ObjectiveTo investigate the mechanism of action of remifentanil （RMZL） in alleviating lung ischemia-reperfusion injury （LIRI） in rats by inhibiting pyroptosis through modulating hypoxia inducible factor-1α （HIF-1α）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. MethodsRats were stochastically assigned into Control group， LIRI group， RMZL low-dose group， RMZL medium-dose group， RMZL high-dose group， and RMZL high-dose+HIF-1α activator dimethyloxallyl glycine （DMOG） group， with 18 rats in each group. Rats in Control group only had their left pulmonary hilum free and did not undergo ischemia-reperfusion treatment. Except for the Control group， LIRI models were constructed in all other groups. Rats in LIRI group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before constructing LIRI model； rats in Control group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before freeing left pulmonary hilum； rats in other groups were intraperitoneally injected with corresponding dose of drug 15 minutes before constructing LIRI model. The wet/dry weight ratio of lungs was calculated. HE staining was used to study lung tissue pathology. Immunofluorescence staining was used to detect the relative fluorescence intensity of gasdermin D （GSDMD） and NLRP3 double positive cells in lung tissue. ELISA was used to detect interleukin-1β and IL-18 in lung tissue. Western blot was used to detect HIF-1α， NLRP3， cysteine-aspartic protease-1 （Cleaved caspase-1）， and gasdermin D-N （GSDMD-N） proteins in lung tissue. ResultsCompared to the Control group， the LIRI group showed disordered alveolar structure， thickened alveolar septa， and abundant inflammatory cell infiltration in rats. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins increased （P0.05）. For the LIRI group， rats in the RMZL low， medium， and high-dose groups displayed attenuated alveolar septal thickening and reduced inflammatory cell infiltration. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins declined， and the RMZL high-dose group showed the most prominent trend （P0.05）. Compared with the RMZL high-dose group， rats in the RMZL high-dose+DMOG group exhibited thickened alveolar septa and more inflammatory cell infiltration， along with increased lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， levels of IL-1β and IL-18， and protein expression of HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N （P0.05）. ConclusionRMZL may inhibit pyroptosis in LIRI rats by suppressing HIF-1α/NLRP3 pathway.

ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

In the context of continuously deepening medical and health system reforms and comprehensively promoting the "Healthy China" strategy, Henan Provincial People's Hospital has established a regional collaborative and vertically integrated critical care service structure and network. This initiative aims to enhance information empowerment, strengthen regional collaboration, improve the insufficient primary medical services, and ensure timely and effective treatment for critically ill patients. By establishing a comprehensive dispatch service platform for regional collaborative critical care, building a "top-down" remote medical collaboration network, and forming a cross-regional specialty alliance for critical care, the hospital has improved the efficiency of medical services and enhanced regional capabilities for treating critically ill patients. Simultaneously, for critically serious patients and those with complex diseases at primary medical institutions, a one-stop consultation and referral service has been implemented. This service adopts a "three specialists" approach and a multidisciplinary consultation mechanism within the hospital, constructs a multi-dimensional critical care transfer mode integrating air, ground, and the internet, creates a regional collaborative rescue mode, and implements full-cycle treatment for critically serious patients. The comprehensive, flexible, and efficient service pathway for regional collaborative critical care established by this system ensures timely and safe treatment for critically ill patients, promotes the distribution of high-quality medical resources, and effectively addresses issues such as uneven distribution of high-quality medical resources and varying levels of critical care capabilities. It has facilitated the formation of a new tiered diagnosis and treatment order characterized by "first diagnosis at the primary level, two-way referral, separate treatment for acute and chronic diseases, and vertical integration". This approach has enhanced the diagnostic and comprehensive service capabilities of primary medical institutions. Currently, by strengthening information empowerment and sharing, creating a full-process critical care diagnosis and treatment model, providing medical assistance and cultivating primary-level critical care talent, and promoting appropriate technologies, the hospital has gradually overcome challenges such as barriers to information exchange and sharing between hospitals, overloaded critical care teams, high pressure on patient reception and transfer, and limited critical care capabilities at primary medical institutions. This article summarizes the construction and practical application of this regionally coordinated critical care system, aiming to provide a reference for the management of critical care treatment.
Humans ; China ; Critical Care/organization & administration* ; Delivery of Health Care/organization & administration*

Natural products (NPs) have long held a significant position in various fields such as medicine, food, agriculture, and materials. The chemical space covered by NPs is extensive but often underexplored. Therefore, high-throughput and efficient methodologies for the annotation and discovery of NPs are desired to address the complexity and diversity of NP-based systems. Mass spectrometry (MS) has emerged as a powerful platform for the annotation and discovery of NPs. MS databases provide vital support for the structural characterization of NPs by integrating extensive mass spectral data and sample information. Additionally, the released annotation methodologies, based on a variety of informatics tools, continuously improve the ability to annotate the structure and properties of compounds. This review examines the current mainstream databases and annotation methodologies, focusing on their advantages and limitations. Prospects for future technological advancements are then discussed in terms of novel applications and research objectives. Through a systematic overview, this review aims to provide valuable insights and a reference for MS-based NPs annotation, thereby promoting the discovery of novel natural entities.
Biological Products/chemistry* ; Mass Spectrometry/methods* ; Databases, Factual ; Drug Discovery/methods* ; Humans

ObjectiveTo analyze the epidemiological characteristics of clustered vomiting and diarrhea outbreaks in Minhang District of Shanghai, to identify the influencing factors of outbreak scale and duration of epidemic, and to provide scientific evidence for further strengthening surveillance early-warning efforts in key settings and for optimizing prevention and control measures. MethodsThe data for describing epidemiological characteristics of clustered vomitting and diarrhea outbreaks in Minhang District from 2018 to 2023 were collected, multivariable logistic regression models were applied to analyze the influencing factors for epidemic scale,and Spearman rank correlation analyses were applied to analyze the factors duration. ResultsA total of 136 clustered vomiting and diarrhea outbreaks were reported in Minhang District from 2018 to 2023, all occurring in school settings, with an overall attack rate of 0.90%. The outbreaks exhibited distinct seasonality, predominantly occurring from October to December (43.38%) and March to May (32.35%). The primary settings were preschools (45.59%) and elementary schools (44.12%), with students accounted for the majority of cases (99.48%). The predominant clinical manifestation was vomiting (90.44%), with person-to-person contact being the primary transmission route (98.53%). Norovirus genogroup Ⅱ was identified as the main pathogen (71.32%). Standardized terminal disinfection of outbreak sites (OR=0.39, 95%CI=0.20‒0.74) and effective isolation of affected classes (OR=0.23, 95%CI=0.09‒0.57) were significant protective factors for reducing outbreak scale. Both response time (r=0.64, P<0.001) and the number of case generations (r=0.71, P<0.001) showed positive correlations with outbreak duration. ConclusionSchools are the key settings for the prevention and control of clustered vomiting and diarrhea outbreaks in Minhang District, with peak occurring in autumn and spring. Early detection, timely reporting, and prompt response to outbreaks are crucial. Strengthening school-based surveillance systems and standardizing outbreak management protocols are of particular importance.

The study was a prospective observational study. A total of 24 patients who underwent maintenance hemodialysis (MHD) at Haidian Hospital in Beijing from May 2024 to June 2024 were included as the study subjects. The safety and efficacy of a new single-needle dialysis in MHD patients were evaluated. The reasons for using single-needle dialysis included waiting for the maturity of internal fistula(7 cases, 29.17%), autogenous arteriovenous fistula thrombosis occurred (6 cases, 25.00%), puncture difficulty occurred (7 cases, 29.17%), and pain sensitivity or elderly (4 cases, 16.67%). The results showed that the average blood flow was (155.65±5.90) ml/min, total blood volume was (35.92±2.65) L during single-needle dialysis. One patient had slight puncture leakage, and the puncture success rate was 95.83%. Relevant indicators of dialysis adequacy showed that the average urea clearance (Kt/V) was 0.90±0.42, urea reduction ratio was 58.31%±7.93%, and online real-time Kt/V monitoring average value was 0.98±0.55. The results suggest that the application of the new improved single-needle dialysis mode in MHD patients is safe and effective.

Objective:To assess the effect of joint exposure to multiple air pollutants on sleep structure in patients with stable chronic obstructive pulmonary disease (COPD), identify key air pollutants, and analyze potential influencing factors.Methods:In this panel study, 92 stable COPD patients were recruited. From March 2021 to September 2023 in Beijing, all participants completed 254 nights of sleep monitoring. The total sleep duration, light sleep duration, deep sleep duration and rapid eye movement sleep duration and their respective proportions in total sleep duration were recorded. The exposure levels of fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), ozone (O 3), sulfur dioxide (SO 2), and carbon monoxide (CO) were estimated based on the infiltration factor method and time-activity logs of participants. To assess the lag effect of air pollutants, moving average concentrations of air pollutants from 0-1 day to 0-3 months were calculated. The linear mixed-effect model and Bayesian kernel machine regression (BKMR) model were used to assess the single and joint effects of air pollutants on sleep structure parameters in COPD patients, respectively. Results:All six types of air pollutants were associated with changes in sleep structure, manifesting as an increase in total sleep duration and light sleep proportion and a reduction in deep sleep proportion. The effects of O 3 were strongest at lag 0-6 days, while other air pollutants were at lag 0-3 months. Joint exposure to multiple air pollutants exerted significant joint effects on sleep structure, and NO 2 was identified as the dominant pollutant. NO 2 had a posterior inclusion probability (PIP) greater than 0.5 for light sleep proportion (PIP=0.691) and deep sleep proportion (PIP=0.957). With an interquartile range (IQR) increase of 8.6 μg/m 3 in NO 2 at lag 0-3 months, the light sleep proportion increased by 10.5% (95% CI: 2.2%-19.4%), and the deep sleep proportion decreased by 19.5% (95% CI:-30.6%- -6.8%). Conclusion:Joint exposure to air pollutants is associated with changes in sleep structure in stable COPD patients, and NO 2 may be a key pollutant.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective To investigate the relationship between traditional Chinese medicine(TCM)syndromes and biological indicators of neutrophil-to-lymphocyte ratio(NLR),systemic immune-inflammatory index(SII),systemic inflammation response index(SIRI),and aggregate index of systemic inflammation(AISI)in obese type 2 diabetes mellitus(T2DM)patients complicated with Helicobacter pylori(Hp)infection.Methods From January 2023 to July 2024,an investigation was carried out in 200 cases of obese T2DM patients complicated with Hp infection,20 cases of obese T2DM patients without Hp infection(Hp-negative),and 20 obese individuals without Hp infection(Hp-negative)who met the inclusion criteria and were treated at Linhai Hospital of Traditional Chinese Medicine.The relationships between different groups of obese individuals and biological indicators of NLR,SII,SIRI,and AISI were observed.And the correlation of TCM syndromes and the presence of chronic complications with biological indicators of NLR,SII,SIRI,and AISI in obese T2DM patients complicated with Hp infection was also explored.Results(1)The levels of NLR,SII,SIRI,and AISI in obese T2DM patients complicated with Hp infection were higher than those in obese T2DM patients(Hp-negative)and obese individuals(Hp-negative)(P＜0.05).(2)Among the 200 cases of obese T2DM patients with Hp infection,the distribution of TCM syndromes in descending order was as follows:phlegm-turbidity blocking the middle energizer syndrome(29.50%)＞phlegm blended with heat syndrome(21.50%)＞qi stagnation and blood stasis syndrome(20.00%)＞liver depression and spleen deficiency syndrome(19.00%)＞qi and yin deficiency syndrome(10.00%).(3)The levels of NLR,SII,SIRI,and AISI varied in obese T2DM patients with Hp infection of various TCM syndrome types,and they were in descending order in the following types:phlegm blended with heat syndrome＞qi stagnation and blood stasis syndrome＞liver depression and spleen deficiency syndrome＞phlegm-turbidity blocking the middle energizer syndrome＞qi and yin deficiency syndrome(P＜0.05).(4)Logistic regression analysis showed that NLR,SII,SIRI,and AISI were the risk factors of chronic complications in obese T2DM patients complicated with Hp infection,and all were positively correlated with the chronic complications(P＜0.05 or P＜0.01).Conclusion NLR,SII,SIRI,and AISI are correlated with the severity of obese T2DM complicated with Hp infection,which may serve as potential biological indicators for TCM syndrome differentiation and identification of chronic complications in obese T2DM patients complicated with Hp infection.

[Objective]To investigate the correlation between traditional Chinese Medicine(TCM)syndrome types in patients with diabetic nephropathy(DN)and leukocyte lymphocyte ratio(WLR),platelet/lymphocyte ratio(PLR),monocyte lymphocyte ratio(MLR).[Methods]A total of 227 patients with DN and AS were included in this study to analyze the changes of WLR,PLR,MLR,carotid intima-medial thickness(IMT)and the levels of WLR,PLR and MLR under different TCM syndrome types.Logistic analysis and receiver operating characteristic(ROC)curves were used to evaluate the application value of WLR,PLR and MLR in predicting the severity and prognosis of DN complicated with AS.[Results]Among the TCM syndrome types in patients with DN and AS,Qi and Yin deficiency syndrome accounted for the highest proportion,followed by spleen and kidney Yang deficiency syndrome,Yin and Yang deficiency syndrome,and turbidity and stasis obstruction syndrome.The levels of WLR,PLR,and MLR in patients with DN and AS from high to low were turbidity and stasis obstruction syndrome,Yin and Yang deficiency syndrome,spleen and kidney Yang deficiency syndrome,and Qi and Yin deficiency syndrome.WLR,PLR,MLR were positively correlated with IMT(P<0.05).Logistic analysis showed that the levels of WLR,PLR and MLR were correlated with the severity of DN and AS.ROC curve analysis indicated WLR,PLR,MLR had high value in evaluating the prognosis of DN combined with AS(P<0.05).[Conclusion]WLR,PLR and MLR are expected to be potential biological indicators for microscopic syndrome differentiation and prognosis evaluation of DN combined with AS in TCM.