BACKGROUND:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.

This review summarizes the applications and advancements of artificial intelligence(AI)in the analysis of retinal vascular parameters. Retinal vascular parameters, including vessel diameter, fractal dimension, vascular tortuosity, branching angles, and vessel density, are important indicators for assessing changes in the retinal vascular network structure. These parameters are not only related to various ophthalmic diseases but also reflect the conditions of systemic diseases such as diabetes and Alzheimer's disease. This article provides a detailed discussion on the advantages of AI technology in the automated identification and quantification of retinal vascular parameters, particularly in improving measurement efficiency and accuracy, and enabling the early detection and monitoring of various diseases. Additionally, the challenges faced by AI in the analysis of retinal vascular parameters were discussed, such as data standardization and insufficient sample diversity, and proposes directions for future research. By thoroughly analyzing the application of AI in retinal vascular parameter analysis, this article aims to offer new perspectives and methods for clinical diagnosis and early intervention of diseases, holding significant clinical significance and application prospects.

ObjectiveTo explore the potential mechanism of Dingchuan Granule （定喘颗粒， DG） in the treatment of respiratory syncytial virus （RSV） pneumonia. MethodsA total of 60 male Sprague Dawley （SD） rats were randomly divided into control group， model group， ribavirin group， DG low-dose group， DG middle-dose group， and DG high-dose group， with 10 rats in each group. Except for the control group， rats were administrated with RSV via intranasal drip. After model establishment， the DG low-， middle-， and high-dose groups were administrated via oral gavage with DG at 3.47， 6.93， and 13.86 g/（kg·d） respectively， while the ribavirin group was administrated via oral gavage with ribavirin at 15.75 mg/（kg·d）. The drug was given once daily for one week. The rats in the control group and the model group were not given any drug， only subjected to the grasping action. Twenty-four hours after the last administration， the pathological changes of lung tissues were observed and scored using HE staining. The levels of serum inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）， were detected by colorimetry. The protein levels of nuclear factor （erythroid derived 2）-like 2 （Nrf2）， Kelch-like ECH-associated protein 1 （Keap1）， heme oxygenase 1 （HO-1）， and NAD（P）H quinone dehydrogenase 1 （NQO1） in lung tissues were measured by Western Blot. The RSV load as well as the gene expression levels of Nrf2， Keap1， HO-1， and NQO1 in lung tissues were determined by qRT-PCR. The level of reactive oxygen species （ROS） in rat lung tissues was detected using chemiluminescence. The levels of glutathione （GSH） and malondialdehyde （MDA） in rat lung tissues were measured by a microassay. ResultsCompared with the control group， other groups had significant increases in pathological score of lung tissue， RSV load， levels of ROS， MDA， serum TNF-α， IL-1β， and IL-6； decrease in GSH level， increases in expression level of Keap1 protein and its mRNA in lung tissue， and significant decrease in levels of Nrf2， HO-1， expression level of NQO1 protein and its mRNA （P＜0.05）. Compared with the model group， all the above-mentioned indicators in the DG low-， middle-， and high-dose groups and the ribavirin group were improved to varying degree （P＜0.05）. The levels of serum TNF-α， IL-1β， and IL-6 in rats of DG dose groups showed a dose-dependent pattern， the DG high-dose group exhibiting the best effect （P＜0.05）. The DG high-dose group was superior to the DG low- and middle-dose groups in reducing the levels of ROS and MDA， and increasing the level of GSH in lung tissues （P＜0.05）. The DG high-dose group and the ribavirin group had better effect than the DG middle-dose group in reducing the RSV load （P＜0.05）. The DG high-dose group was superior to the ribavirin group in improving the protein levels of Nrf2， Keap1， HO-1， and NQO1 （P＜0.05）. ConclusionDG could inhibit oxidative stress by regulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway to improve pulmonary inflammation and treat RSV pneumonia， with the DG high-dose group showing the best effect.

ObjectiveThe effects of two microbial fertilizers （Bacillus subtilis fertilizer and Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer） on the growth and development， the accumulation of active ingredients， and the microbial community diversity of rhizosphere soil of Atractylodes chinensis were investigated. MethodsA field experiment was carried out with two-year-old Atractylodes chinensis as the test material. Plant samples were collected during the wilt stage （September 26， 2023） to determine the general agronomic traits of Atractylodes chinensis. High-performance liquid chromatography （HPLC） was utilized to evaluate the effects of microbial fertilizers on the synthesis and accumulation of four active ingredients （atractylodin， atractylon， β-eudesmol， and atractylenolide Ⅰ） in Atractylodes chinensi. PacBio Sequel sequencing technology was used to explore the differences in bacterial community structures and diversity in the rhizosphere soil of Atractylodes chinensis treated with different microbial fertilizers. ResultsThe two microbial fertilizers had significant growth-promoting effects on Atractylodes chinensis. Compared with those of the CK group， the stem diameter， stem and leaf dry and fresh weight， and rhizome dry and fresh weight of Atractylodes chinensis significantly increased by 0.47-1.07 times （P<0.05） after the application of the Bacillus subtilis fertilizer （16 kg/667 m²）， and those significantly increased by 0.62-0.96 times （P<0.05） after the application of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer （1.5 kg/667 m²）. The effect on plant height was not significant. The application of two microbial fertilizers was beneficial to the accumulation of atractylodin， atractylon， β-eudesmol， and atractylenolide Ⅰ （P<0.01）， and the effect of the Bacillus subtilis fertilizer on the accumulation of active ingredients of Atractylodes chinensis was better than that of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. The results of high-throughput sequencing showed that compared with the CK group， the Bacillus subtilis fertilizer （8 kg/667 m²） could significantly increase the diversity of rhizosphere bacterial species by regulating the Simpson index and Shannon index （P<0.05）， and the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer significantly reduced the bacterial diversity （P<0.05）. The relative abundance of dominant bacteria was compared at the phylum and genus levels. The relative abundance of Proteobacteria （45.73%） and Burkholderia_Caballeronia_Paraburkholderia （9.98%） significantly increased after the application of the Bacillus subtilis fertilizer （P<0.01）， and the relative abundance of Acidobacteriota （20.53%） and Sphingomonas （3.63%） increased significantly （P<0.01） after the application of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. The relative abundance of beneficial bacteria in the Bacillus subtilis fertilizer was slightly higher than that in the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. Pearson correlation analysis showed that Burkholderia_Caballeronia_Paraburkholderia and Sphingomonas were positively correlated with the content of atractylodin， atractylon， β-eudesmol， and atractylenolide Ⅰ （P<0.05）. ConclusionThe application of the Bacillus subtilis fertilizer and Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer can increase the yield of medicinal materials and promote the synthesis and accumulation of active ingredients by regulating the rhizosphere microecological diversity of Atractylodes chinensis， and the application effect of the Bacillus subtilis fertilizer is better than that of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer.

Objective: To investigate the therapeutic efficacy and potential mechanisms of fecal microbiota transplantation (FMT) in patients with type 2 diabetes mellitus (T2DM), and to preliminarily identify the traditional Chinese medicine (TCM) syndrome element characteristics of FMT in the treatment of T2DM. Methods: Between March 25, 2023 and September 30, 2024, T2DM patients who met the inclusion and exclusion criteria were enrolled at the Department of Rheumatology and Endocrinology of the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine. Participants received oral microbiota capsules as an adjunct to metformin therapy. Information obtained by four diagnostic methods of TCM, along with clinical and laboratory parameters, was collected before and after the intervention. Metagenomic sequencing was employed to analyze the gut microbiota, and Spearman correlation analysis was used to explore the relationship between laboratory indicators and differential bacterial genera. According to the post-treatment reduction in glycosylated hemoglobin (HbA1c), patients were categorized into a response (R) group and a non-response (NR) group. Treatment outcomes, safety indicators, gut microbiota changes, and TCM syndrome element features were compared between the two groups. Results: A total of 53 T2DM patients were included in the final analysis, and 30 patients were assigned to R group and 23 to NR group. After treatment, the R group exhibited significant reductions in HbA1c, fasting plasma glucose (FPG), and 2-hour postprandial glucose (2hPG) (P < 0.05 or P < 0.01). The NR group also showed significant decreases in HbA1c and FPG levels P < 0.01 or P < 0.05. Compared with the NR group, after treatment, FPG level in the R group demonstrated significant reductions (P < 0.01). As compared with before treatment, pancreatic islet function demonstrated enhancement in the R group, a significant increase in the 2-hour pastprandial C-peptide (2hC-P) levels in R group (P < 0.05), whereas no marked change was observed in the NR group. Regarding body composition indicators, the R group showed significantly lower waist-hip ratio (WHR), visceral fat (VF), and subcutaneous fat (SF) levels compared with the NR group (P < 0.01). After treatment, the NR group exhibited a significant elevation in aspartate aminotransferase (AST) levels (P < 0.05). Other safety-related indicators fluctuated within normal reference ranges, and no other adverse events, such as diarrhea, fever, or nausea, were reported. Metagenomic sequencing showed that FMT improved the diversity and richness of the gut microbiota, remodeling its overall structure. At the phylum level, the abundance of p_Firmicutes decreased significantly (P < 0.01), while the abundances of p_Bacteroidota and p_Proteobacteria increased significantly (P < 0.01). At the family level, among the 125 identified taxa, the abundances of f_Bacteroidaceae, f_Lactobacillaceae, and f_Sutterellaceae were significantly elevated, whereas six families, including f_Lachnospiraceae, f_Ruminococcaceae, and f_Coriobacteriaceae, were significantly decreased (all P < 0.05). Among the 367 taxa at the genus level, the top 10 differential genera showed significantly increased abundances of g_Bacteroides and g_Sutterella, and significantly decreased abundances in eight genera, including g_Faecalibacterium, g_Ruminococcus, g_Blautia, and g_Collinsella (all P < 0.05). Correlation analysis suggested that the phylum p_Bacillota was positively correlated with improvements in T2DM laboratory parameters, g_norank_f_Prevotellaceae was significantly positively correlated with fasting C-peptide (FC-P) and 2hC-P (P < 0.05). HbA1c demonstrated a significantly positive correlation with g_Blautia and g_Gemmiger (P < 0.05) and a significantly negative correlation with g_Bacteroides and g_Collinsella (P > 0.05). Analysis of syndrome element characteristics revealed that the R group was primarily characterized by pathological patterns of dampness, phlegm, and Yang deficiency. Before treatment, statistically significant reductions in syndrome element scores were observed for dampness, Yang deficiency, spleen, phlegm, Qi deficiency, Qi stagnation, and Yin deficiency (P < 0.01), as well as for heat and liver (P < 0.05). The NR group was mainly featured with Qi deficiency and Yin deficiency. Statistically significant changes in their syndrome element scores after treatment were noted for Qi deficiency (P < 0.01), and for spleen, Qi stagnation, liver, and blood deficiency (P < 0.05). In this group, the score changes for Yang deficiency, Yin deficiency, heat, and dampness were not statistically significant (P > 0.05). Conclusion The principles of syndrome element differentiation can be effectively applied to predict treatment efficacy and facilitate patient selection for FMT in the treatment of T2DM. Patients with T2DM presented with specific TCM syndrome element characteristics, notably dampness, phlegm, and Yang deficiency, represent a highly responsive population to FMT therapy.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

Glucosidases are an indispensable class of enzymes in the sugar metabolism of organisms. To investigate the biological functions and expression patterns of α-glucosidases (AGLUs) and β-glucosidases (BGLUs), we identified the two family members in the genome of melon (Cucumis melo). The number, location on chromosomes, gene structure, subcellular localization, conserved motifs, and phylogenetic relationship of the two family members were analyzed. Based on the cis-acting elements in the promoter region and protein interaction models, their functions were preliminarily predicted. Furthermore, the gene expression of the two family members was determined by qRT-PCR. The results showed that the melon genome contained five AGLU family members on five chromosomes, and all of the five members were located in the extracellular matrix, with the amino acid sequence lengths ranging from 899 aa to 1 060 aa. The melon genome carried 18 BGLU family members on 8 chromosomes, and all the members were located in the cell membrane or cytoplasm, with the amino acid lengths ranging from 151 aa to 576 aa. The qRT-PCR results showed that the expression of about 50% of the genes was down-regulated upon cold stress. CmAGLU5 and CmBGLU7 may be key members of the two families, respectively, in response to cold stress. The expression of all members of the two families was up-regulated under abscisic acid (ABA), high salt, and drought stress. In the AGLU family, CmAGLU3 was the key gene in response to ABA and high salt stress, while CmAGLU4 was the key gene in response to drought stress. In the BGLU family, CmBGLU18 was the key gene in response to ABA, while CmBGLU6 was the key gene in response to high salt and drought stress.
beta-Glucosidase/metabolism* ; Phylogeny ; alpha-Glucosidases/metabolism* ; Gene Expression Regulation, Plant ; Cucurbitaceae/enzymology* ; Multigene Family ; Cucumis melo/enzymology* ; Stress, Physiological

Objective To investigate the relationship between intraoperative central venous pressure(CVP)and postoperative acute kidney injury(AKI)in off-pump coronary artery bypass grafting(OPCABG).Methods A retrospective analysis was conducted,collecting clinical data from patients who underwent OPCABG at the General Hospital of Northern Theater Command of the Chinese People's Liberation Army between 2018 and 2021,and at the Second Affiliated Hospital of Dalian Nedical University between 2019 and 2022.Preoperative,intraoperative,and postoperative data were gathered using electronic medical record and anesthesia systems.The patients were divided into two groups according to whether AKI occurred within 7 days after surgery:AKI group and non-AKI group.The receiver operating characteristic(ROC)curve of intraoperative average CVP and postoperative AKI was plotted to determine the optimal cut-off value of intraoperative average CVP.Multivariate logistic regression analysis was used to assess the corre-lation between intraoperative average CVP and postoperative AKI.Results AKI occurred in 400 patients(34.9％).Compared with the non-AKI group,the age was older(P＜0.05),the BMI and serum creati-nine levels,the proportion of insulin therapy among patients with preoperative hypertension and diabetes,the average CVP,and the incidence of acute hypotensive episodeswas higher(P＜0.05),the intraoperative urine output was significantly reduced(P＜0.05),and the duration of hypotension was lon-ger(P＜0.05)in the AKI group.After fully adjusting for demographics,preoperative comorbidities,and intraoperative variables such as medication use and other covariates,each 1 mmHg increase in intraoperative average CVP was associated with a 1.47-fold increase in the odds of developing AKI(OR=1.47,95％CI 1.36-1.59,P＜0.001).The ROC curve identified 10.11 mmHg as the optimal cutoff value for intraopera-tive average CVP.Patients with an intraoperative average CVP≥10.11 mmHg had a 4.14-fold higher risk of developing postoperative AKI compared to those with CVP＜10.11 mmHg.Conclusion Elevated intrao-perative average CVP(≥10.1 mmHg)is independently associated with a higher risk of postoperative AKI in OPCABG.

Objective:To investigate the status of personnel, facilities, and technology of radiation therapy in Henan province in 2023.Methods:A unified online survey questionnaire was designed and distributed from March to April 2023 by the Henan Cancer Diagnosis and Treatment Quality Control Center to various medical institutions throughout the province to investigate the personnel, radiotherapy equipment, quality control equipment, imaging equipment, and radiotherapy technology development of each radiotherapy unit. Descriptive statistical methods were mainly used.Results:As of April 30, 2023, there were a total of 168 units engaged in radiation therapy in Henan province. The number of physicians involved in radiation therapy was 956, along with 365 medical physicists and 680 technicians. The equipment inventory included 212 medical linear accelerators, 1 cobalt-60 therapy machine, 32 afterloading therapy apparatuses, 4 Cyber Knife, 173 CT simulators, 2 MRI simulators and 94 conventional simulators. Linear accelerators were the primary radiotherapy equipment, 2.15 units per 1 million population on average. Additionally, there were 11 units offering 2D radiotherapy, 24 units offering 3D conformal radiotherapy, 130 units offering intensity-modulated radiotherapy, 41 units offering rotational intensity-modulated radiotherapy, and 33 units offering stereotactic radiosurgery. Regarding physical quality control equipment, 16 units were equipped with three-dimensional water tanks, 162 units were equipped with radiation dose meters, 114 units were equipped with morning check meters, 60 units were equipped with film dose meters, and 108 units were equipped with intensity adjustment plan verification systems.Conclusions:In 2023, there is a shortage of radiation therapy professionals in Henan province. Disparities are observed in the distribution of radiation therapy equipment among regions. Intensity-modulated radiotherapy has become the mainstream technology for radiation therapy in Henan province. The configuration of radiation therapy quality control equipment and standardized quality control work should be further improved.