Objective: To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis (KOA) model. Methods: Rabbits (n = 18) were randomly divided into control, KOA, and KOA + acupotomy (Apo) groups (n = 6). The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks. After modeling, the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis, vastus lateralis, rectus femoris, biceps femoris, and anserine bursa tendons around the knee. The behavior of all animals was recorded, rectus femoris tissue was obtained, and histomorphological changes were observed using Masson staining and transmission electron microscopy. The expression of transforming growth factor-β1 (TGF-β1), Smad 3, Smad 7, fibrillar collagen types I (Col-I) and III (Col-III) was detected using Western blot and real-time polymerase chain reaction (RT-PCR). Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris, compared with the KOA group (P = .034). Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA, thus preventing skeletal muscle fibrosis. Western blot and RT-PCR analysis revealed that in the Apo group, Col-I, and Col-III protein levels were significantly lower than those in the KOA group (both P < .01), same as Col-I and Col-III mRNA levels (P = .0031; P = .0046). Compared with the KOA group, the protein levels of TGF-β1 and Smad 3 were significantly reduced (both P < .01), as were the mRNA levels of TGF-β1 and Smad 3 (P = .0007; P = .0011). Conversely, the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group (P < .01; P = .0271). Conclusion Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.

From September 26 to 28,2024,the 11th Korean International Gastric Cancer Week(KINGCA WEEK 2024),a prestigious academic conference in the field of gastric cancer,was held in Seoul.Organized by the Korean Gastric Cancer Association,the conference featured one main venue,18 sub-venues,and 16 thematic symposiums,including 100 invited presentations and four keynote speeches,attracting 788 experts and scholars from around the world.Additionally,the conference set 16 themes and received 425 submissions from 24 countries,including Republic of Korea,China,Japan,and the United States.After a review process,365 submissions were accepted,which included eight plenary oral presentations,78 oral reports,and 279 poster presentations.The conference covered many hot topics in gastric cancer diagnosis and treatment,with a particular focus on surgical-related areas such as treatment strategies for metastatic gastric cancer,an international consensus meeting on the conversion therapy for stage Ⅳgastric cancer,future research directions of the Korean Laparoendoscopic Gastrointestinal Surgery Study Group,the development of new surgical instruments and equipment,and key issues in lymph node dissection,resection,and reconstruction during minimally invasive gastric cancer surgeries.Furthermore,our team was invited to present two oral reports on"the application of artificial intelligence in minimally invasive gastric cancer surgery".This report aims to detail the dynamics and hotspots related to surgical treatment for gastric cancer,providing valuable references and insights for domestic surgical peers.

Delirium is an acute brain dysfunction syndrome characterized by confusion and difficulty concentrating,which mainly affects intensive care unit patients and elderly inpatients.Treatment is expensive and may also lead to increased risks of serious complications and death.The complex etiology and unknown pathological mechanisms of delirium mean that clinical drug treatment is largely ineffective.Animal models therefore provide a powerful tool to help understand the mechanism of delirium,screen new drugs,and study potential intervention measures.We review experimental research related to delirium animal models worldwide,and summarize the latest progress in the construction and evaluation of these models from the aspects of animal selection,model construction method,and model evaluation,to provide a reference for further experimental research based on delirium animal models.

Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males. Immune-checkpoint inhibitors (ICIs) that target programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive efficacy in the treatment of non-small-cell lung cancer (NSCLC) (Pardoll, 2012; Champiat et al., 2016; Gao et al., 2022). Although ICIs are usually well tolerated, they are often accompanied by immune-related adverse events (irAEs) (Doroshow et al., 2019). Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system (O'Kane et al., 2017; Puzanov et al., 2017). Compared with adverse events caused by chemotherapy, irAEs are often characterized by delayed onset and prolonged duration and can occur in any organ at any stage of treatment, including after cessation of treatment (Puzanov et al., 2017; von Itzstein et al., 2020). They range from rash, pneumonitis, hypothyroidism, enterocolitis, and autoimmune hepatitis to cardiovascular, hematological, renal, neurological, and ophthalmic irAEs (Nishino et al., 2016; Kumar et al., 2017; Song et al., 2020). Hence, we conducted a retrospective study to identify validated factors that could predict the magnitude of the risk of irAEs in patients receiving PD-1/PD-L1 inhibitors; our approach was to analyze the correlation between the clinical characteristics of patients at the start of treatment and relevant indicators such as hematological indices and the risk of developing irAEs. Then, we developed an economical, practical, rapid, and simple model to assess the risk of irAEs in patients receiving ICI treatment, as early as possible.
Male ; Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/adverse effects* ; Programmed Cell Death 1 Receptor ; Retrospective Studies ; Apoptosis

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
Animals ; Mice ; Dark Adaptation ; Light ; Retina ; Retinal Cone Photoreceptor Cells/metabolism* ; Adaptation, Ocular ; Neuroglia/physiology* ; Cell Communication ; Thyroid Hormones

Objective:The present study was designed to strengthen the education of research integrity, and to improve the awareness of academic misconduct and academic literacy of medical post-graduate students.Methods:A questionnaire survey was conducted with master post-graduate students of a university affiliated hospital, and statistical analysis on the education of research integrity and the perception of academic misconduct among the survey respondents was performed.Results:Academic master post-graduate students′ cognitions of the misconduct in scientific research process and overall academic misconduct were better than that of professional master post-graduate students, and there were significant differences ( P<0.05). The more times of participation in research integrity training, the better cognition of misconduct of scientific research process, research results publication process, and overall academic misconduct, with significant differences ( P<0.05). Conclusions:The education on scientific research integrity of medical post-graduates should be carried out systematically, while the content should be improved and the form should be enriched for scientific research integrity education, so that the medical post-graduates can have a deeper understanding of the code of academic practices, and an education model of scientific research integrity for medical post-graduate which is suitable for China′s national conditions can be gradually developed.

OBJECTIVE: To explore the effect of leucine-rich α-2-glycoprotein (LRG1) derived from hepatocytes on activation of hepatic M1 Kupffer cells. METHODS: A metabolic dysfunction-associated fatty liver disease (MAFLD) model was established in BALB/c mice by high-fat diet (HFD) feeding for 16 weeks. Oleic acid was used to induce steatosis in primary cultures of mouse hepatocytes. The mRNA and protein expressions of LRG1 in mouse liver tissues and hepatocytes were detected by real-time PCR and Western blotting. Primary hepatic macrophages were stimulated with the conditioned medium (CM) from steatotic hepatocyte along with LRG1 or transforming growth factor-β1 (TGF-β1), or both for 24 h, and the expression levels of inducible nitric oxide synthase (iNOS) was detected with Western botting, and the mRNA expressions of iNOS, chemokine ligand 1 (CXCL-1) and interleukin-1β (IL-1β) were measured by RT-PCR. The MAFLD mice were injected with LRG1 (n=6), TGF-β1 (n=6), or both (n=6) through the caudal vein, and the live tissues were collected for HE staining and immumohistochemical detection of F4/80 expression; the mRNA expressions of iNOS, CXCL-1 and IL-1β in liver tissues were detected using RT-PCR. RESULTS: The mRNA and protein expression levels of LRG1 were significantly downregulated in the liver tissues of MAFLD mice and steatotic hepatocytes (P < 0.05). Treatment of the hepatic macrophages with CM from steatosis hepatocytes significantly enhanced the mRNA expression levels of iNOS, CXCL-1 and IL-1β, and these changes were significantly inhibited by the combined treatment with TGF-β1 and LRG1 (P < 0.05). In MAFLD mice, injections with either LRG1 or TGF-β1 alone reduced hepatic lipid deposition and intrahepatic macrophage infiltration, and these effects were significantly enhanced by their combined treatment, which also more strongly inhibited the mRNA expression levels of iNOS, CXCL-1 and IL-1β (P < 0.05). CONCLUSION LRG1 inhibits hepatic macrophage infiltration by enhancing TGF-β1 signaling to alleviate fatty liver inflammation in MAFLD mice.
Animals ; Mice ; Transforming Growth Factor beta1 ; Macrophage Activation ; Signal Transduction ; Non-alcoholic Fatty Liver Disease ; Culture Media, Conditioned ; Glycoproteins

Due to the failure of multiple translational researches, Stroke Therapy Academic Industry Roundtable (STAIR) recommends the use of large animal models of focal cerebral ischemia for preclinical researches. Especially, stroke treatment has currently entered a new era of vascular recanalization. Large animals commonly used in acute ischemic stroke models include dogs, swine, sheep, and non-human primates, which can be used to simulate various aspects of cerebral ischemia and reperfusion (vascular recanalization) in patients. Although large animals have significant advantages due to their proximity to humans in anatomy and physiology, there are also issues with anatomical and physiological specificity and ethical limitations. This article summarizes the large animal ischemic stroke models prepared by craniotomy and endovascular intervention, hoping to help researchers select the most appropriate large animal ischemic stroke model, and then promote the development of stroke translational research.

Objective:To explore the short-term and long-term prognostic outcomes of anatomical liver resection(AR)for patients with perihilar cholangio-carcinoma. Methods:This is a retrospective study.All data were obtained from 4 centers,including The First Affiliated Hospital of Army Medical University,Eastern Hepatobiliary Hospital of Naval Medical University,Sichuan Provincial People's Hospital and Affiliated Hospital of Qinghai University,of a multi-center database.A total of 305 consecutive perihilar cholangiocarcinoma patients receiving radical resection between January 2013 and June 2021 were included in this study.According to the method of liver resection,all patients were divided into the AR group(n=205)and the non-anatomical liver resection(NAR)group(n=100).The baseline characteristics,short-term prognosis and long-term prognosis of the 2 groups were compared. Results:The perioperative transfusion rate and the 30-day complication rate were significantly lower in the AR group than those in the NAR group(P＜0.05).There was no statistically significant difference in the survival rates between the AR and the NAR groups(P＞0.05). Conclusion:The 2 hepatic resection modalities had no obvious effect on the long-term prognosis of perihilar cholangiocarcinoma patients after radical resection,but choosing AR tends to achieve a better short-term prognosis and is worth promoting in clinical practice.

Because the clinical studies of neuroprotective drugs ended in failure, the Stroke Treatment Academy Industry Roundtable recommended the use of non-human primates for preclinical research on stroke. Non-human primates are the bridge between basic experiment and clinical research, and the experimental results are of great reference value. However, non-human primate stroke models have a variety of neurological deficits and behavioral evaluation methods, and the scoring methods also have their own emphases. It is easy to have differences in the evaluation, or there are deficiencies in the scale itself, resulting in inaccurate scoring, which directly affects the experimental results and the implementation of subsequent research. This article summarizes the neurological deficits and behavioral evaluation methods of non-human primate stroke model.