Association Between Cognitive Function and Risk of Chronic Kidney Disease: A Longitudinal Cohort and Mendelian Randomization Study.

OBJECTIVE: To investigate the causal dose-response association between cognitive function and the risk of chronic kidney disease (CKD) by a longitudinal cohort and mendelian randomization study. METHODS: The longitudinal cohort study included 396,600 participants without prior dementia and CKD from the UK Biobank. Cognitive function (including prospective memory, numeric memory, visuospatial memory, reaction time, and reasoning ability) was assessed by computerized touchscreen tests. Global cognitive function was defined as a composite score of those specific cognitive domains. A 2-stage mendelian randomization analysis was conducted with 12,979 cases of CKD and 379,424 controls. Genetically predicted global cognitive function was instrumented with 91 confirmed genome-wide significant variants. The study outcome was new-onset CKD. The study was conducted from March 13, 2006, to September 30, 2021. RESULTS: During a median follow-up of 12.5 years, new-onset CKD developed in 13,090 participants. Per 1 SD score increments in reaction time (adjusted hazard ratio [HR], 0.97; 95% CI, 0.95 to 0.99), reasoning ability (adjusted HR, 0.91; 95% CI, 0.88 to 0.94), and global cognitive function (adjusted HR, 0.96; 95% CI, 0.95 to 0.98) were associated with a significantly lower risk of new-onset CKD. Compared with an incorrect answer in the prospective memory test, a correct answer was associated with a lower risk of new-onset CKD (adjusted HR, 0.82; 95% CI, 0.76 to 0.88). Mendelian randomization analyses found that per 1 SD score increments in genetically predicted global cognitive function resulted in a significantly (7%; 95% CI, 2% to 12%) lower risk of new-onset CKD. CONCLUSION: A better cognitive function is causally associated with a lower risk of CKD in participants without prior dementia.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study

Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

The clinical characteristics analysis of serum markers for the cardiovascular system in early-stage COVID-19 patients.

Background: This study aimed to investigate alterations in serum markers [creatine kinase-MB (CKMB), cardiac troponin T (cTnT), myoglobin (Myo), B-type natriuretic peptide (BNP), D-dimer (DD), procalcitonin (PCT) and interleukin-6 (IL6)] in early Omicron variant infection and analyzed their correlation with clinical parameters. Methods: Retrospective analysis of 1,138 mild/asymptomatic cases at Tianjin First Central Hospital, including age, gender, serum markers and nucleic acid test results. Statistical analysis used SPSS software, version 24.0. Results: Elevated cTnT, BNP (125-400), and DD (0.55-1.10) levels were prevalent at 12.92%, 15.64%, and 14.50%, respectively. Females had significantly higher proportions with slightly elevated BNP (19.34%) and DD (19.69%) levels. Patients over 35 had a higher proportion of slight elevation in BNP (20.00%). Abnormal levels of serum markers were significantly associated with older age, increased PCT and IL6 levels, as well as delayed nucleic acid clearance. Additionally, levels of immunoglobulin G (IgG) were notably reduced in these cases. Patients with prolonged nucleic acid clearance (>14 days) had higher BNP and DD levels upon admission. Logistic regression identified PCT (OR = 237.95) as the most significant risk factor for abnormal serum markers for cardiovascular system injury. Conclusion: Early Omicron infection might do subclinical damage to the cardiovascular system. Elevated cTnT, BNP and DD levels were correlated with age, gender, inflammatory factors, and IgG. Notably, high PCT level emerged as the most robust predictor of abnormal serum biomarkers.

[Clinical advantage staging and underlying mechanisms of Wangbi Tablets against knee osteoarthritis based on "disease-formula" interaction network].

The clinical advantage staging and underlying mechanisms of Wangbi Tablets against knee osteoarthritis(KOA) were studied based on the "disease-formula" interaction network. Firstly, the clinical symptoms and related genes corresponding to Wangbi Tablets and KOA in the acute, remission, and recovery phases were collected from clinical guidelines/consensus and SoFDA database, and the putative targets of Wangbi Tablets were obtained from ETCM 2.0. Then, Jaccard similarity and cosine similarity were employed to assess the similarities of clinical symptoms, genes, and enriched pathways between Wangbi Tablets and KOA in different phases. The "disease-formula" interaction network of the drug targets and disease genes was constructed, and the key targets were screened by topological feature calculation. KEGG and Reactome database were used for the functional enrichment of the key targets, on the basis of which the functional characteristics of Wangbi Tablets against KOA in the acute, remission, and recovery phases were predicted. Finally, the SW1353 cells exposed to lipopolysaccharide were used to decipher the mechanism of Wangbi Tablets against KOA. The results showed that 92/3 921, 138/3 708, 139/3 800, and 196/3 946 clinical symptoms and the related genes corresponded to KOA in the acute, remission, and recovery phases and Wangbi Tablets were collected from SoFDA, and 260 putative targets of Wangbi Tablets were obtained from ETCM 2.0. Wangbi Tablets had highest similarity of clinical symptoms, genes, and enriched pathways with KOA in the remission phase and the secondary highest similarity with KOA in the recovery phase. The key targets of Wangbi Tablets mainly participated in the regulation of immunity-inflammation imbalance and exerted pain-relieving and bone-protecting effects to alleviate symptoms such as knee joint pain, joint swelling, soreness, fatigue, and dysfunction. Intriguingly, the key targets of Wangbi Tablets possessed antioxidant effects during KOA in the acute and remission phases, while they maintained material and energy metabolism homeostasis and protected vessels during KOA in the recovery phase. The cell experiment indicated that Wangbi Tablets down-regulated the expression of interleukin(IL)-6, IL-1ß, tumor necrosis factor-α(TNF-α), and Bcl-2-associated X protein(Bax)/B-cell lymphoma 2(Bcl-2) via regulating the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) signaling pathway. The findings lay a theoretical foundation for further clarifying the clinical advantage stage and precise clinical application of Wangbi Tablets in treating KOA.

Evaluation of protective immunity induced by a DNA vaccine encoding SAG2 and SRS2 against Toxoplasma gondii infection in mice.

Toxoplasma gondii is an important protozoan pathogen, which can cause severe diseases in the newborns and immunocompromised individuals. Developing an effective vaccine against Toxoplasma infection is a critically important global health priority. Immunofluorescence staining analysis revealed that TgSAG2 and TgSRS2 are membrane associated and displayed on the surface of the parasite. Immunizations with pBud-SAG2, pBud-SRS2 and pBud-SAG2-SRS2 DNA vaccines significantly increased the production of specific IgG antibodies. Immunization with pBud-SAG2-SRS2 elicited cellular immune response with higher concentrations of IFN-γ and IL-4 compared to the control group. Antigen-specific lymphocyte proliferations in the pBud-SRS2 and pBud-SAG2-SRS2 groups were significantly higher compared to that in the control group. Furthermore, 30 % of mice immunized with pBud-SAG2-SRS2 survived after the challenge infection with virulent T. gondii RH tachyzoites. This study revealed that immunization with pBud-SAG2-SRS2 induced potent immune responses, and has the potential as a promising vaccine candidate for the control of T. gondii infection.

Bacterial exonuclease III expands its enzymatic activities on single-stranded DNA.

Bacterial exonuclease III (ExoIII), widely acknowledged for specifically targeting double-stranded DNA (dsDNA), has been documented as a DNA repair-associated nuclease with apurinic/apyrimidinic (AP)-endonuclease and 3'→5' exonuclease activities. Due to these enzymatic properties, ExoIII has been broadly applied in molecular biosensors. Here, we demonstrate that ExoIII (Escherichia coli) possesses highly active enzymatic activities on ssDNA. By using a range of ssDNA fluorescence-quenching reporters and fluorophore-labeled probes coupled with mass spectrometry analysis, we found ExoIII cleaved the ssDNA at 5'-bond of phosphodiester from 3' to 5' end by both exonuclease and endonuclease activities. Additional point mutation analysis identified the critical residues for the ssDNase action of ExoIII and suggested the activity shared the same active center with the dsDNA-targeted activities of ExoIII. Notably, ExoIII could also digest the dsDNA structures containing 3'-end ssDNA. Considering most ExoIII-assisted molecular biosensors require the involvement of single-stranded DNA (ssDNA) or nucleic acid aptamer containing ssDNA, the activity will lead to low efficiency or false positive outcome. Our study revealed the multi-enzymatic activity and the underlying molecular mechanism of ExoIII on ssDNA, illuminating novel insights for understanding its biological roles in DNA repair and the rational design of ExoIII-ssDNA involved diagnostics.

Influence of acupuncture and moxibustion on gastrointestinal function and adverse events in gastric cancer patients after surgery and chemotherapy: a meta-analysis.

OBJECTIVE: The impact of acupuncture and moxibustion on postoperative complications and adverse events (AEs) of chemotherapy in patients with gastric cancer (GC) has been investigated. Through a meta-analysis of existing randomized controlled trials (RCTs), this study sought to strengthen the evidentiary basis to help investigators further understand the effects of moxibustion and acupuncture on postoperative complications and AEs of chemotherapy among GC patients. METHODS: Embase, Web of Science, PubMed, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database for Chinese Technical Periodicals were searched to collect RCTs on effects of acupuncture and moxibustion on gastrointestinal function and AEs among GC patients undergoing surgery and chemotherapy. Outcome measures included postoperative gastrointestinal recovery (bowel sound recovery time, time to first flatus/defecation/feeding), the incidence of AEs (nausea and vomiting, abdominal distension, and diarrhea), myelosuppression (white blood cells, hemoglobin, and platelet), and immune function indicators (CD3+ and CD4+). To assess quality, the Cochrane Risk of Bias Tool was utilized. Review Manager 5.4 was implemented to do the meta-analysis. RESULTS: Fifteen eligible RCTs involved 1259 patients. Meta-analysis results showed that the experimental group had a significantly shorter bowel sound recovery time (MD = - 14.57, 95% CI = [- 18.97, - 10.18], P < 0.00001), time to first flatus (MD = - 17.56, 95% CI = [- 22.23, - 12.88], P < 0.00001), time to first defecation (MD = - 17.05, 95% CI = [- 21.02, - 13.09], P < 0.00001), and time to first feeding (MD = - 23.49, 95% CI = [- 28.81, - 18.17], P < 0.00001) than the control group. There were significant decreases in the incidence of nausea and vomiting (RR = 0.46, 95% CI = [0.21, 1.02], P = 0.05) and abdominal distension (RR = 0.45, 95% CI = [0.27, 0.75], P = 0.002) observed in the experimental group in comparison with the control group. The experimental group demonstrated a significant increase in white blood cell counts in comparison with to the control group (MD = 0.89, 95% CI = [0.23, 1.55], P = 0.008). The experimental group showed significantly higher levels of CD3+ (MD = 7.30, 95% CI = [1.86, 12.74], P = 0.009) and CD4+ (MD = 2.75, 95% CI = [1.61, 3.90], P < 0.00001) than the control group. CONCLUSION: Among GC patients, acupuncture and moxibustion can aid in gastrointestinal function recovery, reduce the incidence of AEs of surgery and chemotherapy, and improve immune function.

Large-Scale Proteomics Improve Prediction of Chronic Kidney Disease in People With Diabetes.

OBJECTIVE: To develop and validate a protein risk score for predicting chronic kidney disease (CKD) in patients with diabetes and compare its predictive performance with a validated clinical risk model (CKD Prediction Consortium [CKD-PC]) and CKD polygenic risk score. RESEARCH DESIGN AND METHODS: This cohort study included 2,094 patients with diabetes who had proteomics and genetic information and no history of CKD at baseline from the UK Biobank Pharma Proteomics Project. Based on nearly 3,000 plasma proteins, a CKD protein risk score including 11 proteins was constructed in the training set (including 1,047 participants; 117 CKD events). RESULTS: The median follow-up duration was 12.1 years. In the test set (including 1,047 participants; 112 CKD events), the CKD protein risk score was positively associated with incident CKD (per SD increment; hazard ratio 1.78; 95% CI 1.44, 2.20). Compared with the basic model (age + sex + race, C-index, 0.627; 95% CI 0.578, 0.675), the CKD protein risk score (C-index increase 0.122; 95% CI 0.071, 0.177), and the CKD-PC risk factors (C-index increase 0.175; 95% CI 0.126, 0.217) significantly improved the prediction performance of incident CKD, but the CKD polygenic risk score (C-index increase 0.007; 95% CI -0.016, 0.025) had no significant improvement. Adding the CKD protein risk score into the CKD-PC risk factors had the largest C-index of 0.825 (C-index from 0.802 to 0.825; difference 0.023; 95% CI 0.006, 0.044), and significantly improved the continuous 10-year net reclassification (0.199; 95% CI 0.059, 0.299) and 10-year integrated discrimination index (0.041; 95% CI 0.007, 0.083). CONCLUSIONS: Adding the CKD protein risk score to a validated clinical risk model significantly improved the discrimination and reclassification of CKD risk in patients with diabetes.

An inhibitory mechanism of AasS, an exogenous fatty acid scavenger: Implications for re-sensitization of FAS II antimicrobials.

Antimicrobial resistance is an ongoing "one health" challenge of global concern. The acyl-ACP synthetase (termed AasS) of the zoonotic pathogen Vibrio harveyi recycles exogenous fatty acid (eFA), bypassing the requirement of type II fatty acid synthesis (FAS II), a druggable pathway. A growing body of bacterial AasS-type isoenzymes compromises the clinical efficacy of FAS II-directed antimicrobials, like cerulenin. Very recently, an acyl adenylate mimic, C10-AMS, was proposed as a lead compound against AasS activity. However, the underlying mechanism remains poorly understood. Here we present two high-resolution cryo-EM structures of AasS liganded with C10-AMS inhibitor (2.33 Å) and C10-AMP intermediate (2.19 Å) in addition to its apo form (2.53 Å). Apart from our measurements for C10-AMS' Ki value of around 0.6 µM, structural and functional analyses explained how this inhibitor interacts with AasS enzyme. Unlike an open state of AasS, ready for C10-AMP formation, a closed conformation is trapped by the C10-AMS inhibitor. Tight binding of C10-AMS blocks fatty acyl substrate entry, and therefore inhibits AasS action. Additionally, this intermediate analog C10-AMS appears to be a mixed-type AasS inhibitor. In summary, our results provide the proof of principle that inhibiting salvage of eFA by AasS reverses the FAS II bypass. This facilitates the development of next-generation anti-bacterial therapeutics, esp. the dual therapy consisting of C10-AMS scaffold derivatives combined with certain FAS II inhibitors.

Comparison of Objective Visual Quality Following SMILE and SmartPulse Technology-Assisted TransPRK at a 1,050-Hz Ablation Frequency for Moderate-to-High Myopia.

PURPOSE: To compare the objective visual quality of moderate-to-high myopia corrected by small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (TransPRK) at a 1,050-Hz ablation frequency, assisted by Smart-Pulse technology (SCHWIND eye-tech-solutions). METHODS: This study involved 123 patients (123 eyes) with moderate-to-high myopia between July 2020 and January 2021. They were categorized into the SMILE group (67 patients, 67 eyes) and the TransPRK group (56 patients, 56 eyes). Follow-ups were conducted at 6 months postoperatively to record the logarithm of the minimum angle of resolution visual acuity, and the Strehl ratio and higher order aberrations were measured using the Sirius anterior segment analysis device (SCHWIND eye-tech-solutions) under a 6-mm pupil diameter at various postoperative intervals. RESULTS: At 1 week and 1 month postoperatively, the uncorrected distance visual acuity (UDVA) in the SMILE group was superior to that in the TransPRK group (P < .05 for both). At 1 week and 1 month postoperatively, the Strehl ratio value in the SMILE group was higher than that in the TransPRK group (P < .05 for both). At 1, 3, and 6 months postoperatively, coma was greater in the SMILE group than in the TransPRK group (P < .05 for all). Spherical aberrations were lower in the SMILE group than in the TransPRK group at 3 and 6 months postoperatively (P < .05). At 6 months postoperatively, UDVA was -0.09 ± 0.08 and -0.11 ± 0.05 logMAR in the SMILE and TransPRK groups, respectively, which exceeded their preoperative corrected distance visual acuity of -0.05 ± 0.04 and -0.09 ± 0.08 logMAR (all P < .001). Compared with preoperative values, the Strehl ratio, total higher order, coma, and spherical aberration differences were significantly increased postoperatively in both groups (all P < .001). CONCLUSIONS: Both surgical methods improved UDVA and each had its advantages. The visual quality of SMILE was superior at 1 week and 1 month postoperatively (Strehl ratio values were higher than those of the TransPRK group), and its spherical aberration was lower than that of the TransPRK group at 3 and 6 months; TransPRK with SmartPulse technology with a 1,050-Hz ablation frequency showed that coma was significantly lower than that of the SMILE group at 1, 3, and 6 months postoperatively. [J Refract Surg. 2024;40(7):e490-e498.].

cUMP elicits inter-endothelial gap formation during Pseudomonas aeruginosa infection.

P. aeruginosa utilizes a type 3 secretion system to intoxicate host cells with the nucleotidyl cyclase ExoY. After activation by its host cell cofactor, filamentous actin, ExoY produces purine and pyrimidine cyclic nucleotides, including cAMP, cGMP, and cUMP. ExoY-generated cyclic nucleotides promote inter-endothelial gap formation, impair motility, and arrest cell growth. The disruptive activities of cAMP and cGMP during P. aeruginosa infection are established; however, little is known about the function of cUMP. Here, we tested the hypothesis that cUMP contributes to endothelial cell barrier disruption during P. aeruginosa infection. Utilizing a membrane permeable cUMP analog, cUMP-AM, we revealed that during infection with catalytically inactive ExoY, cUMP promotes inter-endothelial gap formation in cultured PMVECs and contributes to increased filtration coefficient in the isolated perfused lung. These findings indicate that cUMP contributes to endothelial permeability during P. aeruginosa lung infection.

Differences in regional distribution and inequality in health workforce allocation in hospitals and primary health centers in China: A longitudinal study.

BACKGROUND: In 2009, China launched a new round of healthcare reform to provide households with secure, efficient, convenient, equitable and affordable healthcare services. Healthcare reform is underpinned by three critical pillars: the health workforce, funding, and infrastructure, with reform of the health workforce being particularly significant. OBJECTIVE: This study analyses the disparities in regional distribution and the inequity of healthcare workforce allocation across hospitals and primary health centers in China over twelve years. DESIGN: Retrospective longitudinal data from the National Health Statistics Yearbook 2011-2022 and National Statistical Yearbook in China from 2011 to 2022 were collected for analysis. PARTICIPANTS: The focus was on hospitals and primary health centers, explicitly examining their health technician and nursing workforce. METHODS: The research utilized four key indicators of the healthcare workforce to evaluate the distribution of health resources between hospitals and primary health centers. Furthermore, the Gini coefficient and Theil index were employed to assess the inequality in allocating the health workforce. RESULTS: Between 2010 and 2021, there was a nationwide increase in the ratio of health workers per 1000 population in hospitals and primary health centers. It is noted that rural districts had higher ratios than urban districts in terms of the number of health technicians and nurses per 1000 population, whether in hospitals or primary health centers; western districts had higher ratios than eastern and central districts did. In the same year, at different levels of medical institutions, the Theil indices of health technicians and nurses in hospitals were lower than those in primary health centers in terms of both demographic and geographical dimensions. Regarding the allocation of the health workforce by population, the Gini coefficient remained below 0.3, while for geographical allocation, it exceeded 0.4. CONCLUSIONS: This study analyzed the temporal trends and inequality of health-resource allocation at the hospital and primary health center levels in China, noting trends of improvements in the quantity and inequality in health workforce allocation from 2010 to 2021, suggesting the success of the government's efforts to advance healthcare reform since 2009. The allocation of health workforce based on population exhibits greater fairness compared to geographical distribution.

HBeAg induces neutrophils activation impairing NK cells function in patients with chronic hepatitis B.

BACKGROUND: The role of neutrophils in hepatitis B virus (HBV) infection has been a subject of debate due to their involvement in antiviral responses and immune regulation. This study aimed to elucidate the neutrophil characteristics in patients with chronic hepatitis B (CHB). METHODS: Through flow cytometry and ribonucleic acid-sequencing analysis, the phenotypes and counts of neutrophils were analyzed in patients with CHB. Moreover, the effects of HBeAg on neutrophils and the corresponding pattern recognition receptors were identified. Simultaneously, the cross-talk between neutrophils and natural killer (NK) cells was investigated. RESULTS: Neutrophils were activated in patients with CHB, characterized by higher expression levels of programmed death-ligand 1 (PD-L1), cluster of differentiation 86, and interleukin-8, and lower levels of CXC motif chemokine receptor (CXCR) 1 and CXCR2. Hepatitis B e antigen (HBeAg) partially induces neutrophil activation through the Toll-like receptor 2 (TLR2). A consistent upregulation of the TLR2 and HBeAg expression was observed in patients with CHB. Notably, the genes encoding molecules pivotal for NK-cell function upon NK receptor engagement enriched in neutrophils after HBeAg activation. The HBeAg-activated neutrophils demonstrated the ability to decrease the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in NK cells, while the PD-1 and PD-L1 pathways partially mediated the immunosuppression. CONCLUSIONS: The immunosuppression of neutrophils induced by HBeAg suggests a novel pathogenic mechanism contributing to immune tolerance in patients with CHB.

Treatment of swine manure by hydrothermal carbonization: The influential effect and preliminary mechanism of surfactants.

Treatment of swine manure by hydrothermal carbonization (HTC) with the aid of different surfactants was first explored in this study. PEG 400 (polyethylene glycol 400) and Tween 80 facilitated the formation of bio-oil. SLS (sodium lignosulfonate) and SDS (sodium dodecyl sulfate) promoted the formation of water-soluble matters/gases. Span 80 enhanced the formation of hydrochar, which resulted in a 50.19 % mass yield, 92.39 % energy yield, and a caloric value of 28.68 MJ/kg. The hydrochar obtained with Span 80 presented a similar combustion performance to raw swine manure and the best pyrolysis performance. The use of Span 80 promoted the transfer of degradation products to hydrochar, especially hydrophobic ester and ketone compounds. Notedly, Span 80 suppressed the synthesis of PAHs during the HTC process, which was reduced to 0.92 mg/kg. Furthermore, the hydrochar produced with Span 80 contained lower contents of heavy metals. On the whole, Span 80 has shown great potential in enhancing the HTC of swine manure. The acting mechanisms of surfactants in the HTC of swine manure included adsorption, dispersion, and electrostatics repulsion.

Association between longitudinal changes in body composition and the risk of kidney outcomes in participants with overweight/obesity and type 2 diabetes mellitus.

AIMS: To assess the relationship of longitudinal changes in fat mass (FM), lean mass (LM) and waist circumference (WC) with incident kidney outcomes in people with overweight/obesity and type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A total of 3927 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 from the Look AHEAD (Action for Health in Diabetes) trial were included. The primary outcome was kidney outcomes, defined as a decrease in eGFR of at least 40% from baseline at follow-up visit, or end-stage kidney disease. RESULTS: During a median follow-up of 8.0 years, 450 kidney outcomes were documented after the first 1 year. In the intensive lifestyle intervention (ILI) group, reductions in FM (per 10% decrease, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69-0.94) and WC (per 10% decrease, adjusted HR 0.72, 95% CI 0.59-0.88) from baseline to 1-year follow-up were significantly associated with a lower risk of kidney outcomes. The change in LM was not significantly associated with risk of kidney outcomes (per 10% decrease, adjusted HR 0.78, 95% CI 0.58-1.06). In the diabetes support and education group (control group), no significant association was found between changes in body composition and kidney outcomes. Similar results were observed for the 4-year changes in body composition. CONCLUSIONS: In this post hoc analysis of the Look AHEAD trial, longitudinal declines in FM and WC were associated with a lower risk of kidney outcomes in the ILI group in participants with overweight/obesity and T2DM.

Thermosensitive curcumin/silver/montmorillonite-F127 hydrogels with synergistic photodynamic/photothermal/silver ions antibacterial activity.

Bacterial infections and the emergence of super-resistant bacteria pose a significant risk to human health. Effective sterilization to prevent the development of bacterial drug resistance remains a challenge. Herein, curcumin/silver/montmorillonite (Cur/Ag/Mt) was prepared through a green chemical reduction method with montmorillonite as the carrier, curcumin as the reducing agent and the capping agent, and citric acid as the structure guide agent. Then, a novel dual light-responsive and thermosensitive Pluronic F127-based hydrogel (CAM-F) was prepared by encapsulating Cur/Ag/Mt within the F127 hydrogel. The Cur/Ag/Mt showed strong absorption in the near-infrared region that efficiently converts light into heat for photothermal therapy when the molar ratio of curcumin to silver nitrate was 2 : 1. Specifically, triangular silver nanoparticles reduced by curcumin were immobilized on the Mt layers, which could enhance photodynamic therapy by the metal-enhanced singlet oxygen and metal-enhanced fluorescence mechanisms. Upon combining 405 nm and 808 nm laser irradiation, the CAM-F hydrogel could simultaneously generate reactive oxygen species, increase the local temperature, and sustain the release of Ag+, thus displaying excellent bactericidal performance against Gram-negative and Gram-positive bacteria. The antibacterial rates of CAM-F hydrogels were 99.26 ± 0.95% and 99.95 ± 0.98% for Escherichia coli and Staphylococcus aureus, respectively. The findings suggest the potential of the CAM-F hydrogel as a stable, biologically safe, and broad-spectrum antimicrobial material. The thermosensitive CAM-F hydrogels for synergetic phototherapy may provide a promising strategy for solving clinical problems caused by pathogenic infections.

Association Between Rheumatoid Arthritis and Clonal Hematopoiesis: A Mendelian Randomization Study.

Immunity activation and inflammation are the main characteristics of rheumatoid arthritis and clonal hematopoiesis. However, it remains unclear whether rheumatoid arthritis increase the risk of clonal hematopoiesis. Here, a Mendelian randomization (MR) analysis was conduct to explore the causal effects of rheumatoid arthritis on clonal hematopoiesis. Summary statistics data of rheumatoid arthritis (13,838 cases and 33,742 controls) and clonal hematopoiesis (10,203 cases and 173,918 controls) derived from a genomewide association study were selected to analyze. We selected inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode to evaluate the causal effect of rheumatoid arthritis on clonal hematopoiesis. The two-sample MR analysis suggested a strong causal relationship between rheumatoid arthritis and clonal hematopoiesis by inverse-variance weighted (OR = 1.002311673, 95% CI [1.000110757, 1.004517433], p = .039706) and weighted median (OR = 1.002311673, 95% CI [1.000110757, 1.004517433], p = .039518447) methods. No significant pleiotropy or heterogeneity was found in the sensitivity analysis. These results supported a potentially causal relationship between rheumatoid arthritis and clonal hematopoiesis, and the exposure of rheumatoid arthritis increased the risks of clonal hematopoiesis. Our findings highlight the importance of how chronic inflammation and immune activation induced rheumatoid arthritis enhances the risks of clonal hematopoiesis, and that early intervention with rheumatoid arthritis patients might reduce the clonal hematopoiesis risks in rheumatoid arthritis patients. Moreover, our study provides clues for prediction of risk factors and potential mechanisms of clonal hematopoiesis.

Association between lung function and risk of microvascular diseases in patients with diabetes: A prospective cohort and Mendelian randomization study.

BACKGROUND AND AIMS: To investigate causal relationships of lung function with risks microvascular diseases among participants with diabetes, type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM), respectively, in prospective and Mendelian randomization (MR) study. METHODS AND RESULTS: 14,617 participants with diabetes and without microvascular diseases at baseline from the UK Biobank were included in the prospective analysis. Of these, 13,421 had T2DM and 1196 had T1DM. The linear MR analyses were conducted in the UK Biobank with 6838 cases of microvascular diseases and 10,755 controls. Lung function measurements included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The study outcome was microvascular diseases, a composite outcome including chronic kidney diseases, retinopathy and peripheral neuropathy. During a median follow-up of 12.1 years, 2668 new-onset microvascular diseases were recorded. FVC (%predicted) was inversely associated with the risk of new-onset microvascular diseases in participants with diabetes (Per SD increment, adjusted HR = 0.86; 95%CI:0.83-0.89), T2DM (Per SD increment, adjusted HR = 0.86; 95%CI:0.82-0.90) and T1DM (Per SD increment, adjusted HR = 0.87; 95%CI: 0.79-0.97), respectively. Similar results were found for FEV1 (%predicted). In MR analyses, genetically predicted FVC (adjusted RR = 0.55, 95%CI:0.39-0.77) and FEV1 (adjusted RR = 0.48, 95%CI:0.28-0.83) were both inversely associated with microvascular diseases in participants with T1DM. No significant association was found in those with T2DM. Similar findings were found for each component of microvascular diseases. CONCLUSION: There was a causal inverse association between lung function and risks of microvascular diseases in participants with T1DM, but not in those with T2DM.

Novel Hemodynamic, Vascular Lesion and Cytokine/Chemokine Differences Regarding Sex in a PAH Model.

Sex differences are recognized in pulmonary hypertension, however the progression of disease with regards to vascular lesion formation and circulating cytokines/chemokines is unknown. To determine whether vascular lesion formation, changes in hemodynamics and alterations in circulating chemokines/cytokines differ between male and female. We used a progressive model of PAH, SU/Hx and analyzed cohorts of male and female rats at timepoints suggested to indicate worsening disease. Our analysis included echocardiograpy for hemodynamics, morphometry, immunofluoresecence and chemokine/cytokine analysis of plasma at each time point in both sexes. We found that male rats had significantly increased Fulton index compared to females at each time point as well as increased medial artery thickening at 8-weeks PAH. Further, females exhibit fewer obliterative vascular lesions than males at our latest time point. Our data also show increased IL-4, GM-CSF, IL-10, and MIP-1 that are not observed in females, while females have increased RANTES and CXCL-10 not found in males. Males also have increased infiltrating macrophages in vascular lesions as compared to females. We found that development of progressive PAH in hemodynamics, morphology and chemokine/cytokine circulation differ significantly between males and females. These data suggest a macrophage driven pathology in males, while there may be T-cell protection from vascular damage in female PAH.

Perioperative Hypothermia in Elderly Patients During Pelvic Floor Reconstruction Surgery: An Observational Study.

INTRODUCTION AND HYPOTHESIS: The potential predictors of pelvic floor reconstruction surgery hypothermia remain unclear. This prospective cohort study was aimed at identifying these predictors and evaluating the outcomes associated with perioperative hypothermia. METHODS: Elderly patients undergoing pelvic floor reconstruction surgery were consecutively enrolled from April 2023 to September 2023. Perioperative temperature was measured at preoperative (T1), every 15 min after the start of anesthesia (T2), and 15 min postoperative (T3) using a temperature probe. Perioperative hypothermia was defined as a core temperature below 36°C at any point during the procedure. Multivariate logistic regression analysis was conducted to determine factors associated with perioperative hypothermia. RESULTS: A total of 229 patients were included in the study, with 50.7% experiencing hypothermia. Multivariate analysis revealed that the surgical method involving pelvic floor combined with laparoscopy, preoperative temperature < 36.5°C, anesthesia duration ≥ 120 min, and the high levels of anxiety were significantly associated with perioperative hypothermia. The predictive value of the multivariate model was 0.767 (95% CI, 0.706 to 0.828). CONCLUSIONS: This observational prospective study identified several predictive factors for perioperative hypothermia in elderly patients during pelvic floor reconstruction surgery. Strategies aimed at preventing perioperative hypothermia should target these factors. Further studies are required to assess the effectiveness of these strategies, specifically in elderly patients undergoing pelvic floor reconstruction surgery.