DPN (NDPN group). Clinical data and biochemical parameters were collected. Electromyography/evoked potential instrument was performed for nerve conduction study. Optical coherence tomography was performed to measure the RNFL thickness of the optic disc. Color Doppler ultrasound was performed to measure CSA of lower limb nerves.ResultsThe RNFL thickness was lower and the CSA of the tibial nerve (TN) in the DPN group was larger than that in the NDPN group. The album/urine creatinine ratio, diabetic retinopathy, and CSA of TN at 3 cm were positively correlated with DPN. The RNFL thickness in the superior quadrant of the optic disc was negatively correlated with DPN. For RNFL thickness to diagnose DPN, the area under the curve (AUC) of the superior quadrant was the largest, which was 0.723 (95% confidence interval [CI]: 0.645–0.805), and the best cutoff value was 127.5 μm (70.5% sensitivity, 72.1% specificity). For CSA of TN to diagnose DPN, the AUC of the distance of 5 cm was the largest, which was 0.660 (95% CI: 0.575–0.739), and the best cutoff value was 13.50 mm2 (82.0% sensitivity, 41.6% specificity). For the combined index, the AUC was greater than that of the above two indicators, which was 0.755 (95% CI: 0.664–0.846), and the best cutoff value was 0.376 (64.3% sensitivity, 83.0% specificity).ConclusionsPatients with DPN have a reduction of the RNFL thickness and an increase in the CSA of TN, and these two changes are related to DPN. The RNFL thickness of the optic disc and the CSA of TN can be used as diagnostic indicators of DPN, and the combination of the two indicators has a higher diagnostic value.

Through the past decade of research, the pathogenic mechanisms underlying metabolic syndrome have been suggested to involve not only the peripheral tissues, but also central metabolic regulation imbalances. The hypothalamus, and the arcuate nucleus in particular, is the control center for metabolic homeostasis and energy balance. Neuropeptide Y neurons are particularly abundantly expressed in the arcuate of the hypothalamus, where the blood-brain barrier is weak, such as to critically integrate peripheral metabolic signals with the brain center. Herein, focusing on metabolic syndrome, this manuscript aims to provide an overview of the regulatory effects of Neuropeptide Y on metabolic syndrome and discuss clinical intervention strategy perspectives for neurometabolic disease.

Acute kidney injury (AKI) is one of the most severe consequences of kidney injury, and it will also cause or aggravate the complications by the fast decline of kidney excretory function. Accurate AKI prediction, including the AKI case, AKI stage, and AKI onset time interval, can provide adequate support for effective interventions. Besides, discovering how the medical features affect the AKI result may also provide supporting information for disease treatment. An attention-based temporal neural network approach was employed in this study for AKI prediction and for the analysis of the impact of medical features from temporal electronic health record (EHR) data of patients before AKI diagnosis. We used the publicly available dataset provided by the Medical Information Mart for Intensive Care (MIMIC) for model training, validation, and testing, and then the model was applied in clinical practice. The improvement of AKI case prediction is around 5% AUC (area under the receiver operating characteristic curve), and the AUC value of AKI stage prediction on AKI stage 3 is over 82%. We also analyzed the data by two steps: the associations between the medical features and the AKI case (positive or inverse) and the extent of the impact of medical features on AKI prediction result. It shows that features, such as lactate, glucose, creatinine, blood urea nitrogen (BUN), prothrombin time (PT), and partial thromboplastin time (PTT), are positively associated with the AKI case, while there are inverse associations between the AKI case and features such as platelet, hemoglobin, hematocrit, urine, and international normalized ratio (INR). The laboratory test features such as urine, glucose, creatinine, sodium, and blood urea nitrogen and the medication features such as nonsteroidal anti-inflammatory drugs, agents acting on the renin–angiotensin system, and lipid-lowering medication were detected to have higher weights than other features in the proposed model, which may imply that these features have a great impact on the AKI case.

Microglia are critical in neuroinflammation. M1/M2 polarization transitions of microglial phenotypes determine the states of neuroinflammation and are regulated by multiple pathways, including miRNAs and other epigenetic regulations. This study investigated the polarization transitions of microglia induced by high glucose and glucose fluctuations, and the role of miR-146a in regulating M1/M2 polarization transitions of microglia. BV-2 cells were cultured with 25 mmol/L glucose, 75 mmol/L glucose, and 25 mmol/L−75 mmol/L glucose fluctuation for 48 h. BV-2 cells overexpressing miR-146a were generated using a lentiviral vector. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure mRNA expression of miR-146a, CD11b, iNOS, Arg-1, IRAK1, TRAF6, and NF-κB. Immunofluorescence was used to measure CD11b expression. Western blot was used to measure protein expression of CD11b, iNOS, and Arg-1. Compared with those in the 25 mmol/L glucose control group, expression of CD11b, iNOS, TNF-α, and IL-6 in the 75 mmol/L glucose or glucose fluctuation groups of cultured BV-2 cells were significantly increased, while Arg-1 and IL-10 was significantly decreased. These effects were reversed by overexpression of miR-146a. Furthermore, expression of IRAK1, TRAF6, and NF-κB was significantly increased in the high glucose and glucose fluctuation groups; this was reduced after miR-146a overexpression. In sum, high glucose and glucose fluctuations induced polarization transitions from M1 to M2 phenotype in BV-2 cells. Overexpression of miR-146a might protect BV-2 cells from high glucose and glucose fluctuation associated with M1/M2 polarization transitions by downregulating the expression of IRAK1, TRAF6, and NF-κB.

Background: Diabetic nephropathy (DN) is the leading cause of end-stage failure of the kidneys; however, its pathogenesis remains unknown. This study assessed the expression of complement components in the kidneys of rats with type 2 DN to investigate their role in DN.Methods: A rat model of type 2 DN was induced by a high-fat diet combined with low-dose streptozotocin. Blood glucose, fasting insulin levels, insulin resistance index, and 24-h urinary albumin excretion (UAE) were measured. Renal tissue morphological features were observed. The mesangial index and arteriosclerosis index were calculated. Immunohistochemistry and western blot were used to measure the expression of complement components in the kidneys.Results: The kidney weight: body weight (mg/g) ratio in the DN group was significantly greater than those in the control and diabetes mellitus (DM) groups. The arteriosclerosis index, mesangial index, and tube area percentage in the DN group were significantly higher than those in the control and DM groups, but these parameters did not significantly differ between the control and DM groups. The expression of the complement components C1q, mannose-binding lectin (MBL), mannan-binding lectin-associated serine protease (MASP)-2, B factor, C3, and C5b-9 in the DN group was significantly higher than that in the control and DM groups but did not significantly differ between the control and DM groups. Most of the complement components were mainly expressed at the renal tubular site. Correlation analysis showed that 24-h UAE were positively correlated with C1q, MBL, MASP-2, B factor, and C5b-9 expression. MI was positively correlated with MBL, B factor, C3, and C5b-9 expression. AI was positively correlated with C1q, MBL, MASP-2, and B factor expression.Conclusion: Complement components including C1q, MBL, MASP-2, B factor, C3, and C5b-9, were highly expressed in the kidneys of type 2 diabetic rats with DN. Most of the complement components were mainly expressed in the renal tubules. High expression of complement components was found to be associated with the progress of DN. Our study suggests that complement system activation is a progressive factor in type 2 diabetic nephropathy. Inhibition of pathological complement activation may be a promising therapeutic strategy for DN.