Microbiological profile of diabetic foot infections in China and worldwide: a 20-year systematic review.

Introduction: Pathogens causing diabetic foot infections (DFIs) vary by region globally; however, knowledge of the causative organism is essential for effective empirical treatment. We aimed to determine the incidence and antibiotic susceptibility of DFI pathogens worldwide, focusing on Asia and China. Methods: Through a comprehensive literature search, we identified published studies on organisms isolated from DFI wounds from January 2000 to December 2020. Results: Based on our inclusion criteria, we analyzed 245 studies that cumulatively reported 38,744 patients and 41,427 isolated microorganisms. DFI pathogens varied according to time and region. Over time, the incidence of Gram-positive and Gram-negative aerobic bacteria have decreased and increased, respectively. America and Asia have the highest (62.74%) and lowest (44.82%) incidence of Gram-negative bacteria, respectively. Africa has the highest incidence (26.90%) of methicillin-resistant Staphylococcus aureus. Asia has the highest incidence (49.36%) of Gram-negative aerobic bacteria with species infection rates as follows: Escherichia coli, 10.77%; Enterobacter spp., 3.95%; and Pseudomonas aeruginosa, 11.08%, with higher local rates in China and Southeast Asia. Linezolid, vancomycin, and teicoplanin were the most active agents against Gram-positive aerobes, while imipenem and cefoperazone-sulbactam were the most active agents against Gram-negative aerobes. Discussion: This systematic review showed that over 20 years, the pathogens causing DFIs varied considerably over time and region. This data may inform local clinical guidelines on empirical antibiotic therapy for DFI in China and globally. Regular large-scale epidemiological studies are necessary to identify trends in DFI pathogenic bacteria. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447645.

Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Chronic osteomyelitis risk is associated with NLRP3 gene rs10754558 polymorphism in a Chinese Han Population.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the nucleotide-binding domain leucine-rich repeat protein-3 (NLRP3) gene are reported to be linked to many inflammatory disorders. However, uncertainty persists over the associations between these SNPs and susceptibilities to chronic osteomyelitis (COM). This study aimed to investigate potential relationships between NLRP3 gene SNPs and the risks of developing COM in a Chinese Han cohort. METHODS: The four tag SNPs of the NLRP3 gene were genotyped in a total of 428 COM patients and 368 healthy controlsusing the SNapShot technique. The genotype distribution, mutant allele frequency, and the four genetic models (dominant, recessive, homozygous, and heterozygous) of the four SNPs were compared between the two groups. RESULTS: A significant association was found between rs10754558 polymorphism and the probability of COM occurence by the heterozygous model (P = 0.037, odds ratio [OR] = 1.541, 95% confidence interval [CI] = 1.025-2.319), indicating that rs10754558 may be associated with a higher risk of developing COM.In addition, possible relationship was found between rs7525979 polymorphism and the risk of COM development by the outcomes of homozygous (P = 0.073, OR = 0.453, 95% CI = 0.187-1.097) and recessive (P = 0.093, OR = 0.478, 95% CI = 0.198-1.151) models, though no statistical differences were obtained. CONCLUSIONS: Outcomes of the present study showed, for the first time, that rs10754558 polymorphism of the NLRP3 gene may increase the risk of COM development in this Chinese Han population, with genotype CG as a risk factor. Nonetheless, this conclusion requires verification from further studies with a larger sample size.

MicroRNA-18a regulates the Pyroptosis, Apoptosis, and Necroptosis (PANoptosis) of osteoblasts induced by tumor necrosis factor-α via hypoxia-inducible factor-1α.

BACKGROUND: Tumor necrosis factor-α (TNF-α) is involved in inflammatory responses and promotes cell death and the inhibition of osteogenic differentiation. MicroRNA (miRNA) plays a crucial role in the infected bone diseases, however, the biological role of miRNAs in inflammation-induced impaired osteogenic differentiation remains unclear. This study aimed to explore the role of miRNA-18a-5p (miR-18a) in regulating PANoptosis and osteogenic differentiation in an inflammatory environment via hypoxia-inducible factor-1α (HIF1-α). METHODS: The expression of miR-18a in MC3T3-E1 cells was analyzed using quantitative reverse transcription-polymerase chain reaction in an inflammatory environment induced by TNF-α. The expression of HIF1-α and NLRP3 in LV-miR-18a or sh-miR-18a cells was analyzed using western blotting. Fluorescence imaging for cell death, flow cytometry, and alkaline phosphatase activity analysis were used to analyze the role of miR-18a in TNF-α-induced PANoptosis and the inhibition of osteogenic differentiation. An animal model of infectious bone defect was established to validate the regulatory role of miR-18a in an inflammatory environment. RESULTS: The expression of miRNA-18a in the MC3T3-E1 cell line was significantly lower under TNF-α stimulation than in the normal environment. miR-18a significantly inhibited the expression of HIF1-α and NLRP3, and inhibition of HIF1-α expression further inhibited NLRP3 expression. Furthermore, inhibition of miR-18a expression promoted the TNF-α-induced PANoptosis and inhibition of osteogenic differentiation, whereas miR-18a overexpression and the inhibition of both HIF1-α and NLRP3 reduced the effects of TNF-α. These findings are consistent with those of the animal experiments. CONCLUSION: miRNA-18a negatively affects HIF1-α/NLRP3 expression, inhibits inflammation-induced PANoptosis, and impairs osteogenic differentiation. Thus, it is a potential therapeutic candidate for developing anti-inflammatory strategies for infected bone diseases.

Novel biotin-linked amphiphilic calix[4]arene-based supramolecular micelles as doxorubicin carriers for boosted anticancer activity.

Supramolecular carrier-mediated chemotherapy is a highly attractive strategy for targeted drug delivery. In this study, four novel biotin-linked calix[4]arenes BPCA1-BPCA4 have been rationally designed to construct nano-complex with doxorubicin. The in vitro and in vivo assessments reveal that BPCA4-DOX with excellent stability are capable of affording significantly superior anti-tumor activity and lower side effects.

Extracorporeal Membrane Oxygenation for Acute Toxic Inhalations: Case Reports and Literature Review.

Previous studies have shown that poisoning is a major threat to human health. Inhalation of acute toxic gas has been linked to serious health consequences. Among the antidotes for poisoning currently used, supportive care is the most common intervention in clinical practice. Severe acute respiratory distress syndrome (ARDS) and/or refractory cardiogenic shock or cardiac arrest caused by toxins are associated with high mortality and are difficult to treat. Extracorporeal membrane oxygenation (ECMO) is an aggressive supportive measure used to manage severely poisoned patients. This study presents two cases of acute toxic gases inhalation, severe ARDS and circulatory instability induced by bromine inhalation, and ARDS induced by nitric acid inhalation which were successfully treated with ECMO. The ECMO techniques used in the animal models and in human cases to treat severe poisoning are described as well as the indications, contraindications, complications, and weaning of ECMO.

High-dose vitamin C suppresses the invasion and metastasis of breast cancer cells via inhibiting epithelial-mesenchymal transition.

PURPOSE: Vitamin C (VC) is a kind of essential nutrient in the body regarded as a canonical antioxidant during the past hundred years. However, the anti-cancer effect of VC is controversial. Our study is trying to clarify the relationship between VC dosage and breast cancer metastasis. METHODS: Human breast cancer cell lines Bcap37 and MDA-MB-453 were treated with VC at three different concentrations (low-dose, 0.01 mM; medium-dose, 0.1 mM; high-dose, 2 mM). Wound healing assays were conducted for migration assay; transwell tests were performed to detect the ability of cell invasion. The protein levels were evaluated by Western blot analysis or immunohistochemistry. Tumor xenografts in nude mice were built to test the effects of VC on breast cancer cell proliferation and metastasis. RESULTS: 0.01 and 0.1 mM VC promoted cell migration and invasion when compared with the control group, but 2 mM VC significantly suppressed cell migration and invasion of breast cancer cell lines. High-dose VC increased E-cadherin and reduced Vimentin, indicating that high-dose VC suppressed epithelial-mesenchymal transition (EMT) in breast cancer cells. Besides, high-dose VC inhibited cell invasion promoted by TGF-ß1 in breast cancer cells. Meanwhile, high-dose VC reversed the suppression of E-cadherin and enhancement of Vimentin induced by TGF-ß1 in breast cancer cells. Furthermore, high-dose VC significantly inhibited breast cancer metastasis in vivo. CONCLUSION: High-dose VC inhibits cell migration and invasion of breast cancer cell lines through suppressing EMT. Thus, it may be considered as an anticancer drug candidate for breast cancer patients.

In-orbit operation of an atomic clock based on laser-cooled 87Rb atoms.

Atomic clocks based on laser-cooled atoms are widely used as primary frequency standards. Deploying such cold atom clocks (CACs) in space is foreseen to have many applications. Here we present tests of a CAC operating in space. In orbital microgravity, the atoms are cooled, trapped, launched, and finally detected after being interrogated by a microwave field using the Ramsey method. Perturbing influences from the orbital environment on the atoms such as varying magnetic fields and the passage of the spacecraft through Earth's radiation belt are also controlled and mitigated. With appropriate parameters settings, closed-loop locking of the CAC is realized in orbit and an estimated short-term frequency stability close to 3.0 × 10-13τ-1/2 has been attained. The demonstration of the long-term operation of cold atom clock in orbit opens possibility on the applications of space-based cold atom sensors.

[Land ecological safety in Poyang Lake Eco-economic Zone: an evaluation based on matter-element model].

Base on the 2001-2007 related statistical data, and by means of matter-element model, an evaluation was conducted on the land ecological safety in Poyang Lake Eco-economic Zone. The land safety in the Eco-economic Zone was relatively fine in 2001, decreased to critical level in 2002-2004, and degraded to unsafe in 2005. From 2006, the safety level returned to critical, indicating a better safety status. This study showed that matter-element model had the advantages of simple calculation, clear indication, and higher accuracy, being able to provide another approach for regional land ecological safety evaluation.

[Assessment of land use environmental impacts in urban built-up area: a case study in main built-up area of Nanchang City].

Based on the relevant studies of land use environmental impacts and the characteristics of urban land use, a conceptual model on the assessment of land use environmental impacts in urban built-up area was established. This model grouped the land use environmental impacts in built-up area into four basic processes, i. e., detailization, abstractization, matching, and evaluation. A case study was conducted in the main built-up area of Nanchang City, with noise, smell, dust, and hazard as the impact factors. In the test area, noise had a widespread impact, its impacting area accounting for 59% of the total, smell and dust impacts centralized in the east and south parts, while hazard impact was centralized in the southeast part, an industrial area. This assessment model of four basic processes was practical, and could provide basis for the decision-making of urban land use management and planning.