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Abstract Background The rise of antibiotic resistance has become a critical global health concern, resulting in numerous fatalities annually. Among resistant pathogens, methicillin-resistant Staphylococcus aureus (MRSA) poses a particularly severe and expanding threat. However, there is a lack of comprehensive studies on the prevalence, patterns, and contributing factors of MRSA resistance within mainland China. Methods In this study, the data of MRSA antimicrobial resistance in 31 provinces from 2014 to 2021 were obtained from the China Antimicrobial Resistance Surveillance System (CARSS). Environment and medical care data were obtained either from the National Bureau of Statistics (NBS) database or the National Ministry of Ecology and Environment (NMEE). Multiple linear regression and restricted cubic spline (RCS) was used to explore the potential influencing factors of MRSA antibiotic resistance rate (AMR). Results Significant positive associations were identified between MRSA AMR and various factors, including cadmium pollution, soybean and poultry production, and oil consumption. Conversely, an inverse J-shaped relationship was observed between tap water coverage and MRSA resistance. Other noteworthy correlations included the effects of corn and pork production, as well as antibiotic use intensity. Our predictive model explained 52.7% of the variability in MRSA AMR, demonstrating strong predictive capability. Conclusions This study highlights the significant role of environmental, agricultural, and healthcare factors in influencing MRSA AMR in China. The findings emphasize the need for integrated strategies addressing regional environmental and healthcare quality in combating antibiotic resistance. Extending this research globally could enhance understanding of MRSA resistance dynamics on a broader scale. Graphical Abstract

BackgroundThe concurrent administration of tacrolimus and voriconazole in kidney transplant recipients can lead to drug interactions, potentially resulting in severe adverse reactions. This study aimed to establish a robust population pharmacokinetic model to explore the interaction between tacrolimus and voriconazole in greater depth.MethodsTacrolimus blood samples and laboratory data were prospectively collected from eligible patients enrolled between April 2023 and April 2024, following predefined inclusion and exclusion criteria. Using Phoenix (version 8.1), a pharmacokinetic prediction model was developed. Model performance was assessed using model fitting plots, bootstrap analysis, and visual predictive checks (VPC).ResultsThis study ultimately included 51 eligible patients, with a total of 281 blood samples collected. Analysis revealed a significant negative correlation between voriconazole concentration (Cvrc) and tacrolimus volume of clearance rate (CL), a significant positive correlation between platelets (PLT) and tacrolimus clearance (CL), and a significant negative correlation between blood cells (RBC) and tacrolimus clearance (CL).ConclusionThis study successfully established a population pharmacokinetic model for renal transplant patients concurrently receiving tacrolimus and voriconazole. The model demonstrated good predictive performance and offers valuable insights to clinicians for optimizing tacrolimus dosing in this patient population.

ObjectivesSignificant increase in tacrolimus exposure was observed during co-administration with voriconazole, and no population pharmacokinetic model exists for tacrolimus in renal transplant recipients receiving voriconazole. To achieve target tacrolimus concentrations, an optimal dosage regimen is required. This study aims to develop individualized dosing parameters through population pharmacokinetic analysis and simulate tacrolimus concentrations under different dosage regimens.MethodsWe conducted a retrospective study of renal transplant recipients who were hospitalized at the Second Xiangya Hospital of Central South University between January 2016 and March 2021. Subsequently, pharmacokinetic analysis and Monte Carlo simulation were employed for further analysis.ResultsNineteen eligible patients receiving tacrolimus and voriconazole co-therapy were included in the study. We collected 167 blood samples and developed a one-compartment model with first-order absorption and elimination to describe the pharmacokinetic properties of tacrolimus. The final typical values for tacrolimus elimination rate constant (Ka), apparent volume of distribution (V/F), and apparent oral clearance (CL/F) were 8.39 h−1, 2690 L, and 42.87 L/h, respectively. Key covariates in the final model included voriconazole concentration and serum creatinine. Patients with higher voriconazole concentration had lower tacrolimus CL/F and V/F. In addition, higher serum creatinine levels were associated with lower tacrolimus CL/F.ConclusionOur findings suggest that clinicians can predict tacrolimus concentration and estimate optimal tacrolimus dosage based on voriconazole concentration and serum creatinine. The effect of voriconazole concentration on tacrolimus concentration was more significant than serum creatinine. These findings may inform clinical decision-making in the management of tacrolimus and voriconazole therapy in solid organ transplant recipients.

Abstract Background Bacterial drug resistance represents a significant global concern, with vancomycin-resistant Enterococcus faecalis posing a particularly grave threat to contemporary healthcare systems. This study aims to reveal the reasons for the prevalence of VRE in China. Methods This study collected data from the China Antimicrobial Resistance Detection System, China Statistical Yearbook, and China Meteorological Network. The collected data are meticulously organized and subjected to both single-factor and multi-factor analyses. An accurate multiple linear regression model was developed by utilizing this comprehensive dataset. Results Single-factor analysis revealed significant regional variations in the resistance rate of vancomycin-resistant Enterococcus faecalis (P = 0.003). Specifically, there were noteworthy disparities observed between regions experiencing temperate and monsoon climates (P = 0.029; P = 0.005). Furthermore, multi-factor regression analysis demonstrated a negative correlation between the drug resistance rate and both rainfall and rGDP, while a positive correlation was observed with nPI. Conclusion We successfully established a prediction model for the VRE and found that the resistance rate was low in areas with high rainfall and high per capita economic income, but high in areas with many specialized public health institutions. This is critical for public health strategies and helps policymakers and healthcare practitioners tailor antibiotic resistance approaches to local geography, meteorology, economic conditions.

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes severe inflammatory response, respiratory disease and sow reproductive failure. Quercetin is among the widely occurring polypheno found abundantly in nature. Quercetin has anti‐inflammatory, anti‐oxidative and anti‐viral properties. Objectives This study aimed to explore the effect and mechanism of quercetin on PRRSV‐induced inflammation in MARC‐145 cells. Methods Observing the cytopathic effect and measurements of inflammatory markers in MARC‐145 cells collectively demonstrate that quercetin elicits a curative effect on PRRSV‐induced inflammation. Liquid chromatography–mass spectrometry was further used for a non‐targeted metabolic analysis of the role of quercetin in the metabolic regulation of PRRSV inflammation in MARC‐145 cells. Results It was shown that quercetin attenuated PRRSV‐induced cytopathy in MARC‐145 cells. Quercetin treatment inhibited PRRSV replication in MARC‐145 cells in a dose‐dependent manner. We also found that quercetin inhibited PRRSV‐induced mRNA expression and secretion levels of tumour necrosis factor‐α, interleukin 1β and interleukin 6. Metabolomics analysis revealed that quercetin ameliorated PRRSV‐induced inflammation. Pathway analysis results revealed that PRRSV‐induced pathways including arachidonic acid metabolism, linoleic acid, glycerophospholipid and alanine, aspartate and glutamate metabolism were suppressed by quercetin. Moreover, we confirmed that quercetin inhibited the activation of NF‐κB/p65 pathway, probably by attenuating PLA2, ALOX and COX mRNA expression. Conclusions These results provide a crucial insight into the molecular mechanism of quercetin in alleviating PRRSV‐induced inflammation.

AIM: To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification. METHODS: This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit. RESULTS: The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion. CONCLUSION: Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is.

AIM: To demonstrate local dry vitrectomy combined with segmental scleral buckling and viscoelastic tamponade for the treatment of partial rhegmatogenous retinal detachment (RRD) with local vitreous traction in patients at high-risk for proliferative vitreoretinopathy (PVR). METHODS: Eleven eyes of 11 patients were retrospectively studied, including 5 retinal dialysis and 6 retinal detachment (RD; 5 eyes with peripheral retinal hole and 1 eye with giant tear). All patients exhibited partial RD and local vitreous traction. Combined local dry vitrectomy without conventional infusion and segmental scleral buckling was performed. Viscoelastic fluid was injected into the vitreous cavity if needed. Demographic information, preoperative and post-operative complications, and outcomes were recorded. RESULTS: The mean age of the patients at presentation was 26.55±13.52y. All 11 patients obtained retinal reattachment after a single surgical intervention. Postoperative visual acuities were improved or remained stable in all patients. None of them developed complications, except for temporary mildly increased intraocular pressure in 3 cases. CONCLUSION: Combined local dry vitrectomy and segmental scleral buckling are effective for patients of RRD with local vitreous traction. The technique avoids many complications associated with regular surgery and was minimally invasive to both the external and internal eye.

Color-tunable organic solid-state luminescent materials have received increasing attention owing to their potential applications in displays, imaging, encryption, etc. To provide more information about structure-packing-property relationship of color-tunable organic luminophores, molecules with definite structures and explicit molecular packing are highly desired. In this work, we present an strategy to realize color-tunable luminescence by using the organic molecule 1-(4-carboxyphenyl)-4,4′-bipyridinium (CPB) as building block to construct two kinds of polymorphs by altering molecular conformation and packing modes. The color-tunable emission and relationship between the molecular packing fashion and bulk optical properties are reported. The findings open the opportunity for the development of novel color-tunable luminophores.

Tacrolimus is an immunosuppressant with a narrow therapeutic window. Tacrolimus exposure increased significantly during voriconazole co-therapy. The magnitude of this interaction is highly variable, but it is hard to predict quantitatively. We conducted a study on 91 kidney transplantation recipients with voriconazole co-therapy. Furthermore, 1701 tacrolimus concentration data were collected. Standard concentration adjusted by tacrolimus daily dose (C/D) and weight-adjusted standard concentration (CDW) increased to 6 times higher during voriconazole co-therapy. C/D and CDW increased with voriconazole concentration. Patients with the genotype of CYP3A5 *3/*3 and CYP2C19 *2/*2 or *2/*3 were more variable at the same voriconazole concentration level. The final prediction model could explain 54.27% of the variation in C/D and 51.11% of the variation in CDW. In conclusion, voriconazole was the main factor causing C/D and CDW variation, and the effect intensity should be quantitative by its concentration. Kidney transplant recipients with CYP3A5 genotype of *3/*3 and CYP2C19 genotype of *2/*2 and *2/*3 should be given more attention during voriconazole co-therapy. The prediction model established in this study may help to reduce the occurrence of rejection.

Voriconazole is a triazole antifungal agent commonly used for the treatment and prevention of invasive aspergillosis (IA). However, the study of voriconazole's use in children is limited. The present study was performed to explore maintenance dose to optimize voriconazole dosage in children and the factors affecting voriconazole trough concentration. This is a non-interventional retrospective clinical study conducted from 1 January 2016 to 31 December 2020. The study finally included 94 children with 145 voriconazole trough concentrations. The probability of achieving a targeted concentration of 1.0–5.5 µg/mL with empiric dosing increased from 43 (45.3%) to 78 (53.8%) after the TDM-guided adjustment. To achieve targeted concentration, the overall target maintenance dose for the age group of less than 2, 2 to 6, 6 to 12, and 12 to 18 years old was approximately 5.71, 6.67, 5.08 and 3.31 mg·kg−1/12 h, respectively (p < 0.001). Final multivariate analysis found that weight (p = 0.019), dose before sampling (p < 0.001), direct bilirubin (p < 0.001), urea nitrogen (p = 0.038) and phenotypes of CYP2C19 were influencing factors of voriconazole trough concentration. These factors can explain 36.2% of the variability in voriconazole trough concentration. Conclusion: In pediatric patients, voriconazole maintenance doses under the target concentration tend to be lower than the drug label recommended, but this still needs to be further studied. Age, body weight, dose, direct bilirubin, urea nitrogen and phenotypes of CYP2C19 were found to be influencing factors of voriconazole concentration in Chinese children. The influence of these factors should be taken into consideration during voriconazole use.

AIM: To reveal age-related aqueous cytokine changes in human aqueous humor. METHODS: Aqueous humor was collected from 12 young children (3-6.5 years old) and 71 healthy adults (22-106 years old) with cataract but without other systemic or ocular disorders. Levels of 22 cytokines, chemokines and vascular endothelial growth factor (VEGF) were measured and analyzed. RESULTS: The following proteins showed significant increase from childhood to adult: interferon-gamma (IFN-γ), interleukin (IL)-13, IL-6, IL-12(p70), IL-10, CCL2, CCL3, CCL4, CXCL8, CXCL9, CXCL10, IFN-α2 and VEGF (all P0.5). The strength of correlation between aging and CCL4 were fair (r=0.398). The concentrations of IL-2, IL-4, IL-5, IL-1β and TNF-α were low in both groups. CONCLUSION: From childhood to adult, the immunological milieu of the anterior chamber become more pro-inflammatory and pro-angiogenic. Such changes may represent the parainflammation state of the human eye.

Background: Cells respond to DNA damage by activating the phosphatidylinositol-3 kinase-related kinases, p53 and other pathways to promote cell cycle arrest, apoptosis, and/or DNA repair. Here we report that protein palmitoylation, a modification carried out by protein acyltransferases with zinc-finger and Asp-His-His-Cys domains (zDHHC), is required for proper DNA damage responses. Results: Inhibition of protein palmitoylation compromised DNA damage-induced activation of Atm, induction and activation of p53, cell cycle arrest at G2/M phase, and DNA damage foci assembly/disassembly in primary mouse embryonic fibroblasts. Furthermore, knockout of zDHHC16, a palmitoyltransferase gene identified as an interacting protein for c-Abl, a non-receptor tyrosine kinase involved in DNA damage response, reproduced most of the defects in DNA damage responses produced by the inhibition of protein palmitoylation. Conclusions: Our results revealed critical roles for protein palmitoylation and palmitoyltransferase zDHHC16 in early stages of DNA damage responses and in the regulation of Atm activation. [ABSTRACT FROM AUTHOR]

The effects of Bi flux and pressure of AsH3 on Bi incorporation, surface morphology and optical properties of InGaAsBi grown by gas source molecular beam epitaxy are studied. It is found that using relatively low pressure of AsH3 and high Bi flux can strengthen the effect on the incorporation of Bi and increase its content linearly with Bi flux until it nearly reaches a saturation value. The result from Rutherford backscattering spectroscopy (RBS) confirms that the Bi incorporation can increase up to 1.13%. By adjusting Bi and As flux, we could improve the surface morphology of InGaAsBi sample. Room temperature photoluminescence shows strong and broad light emission at energy levels much smaller than the InGaAs bandgap. [ABSTRACT FROM AUTHOR]