Pulmonary hypertension （PH） is a life-threatening condition characterized by a progressive elevation in pulmonary vascular pressure， ultimately leading to right ventricular dysfunction and failure. The core pathological features of PH include abnormal contraction of small pulmonary arteries and vascular remodeling. In recent years， endoplasmic reticulum stress （ERS）， a critical adaptive response of cells to internal and external stressors， has been shown to play a key role in the development and progression of PH. Through the activation of major signaling pathways such as protein kinase R-like endoplasmic reticulum kinase （PERK）， inositol-requiring enzyme 1α （IRE1α）， and activating transcription factor 6 （ATF6）， ERS is directly involved in regulating aberrant cellular behaviors and vascular remodeling in PH. This review systematically discusses the specific role of ERS in the pathogenesis of PH and evaluates its potential as a therapeutic target， aiming to provide a theoretical foundation for novel clinical interventions in PH.

ObjectiveNonalcoholic fatty liver disease （NAFLD） is a metabolic stress liver injury. Ferroptosis is involved in the occurrence and development of NAFLD. Exploring the efficacy and mechanism of schisandrin B in treating NAFLD facilitates the development of strategies for the prevention and treatment of NAFLD. MethodsThe molecular structure of schisandrin B was obtained by searching against PubChem， and the related targets were predicted by SwissTargetPrediction. The active ingredients and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the high-throughput experiment- and reference-guide database of traditional Chinese medicine （HERB）. GeneCards and FerrDb were searched for the targets of NAFLD and ferroptosis. The common targets were taken as the core targets， and the protein-protein interaction network of the core targets was established. DAVID was used for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses. Finally， molecular docking was performed between schisandrin B and core targets， and the binding energy was calculated. C57BL/6 mice were fed with a methionine and choline-deficiency （MCD） diet for the modeling of NAFLD. Mice were randomized into normal， model， positive drug （essentiale）， and low- and high-dose schisandrin B groups. The body mass and liver index of mice were measured after drug administration. The levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum and those of total cholesterol （TC）， triglyceride （TG）， malondialdehyde （MDA）， glutathione （GSH）， and Fe²⁺ in the liver homogenate were measured by biochemical assay kits. The pathological changes of the liver tissue were observed by hematoxylin-eosin （HE） and red oil O staining. Enzyme-linked immunosorbent assay was employed to determine the levels of interleukin （IL）-6， IL-1β， tumor necrosis factor （TNF）-α， and 4-hydroxynonenal （4-HNE） in the serum. Western blotting and real-time PCR were employed to determine the protein and mRNA levels， respectively， of solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， glutathione peroxidase 4 （GPX4）， transferrin， and ferritin heavy chain （FTH） in the liver tissue. ResultsA total of 2 370， 2 547， and 1 451 targets of schisandrin B， NAFLD， and ferroptosis were obtained， in which 90 common targets were shared by the three. Enrichment analyses predicted 505 GO terms and 92 KEGG pathways. Molecular docking suggested that schizandrin B had strong binding affinity with the key targets of ferropstosis （SLC7A11 and SLC3A2）. Animal experiments showed that schizandrin B significantly decreased the liver index， lowered the levels of ALT， AST， TC， TG， IL-6， IL-1β， and TNF-α， alleviated hepatocyte ballooning and inflammatory cell infiltration， and reduced lipid accumulation in the liver of NAFLD mice. In addition， schisandrin B significantly lowered the levels of MDA， 4-HNE， and Fe²⁺， elevated the level of GSH， up-regulated the protein and mRNA levels of SLC7A11， SLC3A2， and GPX4， and down-regulated the protein and mRNA levels of transferrin in the liver tissue. ConclusionSchisandrin B can alleviate NAFLD by inhibiting ferroptosis in hepatocytes.

Ionizing radiation (IR) is a genotoxic agent that can play an important role in the occurrence and development of various diseases by inducing epigenetic changes. Studies have shown that the basic mechanisms of IR-induced epigenetic changes include abnormal DNA methylation, increased oxidative stress levels, changes in histone modifications, and regulation by microRNAs. These can lead to health hazards such as malignant tumors, genetic effects, nervous system damage, circulatory system diseases, and radiation-induced cataracts. This article collected relevant literatures regarding epigenetic changes induced by IR from 2005 to 2024, and reviewed the basic mechanisms of IR-induced epigenetic changes and the associated disease risks, providing the reference for radiation protection in occupational exposure and radiotherapy.

Objective:To explore the correlation between the oxygenation index and the monitored parameters of lung injury view in ventilator,so as to provide a basis for monitoring the change of oxygenation index by the parameters of lung injury view.Methods:A total of 28 patients who received mechanical ventilation treatment and admitted to respiratory department of the First Affiliated Hospital with Nanjing Medical University from May 14 to September 30,2024 were selected.The monitored parameters of lung injury views of them during mechanical ventilation treatment with invasive ventilators were collected,including platform pressure(Pplat),driving pressure(ΔP),mechanical energy(Emech),ratio of tidal volume to ideal body weight(TVe/IBW),etc..Then,the data of oxygenation index were obtained.Finally,135 valid data were screened out.The 84 pieces of data with oxygenation index≤300mmHg were included in low oxygen group,and 51 data with oxygenation index>300mmHg were included in normal group.The correlations between oxygenation index and Pplat,ΔP,Emech,TVe/IBW were conducted by pairwise analysis.Results:In the low oxygen group,the oxygenation index was[(196.302±74.522)mmHg]significantly negative correlation with Emech[(12.686±5.401)J/min](ρ=-0.425,P<0.05),but not was significant correlation with Pplat,ΔP,and TVe/IBW(P>0.05).In the normal group,there were not significant correlations between the oxygenation index and Pplat,ΔP,Emech and TVe/IBW(P>0.05).There was a significant negative correlation between Emech and rank of oxygenation index(β=-0.389,P<0.05)in the low oxygen group.Conclusion:The visualization function of the Emech of the monitored parameters in lung injury view of ventilator can provide help for monitoring the changes of oxygenation index of patients in the low oxygen group,and can improve the oxygenation of patients by optimizing mechanical energy.However,it is necessary to balance the contradiction between ventilation intensity and protection for lung.

AIM:To observe the effects of Huangqi-Danggui mixture(HQDG)on the pyroptosis of brain tis-sues in rats with middle cerebral artery occlusion/reperfusion(MCAO/R),and to explore the mechanism of neuroprotec-tion provided by HQDG.METHODS:Sixty-four SD rats were randomly divided into 4 groups:sham group,model group,HQDG group,and Xuesaitong(XST)group.The infarct volume of brain tissues was observed by 2,3,5-triphenyl-tetrazolium chloride staining,while hematoxylin-eosin staining was used to observe the pathological changes of brain tis-sues.Immunofluorescence was employed to assess the expression of nucleotide-binding oligomerization domain-like recep-tor protein 3(NLRP3),cleaved caspase-1 and gasdermin D(GSDMD)in the ischemic penumbra of brain tissues.The se-rum levels of interleukin-1β(IL-1β)and IL-18 were measured using ELISA.Western blot was used to detect NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),IL-1β and IL-18 in brain tissues.RESULTS:Compared with sham group,the neurological deficit scores of the rats in model group were significantly increased(P<0.01),while those in HQDG and XST groups were significantly reduced compared with model group(P<0.01).The cerebral infarct volume ratio was significantly reduced in HQDG and XST groups compared with model group(P<0.01).The pathological damage of brain tissue in HQDG and XST groups was significantly reduced compared with model group.The positive rates of NLRP3,cleaved caspase-1 and GSDMD in the ischemic penumbra of brain tissues were significantly decreased in HQDG group compared with model group(P<0.01).The expression of pyrop-tosis-related proteins,NLRP3,cleaved caspase-1 and ASC,in the ischemic penumbra of brain tissues was significantly el-evated in model group compared with sham group(P<0.01),and significantly decreased in HQDG group compared with model group(P<0.01).The serum levels of IL-1β and IL-18 were significantly increased in model group compared with sham group(P<0.01),and significantly reduced in HQDG group compared with model group(P<0.01).CONCLU-SION:The HQDG effectively attenuates brain tissue injury in rats with MCAO/R,and its mechanism may be related to the inhibition of neural cell pyroptosis.

Objective To explore the mechanism of 1,25-dihydroxy vitamin D3[1,25(OH)2D3]in renal interstitial fibrosis mediated by nuclear factor κB(NF-κB)and inflammatory cytokines.Methods Taking the renal interstitial fibrosis model induced by transforming growth factor-β1(TGF-β1)as the research object,they were divided into blank group(HK-2 cells+complete culture medium),model group(5ng/ml TGF-β1 stimulated HK-2 cells for 48 hours),intervention group A[with 10-7mol/L 1,25(OH)2D3 intervention for 24 hours on the basis of model group],intervention group B[with 10-7mol/L 1,25(OH)2D3 intervention for 48 hours on the basis of model group]and intervention group C[with 10-7mol/L 1,25(OH)2D3 intervention for 72 hours on the basis of model group].The cell morphology,activity,protein expression and inflammatory factor levels of each group were observed and compared.Results The cell viability of model group was significantly lower than that of blank group(P＜0.05),the cell viability of intervention groups A,B and C was significantly higher than that of model group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and smooth muscle actin α(α-SMA),as well as the levels of interleukin-6(IL-6)and tumor necrosis factor α(TNF-α)in model group were significantly higher than those in blank group,while the protein expression of E-cadherin was significantly lower than that in blank group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and α-SMA,as well as the levels of IL-6 and TNF-α in intervention groups A,B and C were significantly lower than those in model group,while protein expression of E-cadherin was significantly higher than that in model group(P＜0.05).Among them,the change in intervention group A was the most significant.Conclusion 1,25(OH)2D3 can alleviate renal interstitial fibrosis by regulating the NF-κB signaling pathway and inflammatory cytokines,and 24 hours may be the optimal intervention time window.

Objective To investigate the inhibitory effect of running combined with chitosan on high-fat diet(HFD)induced obesity in rats through the expression of fatty acid transporter 4(FATP4)and Toll like receptor 4(TLR4)and its mechanism.Methods 50 male Wistar rats were randomly divided into normal control(NC)group,HFD group,chitosan(Chi)group,running exercise(Run)and chitosan+running exercise(Chi+Run)group,with 10 rats in each group.The levels of serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),very low density lipoprotein cholesterol(VLDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected.ELISA was used to detect serum TNF-α,IL-6,APN,Ghrelin,Leptin(LP),and Ins levels.Western blot was used to test the expression of FATP4 and TLR4 proteins in liver and adipose tissue,and HE staining was used to evaluate liver and adipose tissue pathology.Results Compared with the HFD group,the Chi,Run,and Chi+Run groups showed an increase in HDL-C,serum APN,and Ghrelin(P<0.05),as well as an decreased in body weight,fat mass,obesity index,TC,TG,LDL-C,VLDL-C,ALT,AST,TNF-α,IL-6,LP,Ins,FATP4 protein expression,TLR4 protein expression,adipocyte size and quantity in liver and adipose tissue(P<0.05).The HDL-C was higher in Chi+Run group than in Chi and Run groups(P<0.05),and the final weight,LDL-C,TG,AST,IL-6,the expression of FATP4 protein,TLR4 protein,and adipocyte size in the liver and adipose tissue were lower in Chi+Run group than in Chi and Run groups(P<0.05).Conclusions The inhibitory effect of running combined with Chi on HFD induced obesity was superior to that of running or Chi alone,and its mechanism may be related to the downregulation of FATP4 and TLR4.

The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

The accurate and timely detection of biochemical coagulation indicators is pivotal in pulmonary and critical care medicine. Despite their reliability, traditional laboratories often lag in terms of rapid diagnosis. Point-of-care testing (POCT) has emerged as a promising alternative, which is awaiting rigorous validation. We assessed 226 samples from patients at the First Affiliated Hospital of Guangzhou Medical University using a Beckman Coulter AU5821 and a PUSHKANG POCT Biochemistry Analyzer MS100. Furthermore, 350 samples were evaluated with a Stago coagulation analyzer STAR MAX and a PUSHKANG POCT Coagulation Analyzer MC100. Metrics included thirteen biochemical indexes, such as albumin, and five coagulation indices, such as prothrombin time. Comparisons were drawn against the PUSHKANG POCT analyzer. Bland-Altman plots (MS100: 0.8206‒0.9995; MC100: 0.8318‒0.9911) evinced significant consistency between methodologies. Spearman correlation pinpointed a potent linear association between conventional devices and the PUSHKANG POCT analyzer, further underscored by a robust correlation coefficient (MS100: 0.713‒0.949; MC100: 0.593‒0.950). The PUSHKANG POCT was validated as a dependable tool for serum and whole blood biochemical and coagulation diagnostics. This emphasizes its prospective clinical efficacy, offering clinicians a swift diagnostic tool and heralding a new era of enhanced patient care outcomes.
Humans ; Point-of-Care Testing ; Critical Care ; Blood Coagulation Tests/methods* ; Male ; Blood Coagulation ; Female ; Middle Aged ; Reproducibility of Results ; Prothrombin Time ; Aged ; Adult ; Point-of-Care Systems

Objective: To investigate the effects of “Three Methods and Three Acupoints” (TMTP) Tuina therapy on spinal microcirculation in sciatic nerve injury (SNI). Methods: Thirty-six Sprague–Dawley rats were randomly assigned to four groups: normal, sham operation, model, and TMTP Tuina. Successful model induction was confirmed by observable hind limb lameness. After 20 sessions, hind limb grip strength and motor nerve conduction velocity (MNCV) were measured at baseline and following the 10th and 20th intervention. CD31 and α-SMA in the ventral horn of SNI model rats were detected using immunofluorescence. Motor neurons in the ventral horn were detected by Nissl staining. PTEN levels in the ventral horn were measured by ELISA, and PI3K, Akt, BDNF, VEGF, and HIF-1α expression was determined by RT-PCR. Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt, p-Akt, BDNF, and VEGF. Results: Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group (both P < .001). Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group, with increased expressions of α-SMA (P = .002) and CD31 (P = .006). Western blot analysis indicated increased expression of VEGF (P = .005), p-Akt (P < .001), and BDNF (P = .008) in the ventral horn following Tuina treatment. RT-PCR analysis revealed increased expression of PI3K, Akt, BDNF, VEGF and HIF-1α (all P < .05). In contrast, expression of PTEN decreased compared to the model group (P < .001). Conclusion TMTP Tuina therapy may restore motor function in rats, enhance ventral horn motor neuron morphology, and promote angiogenesis and vascular smooth muscle proliferation. The mechanism may involve the activation of the PI3K/Akt signaling pathway.