The organoid co-culture model, as a novel tool for recreating a three-dimensional microenvironment to study cell-cell interactions, has demonstrated significant application potential in biomedical research in recent years. By simulating the in vivo tissue microenvironment, this model provides a more precise experimental platform for investigating complex cellular interactions, particularly in areas such as tumor immune evasion mechanisms, drug sensitivity testing, and the pathological characterization of neurodegenerative diseases, where it has demonstrated significant value. However, the organoid co-culture model still faces several challenges in terms of standardized procedures, large-scale cultivation, ethical guidelines, and future development. In particular, in the field of laboratory animal science, how to effectively combine organoids with traditional animal models, and how to select the most appropriate model for different research needs while exploring its potential for replacement, remain pressing issues. In the context of ethical approval and the replacement of animal experiments, the organoid co-culture model offers an experimental approach that better aligns with the "3R" principle (Replacement, Reduction, Refinement), potentially becoming an important tool for replacing traditional animal models. To this end, this paper reviews the latest advances and key challenges in this field, providing a detailed description of the construction methods for organoid co-culture models and discussing their applications in disease mechanism research and drug screening. The paper also systematically compares the organoid co-culture models with traditional animal models, exploring the criteria for selecting the appropriate model for specific applications. Furthermore, this paper discusses the potential value of organoid co-culture models as alternatives to animal experiments and anticipates future development trends of this technology. Through these discussions, the paper aims to promote the innovation and development of organoid co-culture technology and provide new perspectives and scientific evidence for future research.

The organoid co-culture model, as a novel tool for recreating a three-dimensional microenvironment to study cell-cell interactions, has demonstrated significant application potential in biomedical research in recent years. By simulating the in vivo tissue microenvironment, this model provides a more precise experimental platform for investigating complex cellular interactions, particularly in areas such as tumor immune evasion mechanisms, drug sensitivity testing, and the pathological characterization of neurodegenerative diseases, where it has demonstrated significant value. However, the organoid co-culture model still faces several challenges in terms of standardized procedures, large-scale cultivation, ethical guidelines, and future development. In particular, in the field of laboratory animal science, how to effectively combine organoids with traditional animal models, and how to select the most appropriate model for different research needs while exploring its potential for replacement, remain pressing issues. In the context of ethical approval and the replacement of animal experiments, the organoid co-culture model offers an experimental approach that better aligns with the "3R" principle (Replacement, Reduction, Refinement), potentially becoming an important tool for replacing traditional animal models. To this end, this paper reviews the latest advances and key challenges in this field, providing a detailed description of the construction methods for organoid co-culture models and discussing their applications in disease mechanism research and drug screening. The paper also systematically compares the organoid co-culture models with traditional animal models, exploring the criteria for selecting the appropriate model for specific applications. Furthermore, this paper discusses the potential value of organoid co-culture models as alternatives to animal experiments and anticipates future development trends of this technology. Through these discussions, the paper aims to promote the innovation and development of organoid co-culture technology and provide new perspectives and scientific evidence for future research.

Necroptosis is a regulated process of programmed cell death independent of aspartic acid-specific cysteine protease,which can induce inflammation.Studies have shown that necroptosis is closely related to the progression and prognosis of pancreatic disease and plays an important two-way regulatory role in its progression.Related necroptosis inhibitors and inducers are expected to be used in the treatment of pancreatic disease.We herein review the mechanism of necroptosis and its role in the progression of pancreatic disease to provide a new understanding of the pathogenesis and treatment of pancreatic diseases and offer a theoretical basis for the research and development of targeted drugs.

Prostate cancer is a prevalent malignant tumor in the male genitourinary system,characterized by a high propensity for bone metastasis.It is a leading cause of mortality,with approximately 70％of deaths attributed to this form of metastasis.Mouse models provide a crucial tool in the investigation of prostate cancer bone metastasis,and play a pivotal role in elucidating the underlying pathophysiological mechanisms and in the development and assessment of therapeutic agents.In this review,we summarize research progress in the construction method and evaluation strategies used in establishing prostate cancer bone metastasis mouse models.Notably,this review focuses on the exploration of the mechanisms responsible for prostate cancer bone metastasis,using mouse models,with the aim of offering insights and serving as a valuable reference for prostate cancer bone metastasis.

Objective To systematically study the efficacy and safety of KRAS^G12C inhibitors in advanced solid tumors with KRAS^G12C-mutated. Methods Computer searches from PubMed, The Cochrane Library, Web of Science, Embase, CNKI, and CBM databases were conducted to collect clinical studies on KRAS^G12C inhibitors in advanced solid tumors with KRAS^G12C-mutated, with a search time from inception to October 12, 2022. Then, two investigators independently screened the literature, extracted information, assessed the risk of bias in included studies, and performed meta-analyses using RevMan 5.4 software. Results There were four publications included, all of which were single-arm clinical studies. The KRAS^G12C inhibitors that completed clinical phase Ⅰ and Ⅱ trials were sotorasib and adagrasib, with two publications each. A total of 388 and 394 patients were included in the efficacy evaluation and safety evaluation, respectively. Resultsof the Meta-analysis showed that the patients had objective response rate, overall disease control, and disease stabilization rates of 35%, 82%, and 45%, respectively. In addition, the rate of serious adverse events, general adverse events, and all adverse events in patients was 2%, 28%, and 79%, respectively. Moreover, the rate of partial remission of disease in NSCLC patients was 38%. Conclusion The KRAS^G12C inhibitors sotorasib and adagrasib exhibited good efficacy and high safety in advanced solid tumors.

Objective To explore the effects of ginsenoside Rg1 on blood-brain barrier, neuroinflammation and behavioral function of traumatic brain injury (TBI) mouse model.MethodsThe experiment was divided into two parts. In the first part, 27 SPF male BALB/c mice were randomly divided into blank group, sham operation group and TBI model group, with 9 mice in each group. TBI model group was made by controlled cortical impact (CCI) after craniotomy, while sham operation group was only performed craniotomy without any treatment, and the blank group was not treated at all. The effect of modeling was evaluated after operation. In the second part, 50 male BALB/c mice were randomly divided into sham operation group, three different drug dosage groups and solvent (DMSO) control group, with 8 mice in each group. The drug treatment groups were injected with ginsenoside Rg1 at the doses of 10, 20 and 40 mg/kg respectively 6 hours after TBI model had been successfully established, while the DMSO control group was given the same amount of 1% DMSO for one week, twice a day. Modified neurological severity scores (mNSS) were performed on the 1st, 3rd, 7th and 14th day after modeling, and the blood-brain barrier leakage was detected by Western blotting on the 3rd day after modeling. On the 14th and 16th day, the elevated cross maze test and water maze test were used to detect the neurobehavioral function. On the 28th day after anesthesia and perfusion, the brains were taken out, and the neuroinflammation such as activation of microglia and astrocytes was observed by immunofluorescence staining.ResultsThe expression level of MMP-9, a marker of blood-brain barrier, decreased in ginsenoside Rg1 treatment group (P<0.01). The number of microglia （Iba-1 positive) and astrocyte (GFAP positive) cells decreased significantly (P<0.05), which indicated that neuroinflammation was inhibited, and the best effect was achieved at the dosage of 20 mg/kg (P<0.01). The mNSS of mice in ginsenoside Rg1 treatment group were significantly lower than those in DMSO control group (P < 0.01), and the proportion of times they entered the open arm was significantly higher than that in DMSO control group (P < 0.05). The time ratio in the quadrant where the water maze experimental platform was located and the times of crossing the platform were significantly higher than those in control group (P < 0.05), and the dosage of 20 mg/kg had the best effect.ConclusionThe TBI mouse model was successfully constructed and applied to the study of ginsenoside Rg1 repair of mouse traumatic brain injury. Ginsenoside Rg1 can significantly improve blood-brain barrier, alleviate neuroinflammation and improve neurobehavioral function in TBI model mice, and the effect is the most significant at the dose of 20 mg/kg.

Objective:To explore the risk factors of pneumoconiosis patients' re-admission to provide a scientific basis for improving the treatment effect of pneumoconiosis, reducing the rate of re-admission, and reducing the burden of disease.Methods:In June 2020, The clinical data of 470 patients with pneumoconiosis who had hospitalization records from February 8, 2014, to February 8, 2020, in the Hunan Provincial Occupational Disease Prevention and Treatment Institute were retrospectively analyzed. The patients' general data and emotional state at the first admission were collected through questionnaires and telephone follow-ups. The entire group of patients completed at least one follow-up, with readmission as the end event. First, the Kaplan-Meier method was used for univariate analysis. The multivariate COX regression model analysis was performed on meaningful variables to explore the risk factors that affect the patient's re-admission.Results:A total of 470 patients with pneumoconiosis were included in this study, with an average age of 55.88 years (34-81 years old) and all the participants were male. During the first admission, the number of participants diagnosed as stage III pneumoconiosis, with complications of COPD, fatty liver, or severe pulmonary diffusion dysfunction was 215 (45.74%) , 179 (38.09%) , 51 (10.85%) , and 44 (9.36%) , respectively. Six patients (1.28%) have had suicidal tendencies almost every day since they became ill. A total of 345 patients (73.40%) were re-admitted to the hospital. Multivariate Cox regression model analysis showed that compared with the suspected pneumoconiosis group, patients in the first, second, and third-stage pneumoconiosis groups had an increased risk of readmission ( OR=2.43, 2.96, 2.35, P=0.000) . Compared with the age of 30-50 years old, 50-70 years old and ≥70 years old have an increased risk of readmission ( OR=1.28, 2.32, P<0.05) . Patients with tricuspid regurgitation ( OR=1.33, P<0.05) and elevated triglyceride level (>2.26 mmol/L) ( OR=1.40, P<0.05) have increased risks of readmission. Compared with the normal group, patients with severe pulmonary diffusion dysfunction in pneumoconiosis have an increased risk of readmission ( OR=1.96, P<0.05) . Compared with the normal group, pneumoconiosis patients in the suicidal group had an increased risk of re-admission to the hospital almost every day ( OR=2.92, P<0.05) . Conclusion Age of onset, stage of pneumoconiosis, tricuspid regurgitation, high triglycerides, severe diffuse pulmonary dysfunction, and suicidal tendency are independent risk factors that affect the readmission of patients with pneumoconiosis. The management of chronic diseases and mental health of patients with pneumoconiosis should be strengthened to reduce the risk of readmission. Conclusion:Age of onset, stage of pneumoconiosis, tricuspid regurgitation, high triglycerides, severe diffuse pulmonary dysfunction, and suicidal tendency are independent risk factors that affect the readmission of patients with pneumoconiosis. The management of chronic diseases and the mental health of patients with pneumoconiosis should be strengthened to reduce the risk of readmission.

Objective:To explore the risk factors of pneumoconiosis patients' re-admission to provide a scientific basis for improving the treatment effect of pneumoconiosis, reducing the rate of re-admission, and reducing the burden of disease.Methods:In June 2020, The clinical data of 470 patients with pneumoconiosis who had hospitalization records from February 8, 2014, to February 8, 2020, in the Hunan Provincial Occupational Disease Prevention and Treatment Institute were retrospectively analyzed. The patients' general data and emotional state at the first admission were collected through questionnaires and telephone follow-ups. The entire group of patients completed at least one follow-up, with readmission as the end event. First, the Kaplan-Meier method was used for univariate analysis. The multivariate COX regression model analysis was performed on meaningful variables to explore the risk factors that affect the patient's re-admission.Results:A total of 470 patients with pneumoconiosis were included in this study, with an average age of 55.88 years (34-81 years old) and all the participants were male. During the first admission, the number of participants diagnosed as stage III pneumoconiosis, with complications of COPD, fatty liver, or severe pulmonary diffusion dysfunction was 215 (45.74%) , 179 (38.09%) , 51 (10.85%) , and 44 (9.36%) , respectively. Six patients (1.28%) have had suicidal tendencies almost every day since they became ill. A total of 345 patients (73.40%) were re-admitted to the hospital. Multivariate Cox regression model analysis showed that compared with the suspected pneumoconiosis group, patients in the first, second, and third-stage pneumoconiosis groups had an increased risk of readmission ( OR=2.43, 2.96, 2.35, P=0.000) . Compared with the age of 30-50 years old, 50-70 years old and ≥70 years old have an increased risk of readmission ( OR=1.28, 2.32, P<0.05) . Patients with tricuspid regurgitation ( OR=1.33, P<0.05) and elevated triglyceride level (>2.26 mmol/L) ( OR=1.40, P<0.05) have increased risks of readmission. Compared with the normal group, patients with severe pulmonary diffusion dysfunction in pneumoconiosis have an increased risk of readmission ( OR=1.96, P<0.05) . Compared with the normal group, pneumoconiosis patients in the suicidal group had an increased risk of re-admission to the hospital almost every day ( OR=2.92, P<0.05) . Conclusion Age of onset, stage of pneumoconiosis, tricuspid regurgitation, high triglycerides, severe diffuse pulmonary dysfunction, and suicidal tendency are independent risk factors that affect the readmission of patients with pneumoconiosis. The management of chronic diseases and mental health of patients with pneumoconiosis should be strengthened to reduce the risk of readmission. Conclusion:Age of onset, stage of pneumoconiosis, tricuspid regurgitation, high triglycerides, severe diffuse pulmonary dysfunction, and suicidal tendency are independent risk factors that affect the readmission of patients with pneumoconiosis. The management of chronic diseases and the mental health of patients with pneumoconiosis should be strengthened to reduce the risk of readmission.

Objective: To analyze the research hotspots of transitional care in patients with heart failure, and to provide reference for the development of related research in China. Methods: Based on the literature on transitional care for heart failure patients included in the Web of Science database, Use CiteSpace software to visualize research institutions, core journals, cited documents, and high-frequency keywords. Results: The current research in the field of transitional care for patients with international heart failure is mainly concentrated in colleges and universities in the United States. The core publications include Journals of The American Geriatrics Society and Bmc Health Services Research. Through keyword co-occurrence cluster analysis, the international hot topics of transitional care and discharge plan, readmission risk, quality improvement and quality of life in patients with heart failure were explored. Conclusion Hong Kong's transitional care research in patients with heart failure is more in-depth. Although the academic research of mainland China has increased, it has not yet reached the international frontier and needs further development and improvement.

OBJECTIVETo observe the difference in the clinical therapeutic effects on bronchial asthma in children of different body constitutions treated withplaster andplaster.

METHODSOne hundred and twenty-two children of bronchial asthma were divided into three groups according to TCM body constitutions, 42 cases in thedeficiency constitution group, 40 cases in thedeficiency constitution group and 40 cases in the phlegm damp constitution group. From 2011 to 2013, the acupoint plaster was applied to all of the children in the three groups during the dog days and the third nine-day period after the winter solstice each year. The average attack frequency and onset days of bronchial asthma and relevant immune function indicators were observed during treatment and 1 year after treatment in the children and the therapeutic effects were evaluated.

RESULTS①In 2014, the acute attacks of bronchial asthma were (1.2±0.9) times and (1.4±0.4) times in thedeficiency constitution group and thedeficiency constitution group, all lower than (3.0±0.5) times in the phlegm damp constitution group (both<0.05) separately. ②After treatment, in thedeficiency constitution group anddeficiency constitution group, the values of IgG, IgA and IgM were all increased as compared with those before treatment (all<0.05). ③The total effective rate was over 95% in the children of the three groups. The clinical control rates in thedeficiency constitution group and thedeficiency constitution group were higher apparently than that in the phlegm damp constitution group, indicating the significant difference statistically (both<0.05).

CONCLUSIONSThe combined treatment ofplaster andplaster are effective on bronchial asthma in the children of different body constitutions. The therapeutic effects for thedeficiency constitution and thedeficiency constitution are more apparent than that for the phlegm damp constitution.