Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:To compare the clinical characteristics and laboratory findings between elderly rheumatoid arthritis(ERA)with those of non-elderly rheumatoid arthritis(NERA)patients.Methods:A cross-sectional study was conducted.The study collected laboratory indicators of 1, 286 ERA and 3, 211 NERA patients admitted to the Affiliated Hospital of Zunyi Medical University between January 2015 and December 2022, including inflammatory indicators, complete blood count, liver/kidney function tests, blood lipid, and glycated hemoglobin(HbA 1c), etc. Results:Erythrocyte sedimentation rate, high-sensitivity C-reactive protein and rheumatoid factor in ERA patients were higher than those in NERA patients( t=13.940, 8.453, 3.400, all P<0.001). Hemoglobin, red blood cell count, red blood cell distribution width, albumin and total protein in ERA patients were lower than those in NERA patients( t=2.380, 6.546, 1.954, 12.800, 10.490, all P<0.05). The levels of aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, total bile acid, globulin, lactate dehydrogenase, creatinine and urea nitrogen in ERA patients were higher than those in NERA patients( t=3.366, 3.422, 2.760, 4.520, 3.676, Z=8.678, t=10.630, 17.640, all P<0.05). The levels of uric acid, alanine aminotransferase, total cholesterol, triglyceride, blood glucose and HbA 1c in female ERA patients were higher than those in NERA group( t=6.009, 1.100, 2.111, 3.954, 4.262, 2.667, all P<0.05). Decreased RBC, ALB, TP, GLB( OR=0.279, 95% CI: 0.133-0.582; OR=0.867, 95% CI: 0.809-0.930; OR=0.948, 95% CI: 0.903-0.996; OR=0.817, 95% CI: 0.798-0.833), and increased ALT, AST, Scr, BUN, LDL-C and TC( OR=1.013, 95% CI: 0.997-1.018; OR=1.046, 95% CI: 1.015-1.079; OR=1.026, 95% CI: 1.005-1.047; OR=1.034, 95% CI: 1.019-1.051; OR=1.373, 95% CI: 1.088-1.733; OR=1.266, 95% CI: 1.022-1.569)were independent influencing factors of ERA. Conclusions:ERA patients exhibit elevated inflammatory markers and are more prone to anemia, liver and kidney function damage, and malnutrition.Furthermore, female ERA patients are more likely to have abnormal uric acid, alanine aminotransferase, blood lipids, and blood glucose.

OBJECTIVES: To investigate the effect of interferon-λ1 (IFN-λ1) on glucocorticoid (GC) resistance in human bronchial epithelial cells (HBECs) stimulated by respiratory syncytial virus (RSV). METHODS: HBECs were divided into five groups: control, dexamethasone, IFN-λ1, RSV, and RSV+IFN-λ1. CCK-8 assay was used to measure the effect of different concentrations of IFN-λ1 on the viability of HBECs, and the sensitivity of HBECs to dexamethasone was measured in each group. Quantitative real-time PCR was used to measure the mRNA expression levels of p38 mitogen-activated protein kinase (p38 MAPK), glucocorticoid receptor (GR), and MAPK phosphatase-1 (MKP-1). Western blot was used to measure the protein expression level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic ratio of GR was calculated. RESULTS: At 24 and 72 hours, the proliferation activity of HBECs increased with the increase in IFN-λ1 concentration in a dose- and time-dependent manner (P˂0.05). Compared with the RSV group, the RSV+IFN-λ1 group had significant reductions in the half-maximal inhibitory concentration of dexamethasone and the mRNA expression level of p38 MAPK (P<0.05), as well as significant increases in the mRNA expression levels of GR and MKP-1, the level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic GR ratio (P<0.05). CONCLUSIONS IFN-λ1 can inhibit the p38 MAPK pathway by upregulating MKP-1, promote the nuclear translocation of GR, and thus ameliorate GC resistance in HBECs.
Humans ; p38 Mitogen-Activated Protein Kinases/genetics* ; Glucocorticoids/pharmacology* ; Receptors, Glucocorticoid/analysis* ; Dual Specificity Phosphatase 1/physiology* ; Dexamethasone/pharmacology* ; Drug Resistance/drug effects* ; Respiratory Syncytial Viruses ; Interferons/pharmacology* ; MAP Kinase Signaling System/drug effects* ; Epithelial Cells/drug effects* ; Signal Transduction/drug effects* ; Cells, Cultured

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

By using a strategy of leveraging the ability of metal-organic frameworks(MOFs)materials to precisely regulate the spatial orientation of cyclodextrins(CD),a polystyrene-modified γ-cyclodextrin metal-organic frameworks(PS-CD-MOFs)capillary coating was established and applied to the chiral separation of amino acids in open-tubular capillary electrochromatography(OT-CEC)based on the excellent film-forming property of polystyrene(PS).Characterization results by Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD)indicated that PS was successfully grafted onto the surface of CD-MOFs.The modification significantly improved the structural stability and thermal stability of CD-MOFs while maintaining the integrity of the MOFs.The PS-CD-MOFs coated capillary electrophoresis system exhibited excellent performance in separating dansylated amino acid enantiomers(Dns-D,L-AAs).Specifically,under the optimal separation conditions(Sodium dodecyl sulfate/boric acid buffer system,20 cm capillary,and 10 kV effective voltage),good separation was achieved for D,L-methionine(D,L-Met)and D,L-serine(D,L-Ser).Further quantitative analysis showed that Dns-D,L-Met presented a good linear relationship in the concentration range of 10.0-1500.0 μmol/L,with a correlation coefficient close to 0.998,demonstrating high sensitivity and repeatability.Not only did it overcome the problem that traditional CD(used as additives in capillary electrophoresis)could not precisely control the spatial orientation of chiral resolvents,but also it solved the issues of insufficient stability and bonding amount of CD-MOFs coatings by utilizing the excellent film-forming property of polymers on the inner wall of capillaries.This study provided an efficient and controllable new strategy for construction of chiral separation stationary phases.

OBJECTIVE: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. METHODS: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. RESULTS: Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. CONCLUSION Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis. Please cite this article as: Feng CY, Cai CS, Shi XQ, Zhang ZJ, Su D, Qiu YQ. Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma. J Integr Med. 2025; 23(1): 79-91.
Humans ; MicroRNAs/genetics* ; Liver Neoplasms/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Mitophagy/drug effects* ; Resveratrol/pharmacology* ; Animals ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Hep G2 Cells ; Mice ; Disease Progression ; Mice, Inbred BALB C

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:To compare the clinical characteristics and laboratory findings between elderly rheumatoid arthritis(ERA)with those of non-elderly rheumatoid arthritis(NERA)patients.Methods:A cross-sectional study was conducted.The study collected laboratory indicators of 1, 286 ERA and 3, 211 NERA patients admitted to the Affiliated Hospital of Zunyi Medical University between January 2015 and December 2022, including inflammatory indicators, complete blood count, liver/kidney function tests, blood lipid, and glycated hemoglobin(HbA 1c), etc. Results:Erythrocyte sedimentation rate, high-sensitivity C-reactive protein and rheumatoid factor in ERA patients were higher than those in NERA patients( t=13.940, 8.453, 3.400, all P<0.001). Hemoglobin, red blood cell count, red blood cell distribution width, albumin and total protein in ERA patients were lower than those in NERA patients( t=2.380, 6.546, 1.954, 12.800, 10.490, all P<0.05). The levels of aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, total bile acid, globulin, lactate dehydrogenase, creatinine and urea nitrogen in ERA patients were higher than those in NERA patients( t=3.366, 3.422, 2.760, 4.520, 3.676, Z=8.678, t=10.630, 17.640, all P<0.05). The levels of uric acid, alanine aminotransferase, total cholesterol, triglyceride, blood glucose and HbA 1c in female ERA patients were higher than those in NERA group( t=6.009, 1.100, 2.111, 3.954, 4.262, 2.667, all P<0.05). Decreased RBC, ALB, TP, GLB( OR=0.279, 95% CI: 0.133-0.582; OR=0.867, 95% CI: 0.809-0.930; OR=0.948, 95% CI: 0.903-0.996; OR=0.817, 95% CI: 0.798-0.833), and increased ALT, AST, Scr, BUN, LDL-C and TC( OR=1.013, 95% CI: 0.997-1.018; OR=1.046, 95% CI: 1.015-1.079; OR=1.026, 95% CI: 1.005-1.047; OR=1.034, 95% CI: 1.019-1.051; OR=1.373, 95% CI: 1.088-1.733; OR=1.266, 95% CI: 1.022-1.569)were independent influencing factors of ERA. Conclusions:ERA patients exhibit elevated inflammatory markers and are more prone to anemia, liver and kidney function damage, and malnutrition.Furthermore, female ERA patients are more likely to have abnormal uric acid, alanine aminotransferase, blood lipids, and blood glucose.

Objective To assess the status of rodent infestation in commercial kitchens using data from the‘Bright Kitchen, Clean Stove' initiative. The potential use of artificial-intelligence(AI)-based surveillance systems to monitor rodent density was explored, thereby providing a scientific basis for rodent control strategies. Methods As a component of the ‘Bright Kitchen, Clean Stove' initiative, the Minhang District Market Supervision Administration in Shanghai has installed cameras in 297 kitchens. These systems incorporate an AIpowered rodent image recognition method that automatically captures and stores the first image captured in each kitchen each day when a rodent is detected. In 2023, the system collected and stored 736 screenshots of rodents. Following manual verification,720 of the images were confirmed to contain rodents. The images were analyzed by noting the time, location, and kitchen area, and the species were manually identified to assess the population density. Results Rodent activity was detected in 34 of the 297 monitored kitchens, with an overall infestation rate of 11.45%. Of the 720 confirmed images of rodents, Rattus norvegicus(brown rat)was the predominant species, present in 409(56.81 %)images. Rodents were primarily concentrated in hot food preparation spaces. The density fluctuation curve had a multimodal pattern peaking in spring and autumn. The peak of daily activity was between 22: 00 and 2: 00. There was a significant difference in the rodent detection frequency between weekends and weekdays during peak hours and during non-peak hours(χ2=7.18, P＜ 0.01). Conclusions The ‘Bright Kitchen, Clear Stove' smart monitoring system has been proven to be applicable to rodent density monitoring. To control rodents in commercial kitchens, greater efforts are required to address and identify the specific infesting conditions and the key points in the control process.

Objective:To establish the "1+3" management module of high-value consumables in Operation Room and verify its application, so as to provide new ideas for cost management of consumables in Operation Room.Methods:The Operating Room team of Shenzhen Hospital of Southern Medical University designed a "1+3" management module in 2022, where "1" referred to the management process of high-value consumables in Operation Room, and "3" referred to the precise management of consumables in Operation Room warehouse, the management of closed-loop use of Operation Room consumables and adverse event management of consumables. Surgeries using high-value consumables in the Thoracic Surgery Department, Gastrointestinal Surgery Department, and Urology Department of the hospital were selected as the research objects. The surgeries using conventional consumables from January to June 2022 were set as the control group, and the surgeries implementing the "1+3" management module from July to December 2022 were set as the observation group. The number of consumables received by the itinerant nurses before the operation and the number of high-value consumables returned after the operation were compared between the two groups. And the number of missed and error charges for high-value consumables in the two groups were counted and compared.Results:The number of consumables received before operation in the control group was higher than that in the observation group, and the difference was statistically significant ( P<0.05). The number of high-value consumables returned in the observation group was less than that in the control group, and the difference was statistically significant ( P<0.01). The proportion of missed charges for consumables in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.01), but there was no statistically significant difference in the proportion of incorrect charges between the two groups ( P>0.05) . Conclusions:The "1+3" management module for high-value consumables in Operation Room makes the process of receiving, returning, and charging high-value consumables clear, with traceable data, achieving refined management of high-value consumables in Operation Room, reducing the number of high-value consumables returned to the warehouse and reducing the proportion of missed consumables, which is conducive to effective cost control in Operation Room.