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.

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.

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.

Objective: To explore the effects of high-altitude hypoxia on thyroid hormone(TH) synthesis by quasi-targeted metabolomics technology. Methods: Twenty SPF male SD rats were randomly divided into Control group and Hypoxia group. An acute hypoxia injury model was established in SD rats by simulating hypoxia stress in a hypobaric oxygen chamber at an altitude of 6 km for 48 hours. The body weight, arterial oxygen partial pressure(PaO2) and blood oxygen saturation(SaO2) were detected. KEGG enrichment analysis was performed after the metabolites in the blood of two groups were detected by quasi-targeted metabolomics technology. The expression levels of sodium iodide symporter(NIS), thyroid peroxidase(TPO) and thyroglobulin(TG) were detected by RT-PCR and Western blot in TH synthesis pathway. The content of serum thyroxine(T4) and the expression levels of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) were detected by ELISA. The expression levels of toll-like receptors-4(TLR-4), interleukin-6(IL-6), nuclear factor-κB/p65(NF-κB/p65) and tumor necrosis factor-α(TNF-α) were detected by RT-PCR, Western blot and ELISA. The expression levels of Pro apoptotic protein Bcl-2 associated X protein(Bax) and inhibitor of apoptosis protein B-cell lymphoma/leukemia-2(Bcl-2) were detected by RT-PCR and Western blot in rats thyroid tissue. Results: Compared with the Control group, the body weight, PaO2and SaO2of rats in the Hypoxia group significantly decreased(P<0.01). The differential metabolites in arterial serum of hypoxia group rats were significantly enriched in the TH synthesis pathway, and the content of the pathway end product T4decreased significantly(P<0.01). In addition, the mRNA and protein expression levels of NIS, TPO, TG in rats thyroid tissue significantly decreased(P<0.05). The ELISA validation results showed that the changes of T4content were completely consistent with the above results. Compared with the Control group, the enzyme activities of SOD and GSH-Px in the serum of rats in the hypoxia group decreased, while the content of MDA increased(P<0.01); the mRNA, protein expression levels and contents of TLR-4, IL-6, NF-κ B/p65, TNF-α significantly increased(P<0.05), while the mRNA and protein expression levels of Bax in thyroid tissue significantly increased, Bcl-2 significantly decreased(P<0.05). Conclusion Hypoxia stress at high altitude leads to apoptosis of thyroid follicular epithelial cells by promoting oxidative stress and inflammatory response, which effects thyroid function and ultimately reduces thyroid hormone synthesis.

Objective To investigate the virulence and drug resistance characteristics of diarrheagenic Escherichia coli isolated from patients with infectious diarrhea in our hospital.Methods The preliminary identification of microbes was carried out by the VITEK-MS microbial mass spectrometry detection system and virulence genes were detected by the multiplex real-time PCR.Five types of diarrhea-genic Escherichia coli(DEC)clinically isolated from patients with infectious diarrhea in our hospital were identified.The drug resist-ance characteristics of DEC strains were detected by the microbroth dilution and E-test.The drug-resistant molecular characteristics were analyzed by the next-generation sequencing and bioinformatics.The Fisher exact probability method was used for statistical analy-sis.Results The detection rate of DEC in our hospital was 11.9%,with enteroaggregative E.coli(EAEC)accounting for 37.5%,a-typical enteropathogenic Escherichia coli(EPEC)accounting for 34.38%,enterotoxigenic E.coli(ETEC)accounting for 25.0%,and enteroinvasive E.coli(EIEC)accounting for 3.12%.None of enterohemorrhagic E.coli(EHEC)strain was detected.The resistance rates of 32 DEC strains to ampicillin,tetracycline,and trimethoprim/sulfamethoxazole were 53.12%,43.75%,and 37.5%,respec-tively.ESBLs(+)strains accounted for 18.75%,and the detection rate of multidrug-resistant strains was 83.83%,significantly higher than that of ESBLs(-)strains(P=0.042).A total of 25 ST genotypes were obtained from 32 DEC strains.The dominant genotypes were ST10(4 strains,12.5%),followed by ST28(2 strains,6.25%),ST31(2 strains,6.25%),ST3153(2 strains,6.25%),and the other 21 genotypes(1 strain,3.13%).One carbapenem resistant strain carrying the blaNDM-1 gene was detected in EAEC.Conclu-sion Four virulence genes such as aggR,pic,astA,and eae,are more common in the DEC of patients with infectious diarrhea in our hospital,with EAEC and EPEC as the main subtypes.The genotypes are highly polymorphic,and multidrug-resistant strains have been detected.

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.

Objective:To assess the efficacy of a novel spatial-temporal polyp detection system in colonoscopy.Methods:This research was a retrospective comparative study. Eight hundred and thirty-three participants who underwent computer-aided detection (CADe) colonoscopy at the First Medical Center of Chinese PLA General Hospital between March and June 2023 were enrolled to the experimental group, while 770 individuals who received conventional colonoscopy from March to June 2022, in the identical operation room were to the control group. The primary outcome was the adenoma detection rate (ADR), and the secondary outcomes were the polyp detection rate (PDR), adenomas per colonoscopy (APC), and polyps per colonoscopy (PPC).Results:The ADR [29.3% (244/833) VS 21.7% (167/770), χ2=12.133, P<0.001] and PDR [47.9% (399/833) VS 37.9% (292/770), χ2=16.241, P<0.001] were significantly higher in the experimental group than those in the control group. Adenomas ≤5 mm [23.5% (196/833) VS 16.1% (124/770), χ2=13.808, P<0.001] and flat-type adenomas [15.1% (126/833) VS 7.3% (56/770), χ2=24.519, P<0.001] were detected in a significantly higher proportion of subjects in the experimental group than those in the control group. There were significant difference in APC [0 (0,1) VS 0 (0,1), Z=-3.698, P<0.001] and PPC [0 (0,1) VS 0 (0,1), Z=-4.424, P<0.001] between the experimental and control groups. The use of CADe system significantly increased both ADR [29.5% (167/566) VS 18.9% (89/472), χ2=15.709, P<0.001] and PDR [47.3% (268/566) VS 33.3% (157/472), χ2=21.123, P<0.001] in junior endoscopists. However, in senior endoscopists, there was no statistical significant difference in ADR [28.8% (77/267) VS 26.2% (78/298), χ2=0.502, P=0.479] or PDR [49.1% (131/267) VS 45.3% (135/298), χ2=0.800, P=0.371] with or without CADe system. Conclusion:The use of CADe system significantly increases overall polyp and adenoma detection in clinical practice, especially in the detection of diminutive and flat-type lesions. Junior endoscopists gain greater advantages from the use of CADe system than their senior peers.