ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

ObjectiveTo investigate the effect of Yuejuwan on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice based on lipidomics， and to explore the potential pathways for improving lipid metabolism to prevent depression. MethodsSeven-week-old C57BL/6 mice were randomly divided into blank group， model group， Yuejuwan group（3.6 g·kg^-1） and fluoxetine group（10 mg·kg^-1）， and chronic unpredictable mild stress（CUMS） was used to establish the depression model. After 3 weeks of modeling， each administration group was gavaged with the corresponding drug solution according to the dose， and mice in the blank and model groups were given an equal volume of deionised water by gavage， one time/d for 2 weeks. After administration， the antidepressant effect of Yuejuwan was evaluated by neurobehavioral indices such as sucrose preference test， open field test， tail suspension test and forced swimming test. An automatic biochemical analyzer was used to measure contents of total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C）， high-density lipoprotein cholesterol（HDL-C）， aspartate aminotransferase（AST） and alanine aminotransferase（ALT） in mouse serum. Lipidomic analysis of mouse serum， prefrontal cortex and hippocampus was performed based on ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry（UPLC-LTQ-Orbitrap-MS）， and the expression of mammalian target of rapamycin（mTOR）， ribosomal protein S6 kinase（S6K）， phosphorylation（p）-mTOR， p-S6K in gastric tissues of mice was detected by Western blot. ResultsCompared with the blank group， mice in the model group exhibited significantly reduced sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly increased（P<0.01）， and serum levels of TC， TG， LDL-C， HDL-C， AST and ALT were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the Yuejuwan group showed a significant increase in the sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly reduced（P<0.01）， and the serum levels of TC， TG， LDL-C， AST and ALT were significantly decreased（P<0.05， P<0.01）. Lipidomic analysis revealed that Yuejuwan had a significant effect on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice， and The differential lipid metabolites were mainly enriched in the metabolic pathways of glycerophospholipid metabolism， sphingolipid signaling， and glycosylphosphatidylinositol-anchored protein biosynthesis， among which the glycerophospholipid metabolic pathway was the most significant. Western blot results showed that compared with the blank group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the model group were significantly increased（P<0.01）. In comparison with the model group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the Yuejuwan group were significantly decreased（P<0.01）. ConclusionThe intervention of Yuejuwan on lipid metabolism is one of the potential pathways for its antidepressant effect， which may be related to the regulation of mTOR/S6K signaling pathway upstream of lipid metabolism in the gastric tissues.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To examine the effect of a multidimensional nursing intervention based on Pender's Health Promotion Model on recovery outcomes in patients with gastrointestinal bleeding.Methods:Using convenience sampling, 200 patients with gastrointestinal bleeding who received treatment at the China-Japan Union Hospital of Jilin University from June 2023 to June 2024 were enrolled. Patients were randomly assigned by a random-number table to a control group ( n=100) receiving routine nursing or an observation group ( n=100) receiving the multidimensional nursing intervention based on Pender's Health Promotion Model in addition to routine nursing. Outcomes included bleeding control (time to melena cessation), scores on the Health-Promoting Lifestyle Profile, Generic Quality of Life Inventory, Connor-Davidson Resilience Scale 10, and the incidence of adverse events. Results:After the intervention, the time to melena cessation in the observation group was shorter than that in the control group, and the difference was statistically significant ( P<0.05). Scores on the Health-Promoting Lifestyle Profile, Generic Quality of Life Inventory, Connor-Davidson Resilience Scale 10 (all dimensions and total scores) were higher in the observation group than thoes in the control group, and the differences were statistically significant ( P<0.05). The incidence of adverse events was 3.00% (3/100) in the observation group versus 11.00% (11/100) in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:In patients with gastrointestinal bleeding, a multidimensional nursing intervention based on Pender's Health Promotion Model optimizes bleeding control, strengthens psychological resilience, improves health status and quality of life, and reduces adverse events. This approach merits wider clinical adoption.

Objective:To examine the effect of a multidimensional nursing intervention based on Pender's Health Promotion Model on recovery outcomes in patients with gastrointestinal bleeding.Methods:Using convenience sampling, 200 patients with gastrointestinal bleeding who received treatment at the China-Japan Union Hospital of Jilin University from June 2023 to June 2024 were enrolled. Patients were randomly assigned by a random-number table to a control group ( n=100) receiving routine nursing or an observation group ( n=100) receiving the multidimensional nursing intervention based on Pender's Health Promotion Model in addition to routine nursing. Outcomes included bleeding control (time to melena cessation), scores on the Health-Promoting Lifestyle Profile, Generic Quality of Life Inventory, Connor-Davidson Resilience Scale 10, and the incidence of adverse events. Results:After the intervention, the time to melena cessation in the observation group was shorter than that in the control group, and the difference was statistically significant ( P<0.05). Scores on the Health-Promoting Lifestyle Profile, Generic Quality of Life Inventory, Connor-Davidson Resilience Scale 10 (all dimensions and total scores) were higher in the observation group than thoes in the control group, and the differences were statistically significant ( P<0.05). The incidence of adverse events was 3.00% (3/100) in the observation group versus 11.00% (11/100) in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:In patients with gastrointestinal bleeding, a multidimensional nursing intervention based on Pender's Health Promotion Model optimizes bleeding control, strengthens psychological resilience, improves health status and quality of life, and reduces adverse events. This approach merits wider clinical adoption.

Objective To investigate the effect of long non-coding RNA(lncRNA)potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1(KCNQ1OT1)on oxidative glucose deprivation/reoxygenation(OGD/R)-induced microglia injury through regulating the miR-145-5p/Rho-associated coiled-coil forming protein kinase 1(ROCK1)axis.Methods Microglia N9 were divided into the control group(normal culture),the OGD/R group(OGD/R-induced injury),the sh-NC group(transfected with sh-NC after OGD/R-induced injury),the sh-KCNQ1OT1 group(transfected with sh-KCNQ1OT1 after OGD/R-induced injury),the sh-KCNQ1OT1+inhibitor NC group(co-transfected with sh-KCNQ1OT1 and inhibitor NC after OGD/R-induced injury),and the sh-KCNQ1OT1+miR-145-5p inhibitor group(co-transfected with sh-KCNQ1OT1 and miR-145-5p inhibitor after OGD/R-induced injury).RT-qPCR was applied to detect the expression of lncRNA KCNQ1OT1,miR-145-5p,and ROCK1 mRNA in cells.The expression of ROCK1 protein was detected by Western blot.CCK-8 was applied to detect the cell proliferation.Flow cytometry was applied to detect cell apoptosis.ELISA was applied to detect the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in cells.The action sites of miR-145-5p with lncRNA KCNQ1OT1 and ROCK1 were predicted by bioinformatics website,and their targeting relationships were verified by dual-luciferase reporter assay.Results Compared with the control group,the expression of lncRNA KCNQ1OT1,the expression of ROCK1 mRNA and protein,the apoptosis rate,and the levels of IL-6,TNF-α,and IL-1β in cells were all increased,and the level of miR-145-5p and cell survival rate were all decreased in the OGD/R group(P<0.05).Compared with the OGD/R group and the sh-NC group,the expression of lncRNA KCNQ1OT1,the expression of ROCK1 mRNA and protein,the apoptosis rate,and the levels of IL-6,TNF-α,and IL-1β in cells were all decreased,and the level of miR-145-5p and cell survival rate were all increased in the sh-KCNQ1OT1 group,with significant differences(P<0.05).Compared with the sh-KCNQ1OT1+inhibitor NC group,the expression of ROCK1 mRNA and protein,the apoptosis rate,and the levels of IL-6,TNF-α,and IL-1β in cells were all increased,and the expression of miR-145-5p and cell survival rate were all decreased in the sh-KCNQ1OT1+miR-145-5p inhibitor group,with significant differences(P<0.05).Bioinformatics website showed that miR-145-5p had targeted action sites with lncRNA KCNQ1OT1 and ROCK1,and dual-luciferase reporter assay confirmed that miR-145-5p had targeting relationships with lncRNA KCNQ1OT1 and ROCK1(P<0.05).Conclusion Silencing lncRNA KCNQ1OT1 can alleviate OGD/R-induced microglia injury via upregulating the expression of miR-145-5p and targeting the down-regulation of ROCK1 expression.