Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward.

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.

A Radical-Generating Probe to Release Free Fluorophores and Identify Artemisinin-Sensitive Cancer Cells.

The smart light-up probes have been extensively developed to image various enzymes and other bioactive molecules. Upon activation, these probes result in light-up fluorophores that exist in a protein-bound or a free form. The difference between these two forms has not yet been reported. Here, we present a pair of smart light-up probes that generate a protein-bound fluorophore and a free fluorophore upon activation by heme. Probe 8 generated a radical-attached fluorophore that predominantly existed in the free form, while probe 10 generated an α,ß-unsaturated ketone-attached fluorophore that showed extensive labeling of proteins. In live-cell imaging, probe 8 showed greater fluorescence intensity than probe 10 when low concentrations (0.1-5 µM) of the probes were used, but probe 8 was less fluorescent than probe 10 when the concentrations of the probes were high (10 µM). Finally, probe 8 was used to reflect the activation level of the endoperoxide bond in cancer cells and to effectively distinguish ART-sensitive cancer cells from ART-insensitive ones.

Association analysis between organophosphorus flame retardants exposure and the risk of depression: Data from NHANES 2017-2018.

BACKGROUND: Organophosphorus flame retardants (OPFRs) can damage the brain and may cause abnormal behaviors. There was no population-based study to reveal the relationship between OPFRs and the occurrence of depression. This study utilized a publicly available database to investigate the correlation between OPFRs exposure and the risk of depression, and the mediation effect of inflammation on the correlation. METHODS: Data in this study was from the database of the National Health and Nutrition Examination Survey. Multifactorial logistic regression was used to estimate the relationship between OPFRs exposure and the risk of depression, and a mediation effect model was constructed to explore the impact of inflammation on the correlation. RESULTS: Data of 1273 participants was included in the study. It was found that individuals with high urinary concentration of bis-(2-chloroethyl) phosphate had an increased risk of developing depression (OR = 1.217, 95 % CI: 1.032-1.435). Combined exposure to OPFRs was significantly associated with the increased risk of depression than single OPFRs exposure. Subgroup analyses based on inflammatory levels in the body revealed that inflammation might exert the mediation effect on the association between OPFRs exposure and the risk of depression, with the contribution proportion of 8.23 %. LIMITATIONS: Cross-sectional data and rapid metabolism of OPFRs lead to uncertainty in revealing long-term exposure in the body. CONCLUSIONS: There was a correlation between OPFRs exposure and the risk of depression, which may be mediated by inflammation in the body to some extent.

[Ligusticum cycloprolactam inhibits IL-1ß-induced apoptosis and inflammation of rat chondrocytes via HMGB1/TLR4/NF-κB signaling pathway].

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.

Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

The immune cell infiltration-associated molecular subtypes and gene signature predict prognosis for osteosarcoma patients.

Host immune dysregulation involves in the initiation and development of osteosarcoma (OS). However, the exact role of immune cells in OS remains unknown. We aimed to distinguish the molecular subtypes and establish a prognostic model in OS patients based on immunocyte infiltration. The gene expression profile and corresponding clinical feature of OS patients were obtained from TARGET and GSE21257 datasets. MCP-counter and univariate Cox regression analyses were applied to identify immune cell infiltration-related molecular subgroups. Functional enrichment analysis and immunocyte infiltration analysis were performed between two subgroups. Furthermore, Cox regression and LASSO analyses were performed to establish the prognostic model for the prediction of prognosis and metastasis in OS patients. The subgroup with low infiltration of monocytic lineage (ML) was related to bad prognosis in OS patients. 435 DEGs were screened between the two subgroups. Functional enrichment analysis revealed these DEGs were involved in immune- and inflammation-related pathways. Three important genes (including TERT, CCDC26, and IL2RA) were identified to establish the prognostic model. The risk model had good prognostic performance for the prediction of metastasis and overall survival in OS patients. A novel stratification system was established based on ML-related signature. The risk model could predict the metastasis and prognosis in OS patients. Our findings offered a novel sight for the prognosis and development of OS.

Computerised modified paramedian approach technique versus conventional midline approach technique of lumbar puncture: a randomised control trial protocol.

INTRODUCTION: The lumbar puncture (LP) technique is widely used for diagnostic and therapeutic purposes. In recent years, the paramedian approach technique (PAT) has gained increasing interest due to its advantages over the conventional midline approach technique (MAT) that has been traditionally employed in clinical practice for LP. However, there have been inconsistent discussions regarding the efficacy of different LP techniques. Based on digital virtual human and computer simulation techniques, a new approach called computerised modified PAT (CMPAT) was proposed. Therefore, the aim of this study is to discuss a randomised controlled trial (RCT) protocol to investigate and compare the effects of CMPAT and MAT in patients undergoing LP. METHODS AND ANALYSIS: We will conduct a prospective, multicentre RCT. The study will recruit 84 patients aged 18-99 years who require LP. Participants will be randomly assigned to either the CMPAT treatment group (group A) or the MAT treatment group (group B). The primary outcome measure will be the number of needle insertion attempts required for a successful LP. Secondary outcomes will include the puncture success rate, pain assessment in the back, head, and legs, and the occurrence of complications. The measurement of these secondary outcomes will be taken during the procedure, as well as at specific time points: 30 min, 6 hours, 1 day, 3 days, 7 days, 2 weeks and 4 weeks after the procedure. Pain levels will be assessed using a Numerical Rating Scale. ETHICS AND DISSEMINATION: Ethical approval (2022YF052-01) has been obtained from the Ethics Committee of Fujian Medical University Union Hospital, Fuzhou, China. The research findings will be published in an international peer-reviewed scientific journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300067937.

Analysis of the curative effect and prognostic factors in patients with scapular fracture with surgical indications after conservative treatment: a case series and clinical outcomes.

Background: The choice of treatment for scapular fractures is a topic worth discussing. The type of scapular fracture is often complex, and more and more scholars prefer surgical treatment to obtain better shoulder joint function. In addition, because of the rich blood supply and muscles of the scapula, some scholars believe that simple suspension can also achieve satisfactory clinical effects. The aim of this study was to investigate the curative effect and prognostic factors of patients with scapular fracture with indications for surgery after receiving conservative treatment. Methods: Patients with scapular fracture who did not receive surgical treatment from July 2016 to May 2021 were recruited from the orthopedic trauma database of Nanjing Gulou Hospital, and the data from patients with indications for surgery were screened out for a retrospective analysis. The data were obtained from the database of orthopaedic trauma patients in Nanjing Drum Tower Hospital. The relevant data were recorded during telephone and video follow-up visits. Linear regression was used to analyze the factors associated with disabilities of the arm, shoulder and hand (DASH) score after receiving conservative treatment. Results: A total of 21 patients were included in the final statistical analysis. All patients were followed up for 31.0±20.3 (range, 6-63) months, aged 52.9±12.7 (range, 27-71) years. All fractures had clinical healing with a 100% recovery satisfaction rate. Outcome measures of efficacy [both DASH scores and visual analogue scale (VAS) scores], were correlated with whether the fracture involved the superior border of the scapular, were not associated with the following variables: age (P=0.18), Injury Severity Score (ISS) score (P=0.10), the glenopolar angle (GPA) value (P=0.76), superior shoulder suspensory complex (SSSC) injury (P=0.82), and glenoid fracture (P=0.84). The range of motion of the affected shoulder was significantly reduced compared to the healthy shoulder (P<0.01), but the range of forward flexion and elevation was not significantly different from that of the healthy shoulder (P>0.05). Patients with fractures not involving the superior border of the scapula had a much lower range of motion in the affected shoulder than in the healthy shoulder during abduction (P<0.05). Conclusions: The range of surgical indications for scapular fractures with scapular fractures involving the lower margin of the scapular can be appropriately narrowed. Some patients with scapular fracture who have surgical indications can regain satisfactory shoulder function after receiving conservative treatment.

Sublethal effects of emamectin benzoate on development, reproduction, and vitellogenin and vitellogenin receptor gene expression in Thrips hawaiiensis (Thysanoptera: Thripidae).

Thrips hawaiiensis (Morgan) (Thysanoptera: Thripidae) is a sap-sucking pest that seriously damages several crops and reduces their economic value. Exposure to low concentrations of insecticides may have a sublethal effect on surviving insects. In order to provide a reference for the rational application of emamectin benzoate, its sublethal effects on the development and reproduction of T. hawaiiensis were evaluated. Pupal development time was significantly shorter in T. hawaiiensis treated with sublethal concentrations of emamectin benzoate (LC10 and LC20) than in control. Female adult longevity and female total longevity were significantly longer following LC20 treatment than in the control and LC10 treatment groups. Nevertheless, male adult longevity and male total longevity were significantly shorter in the LC10 treatment group than in the control and LC20 treatment groups. The sublethal concentration of emamectin benzoate (LC20) significantly shortened the preadult stages and the mean generation. Meanwhile, it significantly increased the finite rate of increase, intrinsic rate of increase, and net reproductive rate. The fecundity was significantly higher after LC20 treatment than after LC10 and control treatments. Compared with the control group, the LC10 and LC20 groups of T. hawaiiensis adults showed a significantly higher expression of the vitellogenin (Vg) and vitellogenin receptor (VgR) genes, which played a key role in increasing their fecundity. These findings suggest that short-term exposure to sublethal concentrations of emamectin benzoate may lead to a resurgence and secondary outbreak of T. hawaiiensis infestation. The results have practical applications for the management of this important and noxious pest.

Successful treatment of disseminated nocardiosis diagnosed by metagenomic next-generation sequencing: A case report and review of literature.

BACKGROUND: Nocardia paucivorans is an infrequently found bacterium with the potential to cause severe infection, with a predilection for the central nervous system, both in immunocompromised and immunocompetent individuals. Rapid etiological diagnosis of nocardiosis can facilitate timely and rational antimicrobial treatment. Metagenomic next-generation sequencing (mNGS) can improve the rate and reduce the turnaround time for the detection of Nocardia. CASE SUMMARY: A 49-year-old man was admitted to hospital with cough and hemoptysis. Imaging revealed pulmonary consolidation as well as multiple brain lesions. Nocardia asiatica and Nocardia beijingensis were rapidly detected by mNGS of bronchoalveolar lavage fluid (BALF) while bacterial culture of BALF and pathological biopsy of lung tissue were negative. In early stages, he was treated with trimethoprim-sulfamethoxazole (TMP-SMZ) and linezolid by individual dose adjustment based on serum concentrations and the adverse effects of thrombocytopenia and leukopenia. The treatment was then replaced by TMP-SMZ and ceftriaxone or minocycline. He was treated with 8 mo of parenteral and/or oral antibiotics, and obvious clinical improvement was achieved with resolution of pulmonary and brain lesions on repeat imaging. CONCLUSION: mNGS provided fast and precise pathogen detection of Nocardia. In disseminated nocardiosis, linezolid is an important alternative that can give a better outcome with the monitoring of linezolid serum concentrations and platelet count.

[Analysis of risk factors of multiple fractures of limbs complicated with pleural effusion].

OBJECTIVE: To explore the risk factors of limb fracture complicated with pleural effusion, and to provide reference for the prevention of pleural effusion. METHODS: From January 2010 to December 2019, 137 patients with multiple limb fractures were treated surgically, including 102 males and 35 females, aged 16 to 92(48.34±15.85) years. Multiple limb fractures were defined as more than two limb fractures in the whole body, so the selected patients had complete clinical, impact and laboratory examination data before operation, including preoperative chest CT, gender, age, body mass index(BMI), hematocrit(HCT), American Society of Anesthesiologists(ASA), injury severity score (ISS), smoking history of operation, history of diabetes, history of hypertension, admission to operation time, fracture site, platelet count, albumin, C-reactive protein and D-dimer. Whether the patient was complicated with pleural effusion, calculate the amount of pleural effusion were recorded, and the relevant risk factors were statistically analyzed. RESULTS: All limb fractures received surgical treatment. The incision healed well after operation, and there were no complications such as wound infection, acute lung injury or acute respiratory distress syndrome. Multivariate regression analysis showed that ISS higher than 16(P=0.000), smoking history(P=0.001) and rib fracture(P=0.000) were the risk factors of multiple limb fractures complicated with pleural effusion. Multivariate linear regression analysis showed that smoking history, ISS and rib fracture were the risk factors for the increase of pleural effusion in multiple limb fractures. CONCLUSION: Multiple fractures of limbs combined with pleural effusion are related to ISS, smoking history and rib fracture;the amount of pleural effusion was related to smoking history, ISS and rib fracture. Patients with multiple fractures with ISS greater than 16, smoking history or rib fracture should be vigilant and intervene as soon as possible to reduce the risk of pleural effusion.

[Using the environmental justice approach to evaluate equitable allocation of urban parks: A case study of main urban area of Nanjing, China]. / çŽ¯å¢ƒæ­£ä¹‰è§†è§’ä¸‹å ¬å›­ç»¿åœ°ç©ºé—´é ç½®å ¬å¹³æ€§è¯„ä»·­­ä»¥å—京市主城区为例.

Urban parks have broad benefits in promoting public health of urban residents and advancing urban sustainable development. The equity of urban park spatial allocation has a great significance for maintaining environmental justice. However, the current researches on the equity of urban park spatial allocation still focus on the quantity and geographical equality but pay less attention on the equity of quality and accessibility of spatial allocation. Based on the approach of environmental justice, with the main urban area of Nanjing as an example, we comprehensively analyzed the equity pattern of urban park spatial allocation from the three dimensions (six parameters), including park accessibility, area and quality. Integrated analysis methods were adopted, including internet map service for accessibility analysis, subjective and objective comprehensive quality evaluation, spatial autocorrelation and non-parametric test. The results showed that the spatial allocation pattern of urban parks in the study area had obvious core-edge characteristics. There was a certain degree of inequity in park accessibility, area and quality, with a relatively significant pattern of environmental injustice. There were significant differences in the inequity of six parameters in the three dimensions, with the accessibility score and accessible park area showing the most prominent inequity. The minimum time required to reach the park and the quality of the nearest urban park took the second place in inequity. The quantity of high-quality urban park and minimum time required to reach the high-quality urban park showed relatively small difference. The average values of accessibility score, total area and quality of urban parks accessible to high-income communities were 3.7, 2.7, and 1.6 times that of low-income communities, respectively. The results indicated that high-income communities enjoyed better accessibility, larger area and higher quality in terms of urban parks. Middle-income communities enjoyed the most prominent advantage of green space, while most low-income communities were unable to reach a high-quality urban park within 30 min's walk. Our results could provide a decision-making basis and planning reference for the optimal configuration and rational planning of urban parks in China.

Sodium selenite promotes neurological function recovery after spinal cord injury by inhibiting ferroptosis.

Ferroptosis is a recently discovered form of iron-dependent cell death, which occurs during the pathological process of various central nervous system diseases or injuries, including secondary spinal cord injury. Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis. However, whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood. In this study, we injected sodium selenite (3 µL, 2.5 µM) into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling. We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Furthermore, sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4, promoted the survival of neurons and oligodendrocytes, inhibited the proliferation of astrocytes, and promoted the recovery of locomotive function of rats with spinal cord injury. These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.

Diagnostic value of platelet indices in infected nonunion: a retrospective study.

BACKGROUND: The diagnostic value of platelet indices has been evaluated in various infectious diseases but not in infected nonunion. The purpose of this study was to assess the usefulness of platelet indices for diagnosis of infected nonunion after open reduction and internal fixation. METHODS: This retrospective study was performed in patients who underwent primary fracture nonunion revision surgeries from January 2016 to December 2021. A total of 297 patients were included in the study: 96 with infected nonunion (group A) and 201 with aseptic nonunion (group B). Receiver operator characteristic (ROC) curve analysis was performed to evaluate diagnostic value of each index. Area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated and compared. RESULTS: Demographic characteristics were comparable between the two groups. White blood cell (WBC) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen, plasma D-dimer, platelet count (PC), plateletcrit, and ratio of platelet count to mean platelet volume (PC/MPV) were significantly higher, and MPV and platelet distribution width (PDW) significantly lower, in group A than in group B (P < 0.05). ROC analysis showed PC/MPV and plasma fibrinogen to have better diagnostic value than the other coagulation indicators (AUC of 0.801 and 0.807, respectively). The combination of ESR, plasma fibrinogen, and PC/MPV had good sensitivity and specificity for diagnosis of infected nonunion. PC/MPV had better diagnostic value than ESR and plasma fibrinogen in the subgroup of patients with coagulation-related comorbidities. CONCLUSIONS: Plasma fibrinogen and PC/MPV ratio might be useful parameters for early diagnosis of infected nonunion.

Autophagy and Diabetic Encephalopathy: Mechanistic Insights and Potential Therapeutic Implications.

Diabetic Encephalopathy (DE) is one of the complications of diabetes mellitus (DM) in the central nervous system. Up to now, the mechanisms of DE are not fully discussed by the field. Autophagy is an intracellular degradation pathway crucial to maintain cellular homeostasis by clearing damaged organelles, pathogens, and unwanted protein aggregates. Increasing evidence has demonstrated that autophagy might play an essential role in DE progress. In this review, we summarize the current evidence on autophagy dysfunction under the condition of DE, and provide novel insights of possibly biological mechanisms linking autophagy impairment to DE, as well as discuss autophagy-targeted therapies as potential treatments for DE.