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.

This article summarized the current status and challenges of manipulation therapy for musculoskeletal pain and its placebo effect in clinical trials, analyzing the impact of the placebo effect on the evaluation of therapeutic efficacy. The efficacy of different manual manipulation techniques remains uncertain, and the degree of blinding and patient expectations play a crucial role in efficacy assessment. The article suggested improving trial design through standardized placebo intervention design, comprehensive investigation of patient expectations and psychological states, rigorous training of practitioners, and optimized diagnostic and treatment scenarios and doctor-patient relationship, to ensure consistency between intervention and placebo groups. Specific measures include the application of the DITTO (Deconstruct, Identify, Take out, Think, Optimize) framework, the use of standardized questionnaire tools, and multi-center, large-sample randomized controlled trials to enhance the external validity and statistical power of research results, thereby providing more scientifically reliable evidence for clinical practice.

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 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.

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.

This article reports three cases of refractory ulcerative colitis in children treated with vedolizumab. Combined with domestic and foreign literature, the effectiveness and safety of the drug for children are discussed to provide a reference for the subsequent exploration of individualized treatment.

Inflammatory bowel disease (IBD), a chronic recurrent inflammatory bowel disease, is associated with depression and anxiety. Intestinal inflammation increases susceptibility to psychiatric disorders through a multidimensional network of immune-inflammatory, neuroendocrine, intestinal flora, and intestinal barrier abnormalities. Conversely, psychiatric stress exacerbates the pathology of IBD through immune regulation, intestinal barrier disruption, and microenvironmental alterations. Therefore, it is important to explore the mechanisms of comorbidity between IBD and depression and anxiety to optimise clinical management. This article reviews the comorbid mechanisms of IBD and depression and anxiety from the perspectives of immune-inflammatory axis, intestinal flora-metabolic pathway, intestinal barrier dysfunction, and neuroendocrine regulation in the context of rodent models, and explore potential intervention strategies, with the aim of providing new ideas and targets for therapeutic and transformation research in this field.

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 analyze the clinical distribution characteristics and drug resistance of Enterobacter cloa-cae in Gansu Province from 2019 to 2023,providing reference for the prevention and control of E.cloacae infec-tions in this region.METHODS Data on the distribution and drug resistance of E.cloacae from hospitals in mem-ber units of the Gansu Antimicrobial Surveillance Network between 2019 and 2023 were collected.In vitro drug susceptibility testing was performed by the Kirby-Bauer disk diffusion(K-B)method,minimum inhibitory con-centration method,and fully automated instrumentation,followed by analysis of the susceptibility results.RESULTS From 2019 to 2023,a total of 402 490 bacterial strains were isolated and cultured in Gansu Province,including 17 417 strains of E.cloacae,with a detection rate of 4.33％.The bacteria were primarily iso-lated from sputum specimens(62.81％),followed by urine(7.37％)and wound pus specimens(6.07％).The de-partmental distribution was dominated by internal medicine(44.96％)and surgery(28.50％).The highest detec-tion rate was observed in the adult group(15-65 years,45.79％).E.cloacae exhibited varying degrees of resist-ance to over 20 antibacterial drugs,but the overall drug resistance rate showed a declining trend(P＜0.05).The highest drug resistance rate was observed for cefazolin(96.40％-98.38％),while the lowest was for tigecycline(0.44％—2.92％).Carbapenem-resistant E.cloacae demonstrated an increasing trend in drug resistance rates,with imipenem resistance ranging from 2.79％to 3.71％(P=0.044)and meropenem resistance ranging from 1.29％to 3.41％(P＜0.05).CONCLUSIONS The isolation rate of E.cloacae in Gansu Province remains stable,with a declining trend in drug resistance to multiple antibacterial drugs.However,the increasing drug resistance to carbapenems warrants attention.