LRRK2 G2019S and Parkinson's disease: insight from Neuroinflammation.

The multiple hypothesis holds that the pathogenesis of Parkinson's disease (PD) requires many factors such as heredity, environment and ageing. Mutations in Leucine-rich repeat kinase 2 (LRRK2) are recognized the risk factors of PD, and closely related to sporadic and familial PD and can regulate a variety of cellular pathways and processes. An Increasing number of studies has shown that glial hyperactivation-mediated neuroinflammation participates in dopaminergic neuron degeneration and pathogenesis of PD. LRRK2 is essential to the regulaton of chronic inflammation, especially for the central nervous system. The review spotlights on the novel development of LRRK2 on microglia and astrocytes, and explore their potential therapeutic targets, in order to provide a new insights in PD. Key messages: What is already known on this topic The G2019S mutation of LRRK2 is now recognised as a pathogenic mutation in PD. Previous studies have focused on the relationship between neurons and LRRK2 G2019S. What this study adds Neuroinflammation mediated by LRRK2 G2019S of glial cells affects the progress and development of PD and attention must be paid to the role of LRRK2 G2019S in glial cells in PD. How this study might affect research, practice or policy Developing anti-inflammatory drugs from the perspective of LRRK2 G2019S of glial cells is a new direction for the treatment of PD.

Investigation of the Clinical Studies of Traditional Chinese Medicine and Western Medicine in the Treatment of Disorders Related to Ventilators.

Objective: To observe the comprehensive treatment effect of Traditional Chinese Medicine on ventilator-related diseases. Methods: From January 2021 to August 2022, a total of 80 patients with ventilator-associated pneumonia were selected and divided into a test group and a matched control group based on the random number table, with 40 cases in each group. The control group received traditional Western medical care, and all patients were given tigecycline intravenously. The patients in the test group were treated with integrated traditional Chinese and Western medicine, and all patients were given tigecycline for injection by intravenous drip combined with Qingfei Huatan decoction orally. The two groups' therapeutic outcomes were contrasted, namely: procalcitonin (PCT), tumor necrosis factor (TNF)-α, hypersensitive C-reactive protein (CRP), blood oxygen saturation (PaO2), and white blood cell (WBC) count. Acute physiology and persistent health scores, clinical lung infection score, mechanical ventilation time, body temperature recovery time, and hospitalization time were recorded. Results: The effective Of cure in the test group was 37/40 (92.50%) and in the control group it was 30/40 (75.00%). The test group outperformed the control group by a considerable margin (P < .05). The levels of PCT, TNF-α, and hs-CRP were lower in the two groups, and the levels of TNF-α, PCT, and hs-CRP reduced with treatment (P < .05). The white blood cell and PaO2 levels were lower in the experimental group. APACHE II and CPIS scores decreased (P < .05). two groups,Postoperative body temperature recovery time, mechanical ventilation time, and hospital stay were all shortened (P < .05). Conclusion: The combination of traditional Chinese medicine and Western medicine has a positive clinical impact on ventilator-related diseases.

microRNA-15b-5p shuttled by mesenchymal stem cell-derived extracellular vesicles protects podocytes from diabetic nephropathy via downregulation of VEGF/PDK4 axis.

Diabetic nephropathy (DN) is a severe complication of diabetes lethal for end-stage renal disease, with less treatment methodologies and uncertain pathogenesis. In the current study, we determined the role of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) containing microRNA (miR)-15b-5p in DN. After extraction and identification of MSC-derived EVs, mouse podocyte line MPC5 was selected to establish an in vitro high-glucose (HG) cell model, where expression of miR-15b-5p, pyruvate dehydrogenase kinase 4 (PDK4) and VEGFA expression in tissues and cells were determined. The loss- and gain- function assays were conducted to determine the roles of miR-15b-5p, PDK4 and VEGFA. MPC5 cells were then co-cultured with MSC-derived EVs and their biological behaviors were detected by Western blot, CCK-8 assay, and flow cytometry. The binding relationship between miR-15b-5p and PDK43 by dual luciferase reporter gene assay. The expression of miR-15b-5p was downregulated in podocytes under HG environment, but highly expressed in mouse MSCs-derived EVs. EVs-derived miR-15b-5p could protect MPC5 cell apoptosis and inflammation. miR-15b-5p inhibited the expression of PDK4 by directly bound to the 3'UTR region of PDK4 gene. miR-15b-5p inhibits VEGF expression by binding to PDK4. Inhibition of PDK4 decreased VEGFA expression and reduced apoptosis and inflammation. Collectively, miR-15b-5p shuttled by MSC-derived EV can play protective roles in HG-induced mouse podocyte injury, possibly by targeting PDK4 and decreasing the VEGFA expression.

Neuroendoscopic surgery combined with Ommaya reservoir placement for cystic craniopharyngiomas: 11 years of experience in a single institution.

INTRODUCTION: Total resection of cystic craniopharyngiomas is challenging, especially for some large cystic tumors, because it is often associated with high recurrence and morbidity rates. Minimally invasive cyst decompression and continuous drainage are appropriate to manage clinical symptoms. We reviewed our experience of the past 11 years to determine the long-term effects of neuroendoscopic surgery (NES) combined with Ommaya reservoir (OR) for the treatment of cystic craniopharyngiomas. METHODS: We retrospectively analyzed the data of 15 adult patients with cystic craniopharyngiomas at a single institution with the primary goal to evaluate the treatment mode with initial adequate decompression of the cyst under visualization and continuous drainage. The study endpoints were functional outcome, cyst volume changes, and tumor progression. RESULTS: The median follow up was 77 (20-136) months. Clinical symptoms, e.g. increased intracranial pressure and visual impairment, could be rapidly improved after NES. The postoperative reduction in cyst volume (p < 0.001) and improvement in Karnofsky performance status (p < 0.001) were significant, and long-term tumor control was achieved in 10 patients (67%). Aspiration from the OR after progression of the tumor's cystic portion remains a major option, with only few patients requiring repeat NES procedures. No patient developed acute or severe clinical symptoms during follow up. CONCLUSIONS: NES could decompress the craniopharyngioma cyst under visualization and enable faster clinical-symptom improvement. The minimally invasive NES combined with OR allowed long-term symptom control in most patients without surgery-related injury. This palliative treatment strategy could be an alternative modality for cystic craniopharyngioma treatment.

Comprehensive analysis of chloroplast genome of Albizia julibrissin Durazz. (Leguminosae sp.).

MAIN CONCLUSION: The Albizia julibrissin chloroplasts have a classical chloroplast genome structure, containing 93 coding genes and 34 non-coding genes. Our research provides basic data for plant phylogenetic evolutionary studies. There is limited genomic information available for the important Chinese herb Albizia julibrissin Durazz. In this study, we constructed the chloroplast (Cp) genome of A. julibrissin. The length of the assembled Cp genome was 175,922 bp consisting of four conserved regions: a 5145 bp small single-copy (SSC) region, a 91,323 bp large single-copy (LSC) region, and two identical length-inverted repeat (IR) regions (39,725 bp). This Cp genome included 34 non-coding RNAs and 93 unique genes, the former contains 30 transfer and 4 ribosomal RNA genes. Gene annotation indicated some of the coding genes (82) in the A. julibrissin Cp genome classified in the Leguminosae family, with some to other related families (11). The results show that low GC content (36.9%) and codon bias towards A- or T-terminal codons may affect the frequency of gene codon usage. The sequence analysis identified 30 forward, 18 palindrome, and 1 reverse repeat > 30 bp length, and 149 simple sequence repeats (SSR). Fifty-five RNA editing sites in the Cp of A. julibrissin were predicted, most of which are C-to-U conversions. Analysis of the reverse repeat expansion or contraction and divergence area between several species, including A. julibrissin, was performed. The phylogenetic tree revealed that A. julibrissin was most closely related to Albizia odoratissima and Albizia bracteata, followed by Samanea saman, forming an evolutionary branch with Mimosa pudica and Leucaena trichandra. The research results are helpful for breeding and genetic improvement of A. julibrissin, and also provide valuable information for understanding the evolution of this plant.

Overexpression of E3 ubiquitin ligase Cbl attenuates endothelial dysfunction in diabetes mellitus by inhibiting the JAK2/STAT4 signaling and Runx3-mediated H3K4me3.

BACKGROUND: Diabetes mellitus (DM), a most common chronic disease, is featured with impaired endothelial function and bioavailability of nitric oxide (NO), while E3 ubiquitin ligase appears to alleviate endothelial dysfunction as a promising option for DM treatment. Herein, we aimed to determine whether E3 ubiquitin ligase casitas B-lineage lymphoma (Cbl) alleviates endothelial dysfunction in DM rats by JAK2/STAT4 pathway. METHODS: A rat model of DM was developed through intraperitoneal injection of streptozotocin, followed by collection of aortic tissues to determine the expression of Cbl, JAK2, runt-related transcription factor 3 (Runx3) and STAT4. Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose (HG) condition to induce DM as an in vitro model. With gain- and loss-function method, we assessed the aberrantly expressed Cb1 on endothelial dysfunction, NO production and apoptosis of HUVECs. RESULTS: Cbl was reduced in DM rat tissues and HG-induced HUVECs, where JAK2, Runx3 and STAT4 were elevated. It was found that overexpression of Cbl alleviated endothelial dysfunction by increasing NO production and restoring vasodilation and suppressing apoptosis of HUVECs. Mechanistically, Cb1 enhanced JAK2 ubiquitination and decreased JAK2 and STAT4 expression, where STAT4 improved Runx3 expression by regulating histone H3 lysine 4 trimethylation level. Overexpression of JAK2 and STAT4, or Runx3 increased apoptosis of HUVECs, abrogating the effect of Cb1 on endothelial function. CONCLUSION: In conclusion, Cbl alleviates endothelial dysfunction by inactivation of the JAK2/STAT4 pathway and inhibition of Runx3 expression in DM. These evidence might underlie novel Cbl-based treatment against DM in the future.

The cognitive impairment and risk factors of the older people living in high fluorosis areas: DKK1 need attention.

OBJECTIVE: To evaluate cognitive impairment and risk factors of elders in high fluoride drinking water areas and investigate whether DKK1 is involved in this disorder. METHODS: MoCA-B and AD-8 were used to measure the cognitive functions of 272 and 172 subjects over the age of 60 came from the high and normal fluoride drinking water areas respectively, general information and peripheral blood were collected, the level of SOD, GSH and MDA were measured, mRNA level of DKK1, the concentration of blood fluoride and the polymorphism of APOE were tested. RESULTS: The blood fluoride concentration, mRNA level of DKK1 and ratio of abnormal cognitive function of subjects in high fluorine drinking water areas were higher than those in normal areas. The level of SOD of subjects in high fluorine drinking water was low compared with those in normal areas. The level of MDA and GSH had no difference between the two crowds in different fluorine drinking water areas. There were differences in cigarette smoking, education, dental status, hypertension, hyperlipidaemia and APOE results between the two crowds in different fluorine drinking water areas. The mRNA level of DKK1 and the level of cognitive function showed a positive correlation and DKK1 was one of five risk factors involved in cognitive impairment of older people living in high fluorosis areas. CONCLUSIONS: The cognitive functions could be impaired in the older people living in high fluoride drinking water areas, and DKK1 may as a potential intervention point of this brain damage process need attention.

Neuroendoscopic treatment of giant cystic craniopharyngioma in the foramen magnum: report of two cases.

Pediatric craniopharyngioma is typically characterized by cystic changes and calcifications. It can grow from the suprasellar area to the posterior fossa (4%). This work reports that it is very rare for craniopharyngioma to grow from the suprasellar area to or beyond the level of the foramen magnum. Twelve patients with this disease have undergone one or several microsurgeries, and the microsurgical approaches are different. Among them, two cases died, and most of the remaining patients had certain complications such as endocrine dysfunction, nerve palsy, and subdural effusion. We treated two patients whose tumors had grown to the level of the foramen magnum, one of which reached C2 levels. Both cases were treated with a neuroendoscopy. There were no deaths and no complications. Our cases are the longest follow-up of this type of craniopharyngioma.

A mobile terminal application program was used for endotracheal tube cuff pressure measurement.

We studied the application of a mobile terminal application program in endotracheal tube (ETT) cuff pressure measurement to improve the implementation rate of scientific ETT cuff pressure measurement and to ensure that the pressure falls within the recommended range. A pre-post controlled study lasting for 18 months was undertaken in a 40-bed general intensive care unit (GICU). This included a 6-month baseline period (baseline group) and a 6-month intervention period (intervention group). The mobile terminal application program was applied to monitor the cuff pressure of endotracheal intubation as an intervention measure during the intervention period. ETT pressure was the main outcome measure, while gender, age, causes for ICU admission, sedation score, duration of prior intubation, size of ETT, and number of VAP patients were secondary outcomes. ETT cuff pressure was monitored 742 times in both the baseline group and the intervention group. A total of 56.9% of the cuff pressure measurements in the baseline group were within the recommended range, while 78.4% of measurements in the intervention group were within the recommended range, reflecting a statistically significant difference (P < 0.05). The application of the mobile terminal application program used for ETT cuff pressure measurement could improve the percentage of ETT cuff pressure measurements falling within the recommended range.

[Clinical application evaluation and revision suggestions of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute pharyngitis].

The purpose of this study is to analyze the obstructive factors of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute pharyngitis, and summarize the revision suggestions for follow-up revision and promotion. Clinical physicians from 181 hospitals in 27 regions of China were selected to complete the online questionnaire survey for statistical analysis of obstructive factors. We collected 501 copies of the applicability evaluation questionnaire and 503 copies of the application evaluation questionnaire. The obstructive factors mainly focused on limitation of the Guideline, inconvenience of access, particularity of primary medical structure and uneven distribution of surveyed subjects. As for amendments, it was suggested to improve the syndrome differentiation, indications, prescriptions, and add characteristic TCM therapies in Chinese medicine; it was suggested to clarify the time to use antibiotics in Western medicine. According to the results of this study, the relevant contents of the Guideline should be further improved so as to be better applied in clinical practice.

[Advantages and problems of traditional Chinese medicine in treatment of acute pharyngitis].

This paper systematically studies relevant literatures at home and abroad in recent years. China National Knowledge Internet (CNKI) was used to collect the literatures for acute pharyngitis treated with traditional Chinese medicine from January 1, 2006, to December 31, 2016, and the bibliometric method was employed for statistical analysis. A total of 493 papers were preliminarily selected. According to the inclusion criteria and exclusion criteria, 182 eligible articles were selected. According to the evaluation and analysis of the literatures, the Guidelines for Clinical Research of New Drugs is currently used as the common standards for the diagnosis and treatment of acute pharyngitis; Chinese patent medicines are the main traditional Chinese medicine for treating this disease; Decoctions for treatment of this disease include Lonicerae Japonicae Flos, Scutellariae Radix, Platycodonis Radix, Forsythiae Fructus, Glycyrrhizae Radix et Rhizoma, Scrophdlariae Radix, Isatidis Radix, and Ophiopogonis Radix; The bloodletting puncture is the common external therapy. Traditional Chinese medicine and Western medicine have their own characteristics in the treatment of this disease. Western medicine for the treatment of acute pharyngitis are mainly antiviral, antibiotic and glucocorticoid drugs, whose disadvantages are toxicity, side effects, drug resistance and double infections. Traditional Chinese medicine doctors have rich experiences in the treatment of the disease, which is characterized by treatment determination based on syndrome differentiation, safe and reliable medication, significant curative effect, low drug resistance, and wide varieties of traditional Chinese medicine forms, convenient portability and taking, low price, and low toxic and side effects. It is an arduous and significant task to explore traditional Chinese medicine, and study and develop new-type effective drugs.

3 M antimicrobial incise drape combined with MEBO in wound recovery of postoperative hypospadias surgery.

OBJECTIVE: To evaluate the efficacy of different dressing methods in wound healing and the postoperative outcome in children who underwent hypospadias repair. METHODS: Altogether 109 children with distal hypospadias who underwent urethroplasty were recruited from our hospital between January 2021 and March 2023. All patients were randomized in two groups according to the different dressing methods: Group A receiving 3 M antimicrobial incise drape + MEBO (moisture-exposed burn ointment) and Group B receiving absorbent dressing + elastic bandage dressing. The age at surgery, operation time, bleeding during the dressing, postoperative changes in glans color, dressing fell off, comfort of children during the dressing, difficulty in dressing removal, and degree of pain during dressing removal were compared between the two groups. RESULTS: Differences in age at surgery (p = 0.337) and operation time (p = 0.055) were not significant between the two groups. The overall effectiveness of the dressing was better in Group A than that in Group B. Only five cases in Group A had blood leakage after dressing (p = 0.006), and there was no dressing dislocation (p < 0.001) or glans color abnormality (p < 0.001). Moreover, the number of complication cases was less. The overall comfort and pain degree during dressing removal in Group A was better than that in Group B (p < 0.001). CONCLUSION: Postoperative dressing using 3 M antimicrobial incise drape + MEBO can achieve lower incidence rates of bleeding during dressing, postoperative glans darkening, and dressing falling off, a lower pain degree during dressing removal, and a better overall comfort level than those of the control group. This method is cost-effective and clinically safe, which contributes to the postoperative recovery of children with hypospadias and is thus worth promoting and applying.

Safety, pharmacokinetics, and pharmacodynamics of anti-IL-4Rα antibody SHR-1819 in healthy subjects: A randomized, controlled phase I study.

SHR-1819 is a novel anti-IL-4Rα monoclonal antibody currently under clinical development for use in patients with type 2 inflammatory diseases. In this randomized, double-blind, placebo-controlled, single-dose escalation phase I trial, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR-1819 in healthy subjects. Subjects received a single subcutaneous injection of SHR-1819 or placebo, with dose escalation starting at 60 mg and subsequently increasing to 120, 240, 360, and 720 mg. A total of 42 eligible subjects were randomized, and 33 received SHR-1819 (1 subject in the 60 mg cohort and 8 subjects each in the 120, 240, 360 , and 720 mg cohorts) and 9 received placebo. SHR-1819 was well-tolerated, with the majority of adverse events being mild in severity. The exposure of SHR-1819 increased in a manner greater than proportionally with a dose range of 120 to 720 mg. The median Tmax was within 4-7 days (60-720 mg), and the mean half-life ranged from 2.88 to 5.97 days (120-720 mg). The clearance rate of SHR-1819 exhibited a decrease with increasing dose level. Administration of SHR-1819 resulted in a certain degree of reduction in the percentage change from baseline in concentrations of inflammatory biomarkers TARC/CCL17 and IgE, while the reduction of TARC/CCL17 concentrations showed a dose-dependent trend. More than half of the total subjects treated with SHR-1819 were reported antidrug antibody-negative. The preliminary data from this phase I study support further development of SHR-1819 for the treatment of type 2 inflammatory diseases.

Altered functional brain activity in first-episode major depressive disorder treated with electro-acupuncture: A resting-state functional magnetic resonance imaging study.

Background: Previous studies have found electroacupuncture could improve the clinical symptoms of first-episode major depressive disorder (MDD), but the exact neural mechanism of action needs to be further elucidated. Methods: Twenty-eight first-episode MDD patients were randomly divided into 14 electro-acupuncture stimulation (EAS) groups and 14 sham-acupuncture stimulation (SAS) groups, and clinical symptoms were assessed and functional magnetic resonance imaging (fMRI) scans were done in both groups. Amplitude of low-frequency fluctuations (ALFF) was used to observe the changes between the pre-treatment and post-treatment in the two groups, and the altered brain areas were selected as region of interest (ROI) to observe the FC changes. Meanwhile, the correlation between the altered clinical symptoms and the altered ALFF and FC of brain regions in the two groups was analyzed. Results: The EAS significantly decreased the HAMD-24 and HAMA-14 scores of MDD than SAS group. The imaging results revealed that both groups were able to increase the ALFF of the left middle temporal gyrus and the left cerebellar posterior lobe. When using the left middle temporal gyrus and the left posterior cerebellar lobe as ROIs, EAS group increased the FC between the left middle temporal gyrus with the left superior frontal gyrus, the left middle frontal gyrus, and the left hippocampus, and decreased the FC between the left posterior cerebellar lobe and the left calcarine gyrus, while SAS group only increased the FC between the left middle temporal gyrus with the left superior frontal gyrus. The alternations in clinical symptoms after EAS treatment were positively correlated with the altered ALFF values in the left middle temporal gyrus and the altered FC values in the left middle temporal gyrus and the left middle frontal gyrus. Conclusion: EA demonstrates modulation of functional activity in the default mode network (DMN), sensorimotor network (SMN), cognitive control network (CCN), limbic system, and visual network (VN) for the treatment of the first-episode MDD. Our findings contribute to the neuroimaging evidence for the efficacy of EAS.

[Study on MSO/GO-based determination method for trace amount of aqueous Hg2+].

OBJECTIVE: To establish a highly sensitive fluorometric nanobiosensor for determination of aqueous mercury ions (Hg(2+)) using optimized mercury-specific oligonucleotide (MSO) probes and graphene oxide (GO). METHODS: The nanobiosensor was assembled by attaching the self-designed MSO(1) (5' end labeled with fluorophore carboxyfluorescein (FAM), denoted as FAM-MSO(1)) and MSO(2) to the surface of GO through strong non-covalent bonding forces. Upon the addition of Hg(2+), the formation of the T-Hg(2+)-T configuration desorbed the FAM-MSO(1) and MSO(2) from the surface of GO, resulting in a restoration of the fluorescence of FAM-MSO(1). Using the specific mispairing of T-Hg(2+)-T and the changes in fluorescent signals in solutions, quantitative analysis of Hg(2+) could be performed. RESULTS: The average thickness of the prepared GO sheets was only 1.4 nm. For the Hg(2+) nanobiosensor, the optimum concentrations of FAM-MSO(1) and MSO(2) were both 1 µmol/L, the optimum volume of 0.5 g/L GO was 5 µL, and the limit of detection was 10 pmol/L; it had low cross-reactivity with 10 other kinds of non-specific metal ions; the fluorescence recovery efficiency was up to 65% in the re-determination of Hg(2+) after addition of Na(2)S(2)O(3). CONCLUSION: The MSO/GO-based nanobiosensor is convenient to operate, highly sensitive, highly specific, highly accurate, and reusable. It can be applied to determine trace amount of Hg(2+) in aqueous solutions.

Modulation of skyrmionic magnetic textures in two-dimensional vdW materials and their heterostructures.

The intrinsic magnetism observed in two-dimensional (2D) van der Waals (vdW) materials provides a unique opportunity for exploring the 2D topological magnetic textures, in particular skyrmionic magnetic textures (SMTs) including skyrmion and its topological equivalents. Since the experimental discovery of skyrmions in the 2D vdW materials and their heterostructures, a critical challenge lies in the control of these SMTs to translate their intriguing features into spintronic applications. Here, we review the recent experimental and theoretical progress on the modulations of SMTs in 2D vdW monolayer materials and their heterostructures. Besides well-established basic modulation factors including temperature, magnetic field and sample thickness, we present the experimental realization of mobility and transition driven by electric current, and the theoretical prediction of diverse magnetoelectric modulations by electric field. Considering the 2D character of vdW layered materials, strain and stacking style are also efficient approaches to tune the magnetic textures.

Role of sodium pyruvate in maintaining the survival and cytotoxicity of Staphylococcus aureus under high glucose conditions.

Glucose is a crucial carbon source for the growth of Staphylococcus aureus, but an excess of glucose is detrimental and even leads to cell death. Pyruvate, the central metabolite of glycolysis, has been shown to have anti-inflammatory and antioxidant properties. This study aimed to investigate the protective effect of pyruvate on S. aureus under high glucose conditions. Sodium pyruvate greatly increased the cytotoxicity of S. aureus strain BAA-1717 to human erythrocytes and neutrophils in vitro. However, the cytotoxicity and survival of S. aureus were significantly reduced by high glucose, which was restored to normal levels by the addition of sodium pyruvate. The expression of hlg and lukS in S. aureus was higher in the LB-GP cultures than that in LB-G cultures, but there was no significant difference in cytotoxicity between LB-GP and LB-G cultures. Furthermore, the hemolytic activity of S. aureus supernatants could be inhibited by the cell-free culture medium (CFCM) of LB-G cultures, suggesting that high levels of extracellular proteases were presence in the CFCM of LB-G cultures, resulting in degradation of the hemolytic factors. The expression of sarA, which negatively regulates extracellular protease secretion, was higher in LB-GP cultures than that in LB-G cultures. Additionally, sodium pyruvate increased acetate production in S. aureus, which helps maintain cell viability under acidic environment. In conclusion, pyruvate plays an important role in the survival and cytotoxicity of S. aureus under high glucose conditions. This finding may aid in the development of effective treatments for diabetic foot infections.

Prevalence and adverse outcomes of pre-operative frailty in patients undergoing carotid artery revascularization: a meta-analysis.

Introduction: Frailty can lead to a decrease in the patient's resistance to interference such as injury and disease, and cause a series of complications. An increasing number of studies have found that pre-operative frailty exacerbates the occurrence of adverse events after carotid artery revascularization, but an integrated quantitative analysis is currently lacking. Therefore, we conducted a meta-analysis to evaluate the impact of pre-operative frailty on patients undergoing carotid artery revascularization. Method: According to the PRISMA guidelines, we systematically searched for relevant studies on Medline, Embase, Ovid, CINAHL, Web Of Science, and Cochrane Library from establishment until June 2023. Summarize the risk of adverse outcome events through OR and 95% CI. Results: A total of 16 cohort studies were included, including 1692338 patients. Among patients who underwent carotid artery revascularization surgery, the prevalence of pre-operative frailty was 36% (95% CI = 0.18-0.53, P < 0.001). Compared with non frail individuals, frail individuals have an increased risk of mortality (OR = 2.35, 95% CI = 1.40-3.92, P = 0.001, I2 = 94%), stroke (OR = 1.33, 95% CI = 1.10-1.61, P = 0.003, I2 = 71%), myocardial infarction (OR = 1.86, 95% CI = 1.51-2.30, P < 0.001, I2 = 61%), and non-home discharge (OR = 2.39, 95% CI = 1.85-3.09, P < 0.001, I2 = 63%). Conclusion: The results of this article show that patients undergoing carotid artery revascularization have a higher prevalence of pre-operative frailty, which can lead to an increased risk of postoperative death, stroke, myocardial infarction, and non-home discharge. Strengthening the assessment and management of frailty is of great significance for patient prognosis. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=416234, identifier: CRD42023416234.

PIAS1 impedes vascular endothelial injury and atherosclerotic plaque formation in diabetes by blocking the RUNX3/TSP-1 axis.

The protein PIAS1 functions as a type of ubiquitin-protease, which is known to play an important regulatory role in various diseases, including cardiovascular diseases and cancers. Its mechanism of action primarily revolves around regulating the transcription, translation, and modification of target proteins. This study investigates role and mechanism of PIAS1 in the RUNX3/TSP-1 axis and confirms its therapeutic effects on diabetes-related complications in animal models. A diabetic vascular injury was induced in human umbilical vein endothelial cells (HUVECs) by stimulation with H2O2 and advanced glycation end product (AGE), and a streptozotocin (STZ)-induced mouse model of diabetes was constructed, followed by detection of endogenous PIAS1 expression and SUMOylation level of RUNX3. Effects of PIAS1 concerning RUNX3 and TSP-1 on the HUVEC apoptosis and inflammation were evaluated using the ectopic expression experiments. Down-regulated PIAS1 expression and SUMOylation level of RUNX3 were identified in the H2O2- and AGE-induced HUVEC model of diabetic vascular injury and STZ-induced mouse models of diabetes. PIAS1 promoted the SUMOylation of RUNX3 at the K148 site of RUNX3. PIAS1-mediated SUMOylation of RUNX3 reduced RUNX3 transactivation activity, weakened the binding of RUNX3 to the promoter region of TSP-1, and caused downregulation of TSP-1 expression. PIASI decreased the expression of TSP-1 by inhibiting H2O2- and AGE-induced RUNX3 de-SUMOylation, thereby arresting the inflammatory response and apoptosis of HUVECs. Besides, PIAS1 reduced vascular endothelial injury and atherosclerotic plaque formation in mouse models of diabetes by inhibiting the RUNX3/TSP-1 axis. Our study proved that PIAS1 suppressed vascular endothelial injury and atherosclerotic plaque formation in mouse models of diabetes via the RUNX3/TSP-1 axis.

Nucleic Acid Prevalence of Zoonotic Babesia in Humans, Animals and Questing Ticks, a Systematic Review and Meta-Analysis.

Background: Zoonotic Babesia infections are an emerging public health threat globally. The geographical distribution, animal reservoirs and tick vectors vary greatly across Babesia species, and estimations of prevalence reported in works within the literature are also quite different. Better prevalence estimates and identification of moderators are needed to understand the global transmission risk of different zoonotic Babesia species, and to provide crucial background information for the diagnosis, treatment and control of zoonotic babesiosis. Methods: We conducted a systematic review and meta-analysis to determine the global nucleic acid prevalence of different zoonotic Babesia species in humans, animals and ticks. Relevant publications were obtained from several electronic databases and grey literature up to December 2021. Articles were included if they were published in English or Chinese and reported the nucleic acid prevalence of zoonotic Babesia species in humans, animals or ticks. The pooled estimates of prevalence were determined using a random effect model. Heterogeneity was investigated using subgroup analyses and random effect meta-regression models. Results: Of 3205 unique studies, 28 were included by the systematic review of zoonotic Babesia for humans, 79 for animals and 104 for ticks. The results showed overall pooled estimates of nucleic acid prevalence for the following: B. microti-1.93% (0.32-4.69%) in humans; B. microti-7.80% (5.25-10.77%), B. divergens-2.12% (0.73-4.08%) and B. venatorum-1.42% (0.30-3.16%) in animals; and B. microti-2.30% (1.59-3.13%), B. divergens-0.16% (0.05-0.32%), and B. venatorum-0.39% (0.26-0.54%) in questing ticks. The type of population, animal reservoir or tick vector, detecting method and continent were moderators possibly associated with heterogeneity, yet the remaining heterogeneity that was not explained was still substantial (all QE p values < 0.05). Conclusions:B. microti is the most prevalent and widely distributed zoonotic Babesia species globally. The wide range of suitable animal reservoirs and potential transmission vectors and high prevalence in animals and ticks may contribute to the worldwide distribution of B. microti. Other zoonotic Babesia species were relatively less prevalent and were reported in quite limited areas.