OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration （cmin） of voriconazole （VRZ） in patients with invasive fungal infection. METHODS The Cochrane Library， Embase， PubMed， Web of Science， China Biomedical Literature Database， CNKI， VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms and cmin of VRZ from inception to April 2024. After screening the literature， extracting data， and evaluating the quality of the literature， meta-analysis was performed using R 4.3.2 software. RESULTS A total of 21 studies with 2 454 patients were included. The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type， and the VRZ cmin of IM type was significantly lower than PM type （P＜0.01）. The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type， and that of CYP3A5 rs776746 CC type was significantly higher than TT type （P＜0.01）. The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types， and that of POR rs1057868 CT type was significantly lower than TT type （P＜0.01）. The VRZ cmin of ABCB1 rs1045642 CC type was significantly higher than TT type （P＜0.05）. The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type， and rs7643645 AA type was significantly higher than AG type （P＜0.05）. The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type， and the CT type was significantly lower than TT type （P＜0.01）. CONCLUSIONS Mutant alleles in CYP2C19， CYP2C9 rs1057910， CYP3A5 rs776746， POR rs10954732， ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration， and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration （cmin） of voriconazole （VRZ） in patients with invasive fungal infection. METHODS The Cochrane Library， Embase， PubMed， Web of Science， China Biomedical Literature Database， CNKI， VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms and cmin of VRZ from inception to April 2024. After screening the literature， extracting data， and evaluating the quality of the literature， meta-analysis was performed using R 4.3.2 software. RESULTS A total of 21 studies with 2 454 patients were included. The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type， and the VRZ cmin of IM type was significantly lower than PM type （P＜0.01）. The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type， and that of CYP3A5 rs776746 CC type was significantly higher than TT type （P＜0.01）. The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types， and that of POR rs1057868 CT type was significantly lower than TT type （P＜0.01）. The VRZ cmin of ABCB1 rs1045642 CC type was significantly higher than TT type （P＜0.05）. The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type， and rs7643645 AA type was significantly higher than AG type （P＜0.05）. The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type， and the CT type was significantly lower than TT type （P＜0.01）. CONCLUSIONS Mutant alleles in CYP2C19， CYP2C9 rs1057910， CYP3A5 rs776746， POR rs10954732， ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration， and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and hypertension are common metabolic disorders, both closely associated with insulin resistance (IR), suggesting potential shared pathological mechanisms. This study aims to investigate the mediating role of IR in the relationship between hypertension and NAFLD, and to evaluate the applicability and modeling value of various IR surrogate indices in predicting NAFLD risk. METHODS: A total of 280 976 individuals who underwent health examinations at the Health Management Center of the Third Xiangya Hospital of Central South University between August 2017 and December 2021 were included. NAFLD was diagnosed based on abdominal ultrasound findings, and hypertension was defined according to the criteria of the Chinese Guidelines for the Management of Hypertension. Demographic information, anthropometric indices, and biochemical parameters were collected, and multiple IR surrogate indices were constructed, including the triglyceride-glucose index (TyG) and its derivatives, as well as the metabolic score for insulin resistance (METS-IR). Group comparisons were performed between hypertensive and non-hypertensive participants, as well as between NAFLD and non-NAFLD participants. Pearson correlation analysis was applied to assess the associations of metabolic parameters and IR indices with NAFLD. Furthermore, mediation models were constructed to explore the mediating role of IR in the "hypertension-NAFLD" relationship. Finally, parametric models and machine learning algorithms were compared to evaluate their predictive performance and value in assessing NAFLD risk in this population. RESULTS: The prevalence of NAFLD was significantly higher in hypertensive individuals than in non-hypertensive participants (63.61% vs 33.79%, P<0.001), accompanied by elevated IR levels and adverse metabolic features. Correlation analysis and variable importance rankings across multiple models consistently identified TyG-waist circumference (TyG-WC) and METS-IR as the IR indices most strongly associated with NAFLD. In mediation analysis, the TyG-WC pathway explained 32.03% of the total effect, and the METS-IR pathway explained 17.02%. Interaction analysis showed that hypertension status may attenuate the mediating effect of IR (all interaction estimates were negative). In prediction model comparisons, the simplified model incorporating sex, age, WC, TyG-WC, and METS-IR demonstrated good performance in the test set. Logistic regression and its regularized form (LASSO regression) achieved an accuracy of 0.83, receiver operating characteristic (ROC)-area under the curve (AUC) of 0.91, and a Brier score of 0.12, comparable to ensemble models (random forest and XGBoost), with consistently stable performance across different algorithms. CONCLUSIONS IR plays a significant mediating role in the association between hypertension and NAFLD, with TyG-WC identified as a key indicator showing strong mechanistic relevance and predictive value. Risk prediction models based on IR surrogate indices demonstrate advantages in simplicity and interpretability, providing empirical support for the early screening and individualized prevention of NAFLD in the general population.
Humans ; Non-alcoholic Fatty Liver Disease/complications* ; Insulin Resistance ; Hypertension/epidemiology* ; Male ; Female ; Middle Aged ; Risk Factors ; Adult ; Machine Learning ; Triglycerides/blood*

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

To analyze the prevalence, genomic characteristics and clinical relevance of carbapenem-resistant bacteria in untreated hospital wastewater, and to provide a reference basis for in-hospital assessment of public health situation and prevention of cross-infection. In March 2023, untreated wastewater in the wastewater treatment station of the Second Affiliated Hospital of Soochow University and wastewater in the U-shaped wastewater pipes of the hand-washing sinks in 26 wards were collected, centrifuged and diluted, and the drug-resistant bacteria were isolated by using LB solid plates containing meropenem (2 μg/ml) for species identification, drug sensitivity analysis, carbapenenase gene PCR detection and whole genome sequencing. The genome sequence was identified for drug resistance genes. Retrospective research was used, combining multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis, to compare their homology with clinical isolates of the same quarter. The results showed that 56 carbapenem-resistant gram-negative bacteria were isolated from hospital wastewater, originating from 13 genera, of which 17 were isolated from the total hospital wastewater, with Aeromonas spp. as the most dominant genus (35.3%, 6/17), and 39 were isolated from the wastewater of 17 wards, with Pseudomonas spp. as the most dominant genus (30.8%, 12/39). All common wastewater isolates from our hospital were multidrug-resistant bacteria, with up to 100% resistant to some second-and third-generation cephalosporins. A total of 8 carbapenemase genes originated from wastewater isolates, including blaKPC, blaNDM, blaIMP, blaVIM, blaIND, blaOXA-58-like, blaOXA-48-like, and blaOXA-427-like. 39 wastewater isolates carried the carbapenemase genes, and the total wastewater of the hospital carried the highest isolation rate of blaKPC-2 bacteria (35.3%, 6/17) and the highest isolation rate of blaIMP-8 bacteria (31.8%, 7/22) were found in the wastewater from 26 wards. 14 wastewater isolates were found to carry both carbapenemase genes, with a total of 6 combinations. A new blaIMP-101 isoform was also identified for the first time. 4 wastewater isolates and 11 clinical isolates were screened for inclusion in the SNP analysis, in which only 15 SNPs differed between the two strains of ST11 Klebsiella pneumoniae of clinical and wastewater origin, which was highly homologous. In conclusion, the presence of multiple multi-drug resistant conditionally pathogenic bacteria in untreated hospital wastewater has the potential risk of spreading drug-resistant genes in the environment. The highly homologous Klebsiella pneumoniae isolated from hospital wastewater and clinics indicates the close association between hospital wastewater and clinical infections. Hospitals need to strengthen the monitoring of drug-resistant bacteria and drug-resistant genes in the wastewater environment, to prevent the widespread dissemination of drug-resistant bacteria and drug-resistant genes in hospital wastewater and to prevent nosocomial infections caused by drug-resistant bacteria in wastewater.

To analyze the prevalence, genomic characteristics and clinical relevance of carbapenem-resistant bacteria in untreated hospital wastewater, and to provide a reference basis for in-hospital assessment of public health situation and prevention of cross-infection. In March 2023, untreated wastewater in the wastewater treatment station of the Second Affiliated Hospital of Soochow University and wastewater in the U-shaped wastewater pipes of the hand-washing sinks in 26 wards were collected, centrifuged and diluted, and the drug-resistant bacteria were isolated by using LB solid plates containing meropenem (2 μg/ml) for species identification, drug sensitivity analysis, carbapenenase gene PCR detection and whole genome sequencing. The genome sequence was identified for drug resistance genes. Retrospective research was used, combining multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis, to compare their homology with clinical isolates of the same quarter. The results showed that 56 carbapenem-resistant gram-negative bacteria were isolated from hospital wastewater, originating from 13 genera, of which 17 were isolated from the total hospital wastewater, with Aeromonas spp. as the most dominant genus (35.3%, 6/17), and 39 were isolated from the wastewater of 17 wards, with Pseudomonas spp. as the most dominant genus (30.8%, 12/39). All common wastewater isolates from our hospital were multidrug-resistant bacteria, with up to 100% resistant to some second-and third-generation cephalosporins. A total of 8 carbapenemase genes originated from wastewater isolates, including blaKPC, blaNDM, blaIMP, blaVIM, blaIND, blaOXA-58-like, blaOXA-48-like, and blaOXA-427-like. 39 wastewater isolates carried the carbapenemase genes, and the total wastewater of the hospital carried the highest isolation rate of blaKPC-2 bacteria (35.3%, 6/17) and the highest isolation rate of blaIMP-8 bacteria (31.8%, 7/22) were found in the wastewater from 26 wards. 14 wastewater isolates were found to carry both carbapenemase genes, with a total of 6 combinations. A new blaIMP-101 isoform was also identified for the first time. 4 wastewater isolates and 11 clinical isolates were screened for inclusion in the SNP analysis, in which only 15 SNPs differed between the two strains of ST11 Klebsiella pneumoniae of clinical and wastewater origin, which was highly homologous. In conclusion, the presence of multiple multi-drug resistant conditionally pathogenic bacteria in untreated hospital wastewater has the potential risk of spreading drug-resistant genes in the environment. The highly homologous Klebsiella pneumoniae isolated from hospital wastewater and clinics indicates the close association between hospital wastewater and clinical infections. Hospitals need to strengthen the monitoring of drug-resistant bacteria and drug-resistant genes in the wastewater environment, to prevent the widespread dissemination of drug-resistant bacteria and drug-resistant genes in hospital wastewater and to prevent nosocomial infections caused by drug-resistant bacteria in wastewater.

  Objective  To analyze the current status of the development of adaptation guidelines in China, as well as their methodological quality and the reporting quality, in order to provide reference for the development of adaptation guidelines.  Methods  We searched and collected adaptation guidelines led by Chinese researchers or institutions from 2015 to 2023 from four electronic databases, China National Knowledge Infrastructure, WanFang Data Knowledge Service Platform, SinoMed and PubMed, extracted the basic information of the adapted guidelines, and assessed their methodological quality and reporting quality using the Appraisal of Guidelines for REsearch and Evaluation (AGREE) Ⅱ and RIGHT-Ad@pt tools.  Results  A total of 14 adaptation guidelines were included, mainly focusing on nursing (42.9%, 6/14), with the most frequently used adaptation method of ADAPTE (71.4%, 10/14), and with reference to pre-existing guidelines mainly from the United States, the United Kingdom, and international organizations. Assessment by the AGREE Ⅱ tool showed that the average methodological quality score of the adapted guidelines was 36.6%. The scores were relatively high in the domains of clarity of expression and rigor of formulation (44.4% and 54.9%), and lowest in the domain of applicability (15.3%). The results of the RIGHT-Ad@pt tool showed that the reporting quality of the adaptation guidelines was relatively good, with the highest reporting rate of 91.2% and the lowest of 35.3%, and the reporting rates of seven articles were higher than 70%.  Conclusions  Adaptation guidelines in China are still in their infancy, with a relatively small number and mainly focusing on the nursing field. The most commonly used adaptation method is the ADAPTE method. The methodological quality and reporting quality of adaptation guidelines need to be further improved, and more research should be conducted on the specific conditions and timing of adaptation guidelines development.

Objective:To identify and characterize one Yokenella regensburgei strain(designated as CXLZQ123) isolated from a case of perionychial abscess. Methods:Strain CXLZQ123 was isolated from a patient with periungual abscess at the Dermatology Department of San County Central Hospital in June 2, 2023. The strain was initially identified through morphological and biochemical tests, followed by mass spectrometry identification, 16S rRNA sequencing and whole-genome sequencing. MEGA 11.0 was used to compare and analyze the strain′s genetic relationship with relevant species in GenBank, and a phylogenetic tree was constructed based on genetic distance to analyze its genetic evolution. Meanwhile, the average nucleotide identity between its genome and similar strains were compared.Results:The strain was identified as a Gram-negative rod. MicroScan WalkAway biochemical tests indicated that the strain was either Yokenella regensburgei (91.47%) or Hafnia alvei (8.53%). MALDI-TOF mass spectrometry confirmed it as Yokenella regensburgei. Based on 16S rRNA gene sequence analysis, the strain showed the highest similarity(99.37%) to CIP 105435 (sequence number NR_104934.1). The 16S rRNA gene sequence of the isolated strain Yokenella regensburgei was submitted to the National Center for Biotechnology Information (NCBI) with the GenBank sequence number of OR230248.1. The whole-genome of CXLZQ123 were sequenced and uploaded (NCBI, SRA sequence number: SRR26510420). The average nucleotide identity between CXLZQ123 and Yokenella regensburgei strains W13 and UU2206353 were 98.82% and 99.04%, respectively. Conclusions:Through morphological observation, biochemical identification, mass spectrometry identification, 16S rRNA and whole-genome sequencing, this pathogenic strain is identified as Yokenella regensburgei. This rare bacterium is sensitive to most detected antibiotics. This study provides diagnostic and treatment experience for Yokenella regensburgei-related infections.