Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

Objective Using female mice to investigate the reparative effects of human umbilical cord mesenchymal stem cells on radiation-induced ovarian injury. Methods Mice were randomly divided into three groups: a blank control group, a radiation model group, and a cell therapy group. Mice in the radiation model group and the cell therapy group received a single whole-body irradiation of 5 Gy X-rays. Within 2 hours post-irradiation, mice in the cell therapy group underwent ovarian transplantation of UC-MSCs. On days 1, 7, and 14 post-irradiation, body weight was measured, ovarian index was calculated, histopathological changes in ovarian tissue were examined, serum levels of reproductive hormones (follicle-stimulating hormone, anti-Müllerian hormone, and estradiol) were determined, and the colonization of implanted UC-MSCs in the mice was observed. Results On days 1, 7, and 14 post-irradiation, both the cell therapy group and the radiation model group showed decreased body weight compared to the blank control group (P < 0.05). On day 1 post-irradiation compared to day 1 pre-irradiation within the same group, the radiation model group exhibited a greater decrease in body weight than the cell therapy group (P < 0.05). On days 1, 7, and 14 post-irradiation, the ovarian index decreased in both the radiation model group and the cell therapy group compared to the blank control group (P < 0.05). On days 7 and 14 post-irradiation, the ovarian index in the cell therapy group was significantly higher than that in the radiation model group (P < 0.05). Ovarian tissue in the radiation model group exhibited atrophy and a reduction in the number of follicles at all stages. In contrast, follicles in the cell therapy group were large and abundant. On days 1, 7, and 14 post-irradiation, serum follicle-stimulating hormone levels in the cell therapy group were lower than those in the radiation model group, while anti-Müllerian hormone and estradiol levels were higher than those in the radiation model group (P < 0.01). In vivo fluorescence imaging demonstrated that UC-MSCs successfully colonized the ovarian tissue on days 1, 7, and 14 after transplantation. Conclusion UC-MSCs exert a repair effect on radiation-induced ovarian injury in mice.

Objective To explore the influencing factors of bone mineral density (BMD) in obese children in Qianjiang area and analyze the correlation between BMD and insulin resistance. Methods The data on pediatric cases from the outpatient department of Jianghan Oilfield General Hospital in Qianjiang from January 2018 to December 2022 were collected. A total of 183 obese children who met the inclusion and exclusion criteria were included in the study and selected in the observation group. A total of 352 children undergoing physical examination during the same period were selected as the control group. Results The body mass, waist circumference, waist to hip ratio, and BMI of obese children were significantly higher than those of the control group (P<0.001). Biochemical indexes including FBG, FINS, Home-IR, ALP, and LDL-C in obese children were significantly higher than those in the control group (P<0.05), while bone mineral density, Ca, P, sOC and HDL-C were significantly lower than those in the control group (P<0.001). The bone mineral density of obese children was significantly correlated with their exercise intensity, sunshine exposure duration, sitting time, intake of milk and dairy products, intake of sweets, supplementation of trace elements, BMI, Home-IR, and sex (all P<0.05). BMI, Home-IR, sex, exercise intensity, and sunshine exposure length were independent risk factors affecting bone mineral density of obese children (all P<0.05). Bone mineral density was negatively correlated with BMI and Home-IR (P=0.028 and0.017, respectively), and positive correlation with exercise intensity and sunlight exposure (P=0.033). Conclusion BMD of obese children in Qianjiang area is affected by gender, body mass index, diet, vitamin intake, and physical activity, and is negatively correlated with insulin resistance. Home-IR can be used as a reference for screening BMD of obese children.

Aquaporin 5(AQP5),as the main water transport protein in the body,can regulate lung diseases by regulating airway mucus secretion,pulmonary inflammation,and lung function.Programmed cell death(PCD)plays a crucial role in chronic obstructive pulmonary disease(COPD).AQP5 may affect the development of COPD by regulating PCDs.This article reviews the molecular regulatory mechanism of AQP5 on apoptosis,autophagy,iron death and pyroptosis in PCDs in recent years,and further discusses its effect on COPD in order to provide theoretical support for clinical prevention and treatment of COPD.

The expression level of NOD-like receptors(NLRP3)inflammasome is significantly elevated in breast cancer tissues,and a high level of NLRP3 inflammasomes is closely associated with breast cancer metastasis.Activation of NLRP3 inflammasome can induce the release of inflammatory factors into the tumor microenvironment(TME).These inflammatory factors,by signaling to cancer cells,reshape the TME to promote tumor growth and invasion,ultimately facilitating the process of epithelial-mesenchymal transition.This equips cancer cells with the ability to establish distant metastases and increase the formation of metastatic lesions.This review addresses the current research status and prospects of NLRP3 inflammasomes in the breast cancer TME and their role in breast cancer metastasis.The goal is to provide new insights for the study of breast cancer metastasis mechanisms and treatment strategies.

BACKGROUND:Sarcopenia is a progressive,generalized skeletal muscle disease that is closely related to the occurrence of osteoarthritis,fractures,limb disability and death in the elderly.Establishing animal models of sarcopenia is essential to understand the pathophysiology of sarcopenia and to identify effective treatment strategies. OBJECTIVE:To review the evaluation criteria of mouse models of sarcopenia and the modeling methods of mouse models of sarcopenia,and to analyze and compare the advantages and disadvantages of various modeling methods,in order to provide reference for the research and diagnosis and treatment of sarcopenia. METHODS:"Sarcopenia,skeletal muscle aging,mouse model,animal model"in Chinese and English were used as Chinese and English search terms,respectively.The search formula was"(sarcopenia OR skeletal muscle aging)AND(mouse model OR animal model)."CNKI,WanFang and PubMed were searched for related articles published from January 2010 and October 2022.A total of 59 articles were finally included for analysis. RESULTS AND CONCLUSION:There is a faster modeling time in SAMP8 mice and the type of muscle atrophy is consistent with that of patients with sarcopenia.Therefore,it is an ideal model.Although the surgical method can successfully induce muscle atrophy,it requires precise surgical operation,which is difficult and time-consuming.Hindlimb suspension modeling in mice is similar to that of the elderly and can be regarded as an effective model of senile sarcopenia.Although reagent injection molding is simple to perform,both the dose and number of days of administration of reagents are not clear and need to be further investigated.Transgenic mouse models are less commonly used and their model stability needs further study.The search for a mouse model with low cost,short time consumption and high simulation of human sarcopenia is still a future research direction.

ObjectiveTo study the effect of Tanreqing injection （TRQ） on the pulmonary flora in the rat model of chronic obstructive pulmonary disease （COPD）. MethodWistar rats were randomized into control， model， and TRQ groups. The rats in other groups except the control group were treated by smoking combined with intratracheal instillation of lipopolysaccharide for the modeling of COPD. The TRQ group was intraperitoneally injected with TRQ （2 g·kg^-1）. At the end of the experiment， after blood collection from the abdominal aorta of the rats， the lung tissue was collected for hematoxylin-eosin and picric sirius red staining to reveal the pathological changes. The lung lavage fluid was collected， and the diversity and relative abundance of lung flora in different groups were analyzed by 16S rDNA amplicon sequencing. ResultThe lungs of the control group were normal， and those of the model group showed neutrophil infiltration， telangiectasia， lung hemorrhage and emphysema in individual cases， and thickening of collagen fibers in the trachea. Compared with the model group， the TRQ group showed significantly improved lungs and recovered collagen fibers. The MLI analysis showed that compared with the control group， the model group showcased increased alveolar space （P<0.01）， which was reduced in the TRQ group （P<0.05）. Compared with the control group， the model group showed increased wall thickness （P<0.01）， and the increase was attenuated in the TRQ group （P<0.01）. TRQ increased the Simpson index and altered the α diversity of pulmonary flora. The results of principal co-ordinate analysis showed that TRQ changed the β diversity and reduced the β diversity index of pulmonary flora. At the genus level， the model group showed increased relative abundance of g_Bacillus and g_Brevundimonas and decreased relative abundance of g_Pseudomonas， compared with the control group. After treatment with TRQ， the relative abundance of g_Stenotrophomonas increased， and that of g_Bacillus decreased. The LEfSe of differential taxa between groups showed that the modeling increased the relative abundance of g_Lachnospiraceae_NK4A136_group， and TRQ treatment increased the relative abundance of g_Rhodococcus and g_Stenotrophomonas. ConclusionTRQ can regulate the diversity of pulmonary flora and restore the balance of bacterial genera in the rat model of COPD， which may be one of the mechanisms of the prevention and treatment of COPD with TRQ.

ObjectiveTo investigate the therapeutic effect of Ganmai Dazao Tang on breast cancer-related depression and explore the mechanism of the decoction in regulating immune inflammation and neurotransmitters via the mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） pathway. MethodBALB/c mice were randomized into control， model， fluoxetine （5 mg·kg^-1·d^-1）， and low- and high-dose （crude drug 20 and 40 g·kg^-1， respectively） Ganmai Dazao Tang groups （n=10）. The mouse model of 4T1 orthotopic transplantation-induced breast cancer-related depression-like behavior was established. The depression-like behavior of mice was assessed by the tail suspension test and the forced swimming test. RT-qPCR was employed to determine the mRNA levels of interleukin （IL）-17A， forkhead box P3 （FoxP3），IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in the cerebral cortex. Flow cytometry was employed to measure the proportions of immune cell subsets in the spleen and thymus. HPLC-MS/MS was employed to measure neurotransmitter levels in the cerebral cortex. Western blotting was employed to detect the activation of the MAPK/NF-κB pathway. ResultCompared with the model group， administration of Ganmai Dazao Tang at a dose of 40 g crude drug·kg^-1 continuously for 4 weeks shortened the immobility time of modeled mice in the tail suspension and forced swimming tests （P<0.05）， down-regulated the mRNA levels of IL-1β， IL-17A， and TNF-α （P<0.05）， increased the proportions of T cells， CD4⁺ T cells， B cells， helper T 17 （Th17） cells， and regulatory T （Treg） cells， and reduced the proportion of CD8⁺ T cells （P<0.05）. Furthermore， it lowered the levels of 5-hydroxyindoleacetic acid （5-HIAA） and kynurenine （Kyn）， decreased the kynurenine/tryptophan （Kyn/Trp） ratio （P<0.05）， increased the content of 5-hydroxytryptamine （5-HT）， and down-regulated the protein levels of phosphorylated extracellular signal-regulated kinase （p-ERK）， phosphorylated p38 MAPK， and phosphorylated nuclear factor-κB p65 （P<0.05）. ConclusionGanmai Dazao Tang can down-regulate the expression of inflammatory cytokines such as IL-1β， IL-17A， and TNF-α， restore 5-HT metabolism and Kyn/Trp balance， increase the 5-HT content， and reduce the activation of p38 MAPK， ERK， and the MAPK-mediated NF-κB signaling pathway to reduce neuroinflammation in the treatment of cancer-related depression.

As the global population continues to age, the incidence of Alzheimer’s disease (AD), one of the most common neurodegenerative diseases, continues to rise significantly. As the disease progresses, the patient’s daily living abilities gradually decline, potentially leading to a complete loss of self-care abilities. According to estimates by the Alzheimer’s Association and the World Health Organization, AD accounts for 60%-70% of all other dementia cases, affecting over 55 million people worldwide. The case number is estimated to double by 2050. Despite extensive research, the precise etiology and pathogenesis of AD remain elusive. Researchers have a profound understanding of the disease’s pathological hallmarks, which include amyloid plaques and neurofibrillary tangles resulting from the abnormal phosphorylation of Tau protein. However, the exact causes and mechanisms of the disease are still not fully understood, leaving a vital gap in our knowledge and understanding of this debilitating disease. A crucial player that has recently emerged in the field of AD research is the α7 nicotinic acetylcholine receptor (α7nAChR). α7nAChR is composed of five identical α7 subunits that form a homopentamer. This receptor is a significant subtype of acetylcholine receptor in the central nervous system and is widely distributed in various regions of the brain. It is particularly prevalent in the hippocampus and cortical areas, which are regions associated with learning and memory. α7nAChR plays a pivotal role in several neurological processes, including neurotransmitter release, neuronal plasticity, cell signal transduction, and inflammatory response, suggesting its potential involvement in numerous neurodegenerative diseases, including AD. In recent years, the role of α7nAChR in AD has been the focus of extensive research. Emerging evidence suggests that α7nAChR is involved in several critical steps in the disease progression of AD. These include involvement in the metabolism of amyloid β-protein (Aβ), the phosphorylation of Tau protein, neuroinflammatory response, and oxidative stress. Each of these processes contributes to the development and progression of AD, and the involvement of α7nAChR in these processes suggests that it may play a crucial role in the disease’s pathogenesis. The potential significance of α7nAChR in AD is further reinforced by the observation that alterations in its function or expression can have significant effects on cognitive abilities. These findings suggest that α7nAChR could be a promising target for therapeutic intervention in AD. At present, the results of drug clinical studies targeting α7nAChR show that these compounds have improvement and therapeutic effects in AD patients, but they have not reached the degree of being widely used in clinical practice, and their drug development still faces many challenges. Therefore, more research is needed to fully understand its role and to develop effective treatments based on this understanding. This review aims to summarize the current understanding of the association between α7nAChR and AD pathogenesis. We provide an overview of the latest research developments and insights, and highlight potential avenues for future research. As we deepen our understanding of the role of α7nAChR in AD, it is hoped that this will pave the way for the development of novel therapeutic strategies for this devastating disease. By targeting α7nAChR, we may be able to develop more effective treatments for AD, ultimately improving the quality of life for patients and their families.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.