ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

Objective:To identify candidate strains of Nontoxigenic Clostridioides difficile (NTCD) with potential for intervention in Clostridioides difficile infection (CDI) and analyze their phenotypic characteristics. Methods:A total of 713 Clostridioides difficile strains from various sources were systematically collected nationwide between 2015 and 2023. This included 649 strains isolated from human fecal samples and 64 strains isolated from the fecal samples of farmed animals. NTCD strains were preliminarily screened through toxin gene detection and antibiotic sensitivity test, and then NTCD candidate strains with potential for intervention in CDI were screened by a series of in vitro experiments, including MLST, sporulation, germination, adhesion, motility, and biofilm formation ability. Ultimately, the virulence genes and antimicrobial resistance genes of the candidate strains were comprehensively analyzed to rigorously assess their safety profiles. Results:Among 713 strains of C. difficile from different sources, 10 strains were initially screened out, which were non-toxin-producing and sensitive to antibiotics. MLST showed that seven strains were from the Clade1 branch and three strains were of a novel type. The results of sporulation and germination showed that SD59, SD178, SJZ17, and WZ142 had stronger sporulation and germination abilities. The adhesion of 10 strains was high, and the adhesion rate was between 72.93% and 99.32%. The motility of all strains was different, and the motility of SD178, SD59 and SJZ17 was stronger. The biofilm-forming ability of all strains was weak. SD59, SD178 and SJZ17 carried a limited number of virulence and resistance genes, thereby posing a relatively low safety risk. Conclusion:Three NTCD strains are successfully selected as potential effective NTCD strains to interfere with CDI.

Objective:To identify candidate strains of Nontoxigenic Clostridioides difficile (NTCD) with potential for intervention in Clostridioides difficile infection (CDI) and analyze their phenotypic characteristics. Methods:A total of 713 Clostridioides difficile strains from various sources were systematically collected nationwide between 2015 and 2023. This included 649 strains isolated from human fecal samples and 64 strains isolated from the fecal samples of farmed animals. NTCD strains were preliminarily screened through toxin gene detection and antibiotic sensitivity test, and then NTCD candidate strains with potential for intervention in CDI were screened by a series of in vitro experiments, including MLST, sporulation, germination, adhesion, motility, and biofilm formation ability. Ultimately, the virulence genes and antimicrobial resistance genes of the candidate strains were comprehensively analyzed to rigorously assess their safety profiles. Results:Among 713 strains of C. difficile from different sources, 10 strains were initially screened out, which were non-toxin-producing and sensitive to antibiotics. MLST showed that seven strains were from the Clade1 branch and three strains were of a novel type. The results of sporulation and germination showed that SD59, SD178, SJZ17, and WZ142 had stronger sporulation and germination abilities. The adhesion of 10 strains was high, and the adhesion rate was between 72.93% and 99.32%. The motility of all strains was different, and the motility of SD178, SD59 and SJZ17 was stronger. The biofilm-forming ability of all strains was weak. SD59, SD178 and SJZ17 carried a limited number of virulence and resistance genes, thereby posing a relatively low safety risk. Conclusion:Three NTCD strains are successfully selected as potential effective NTCD strains to interfere with CDI.

Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

Objective This study aimed to investigate the levels of non-enzymatic antioxidants among patients with depression at different age stages.Methods One hundred thirty five patients with depression(including 63 elderly patients aged 60 years and older,and 72 young and middle-aged patients under 60 years old)and 98 healthy controls(including 46 elderly controls aged 60 years and older,and 52 young and middle-aged controls aged under 60 years old)were enrolled.Serum levels of non-enzymatic antioxidants(uric acid,total bilirubin,albumin)were assessed.Results Multiple analysis of variance showed the main effects of depression factors on uric acid and total bilirubin were significant(P<0.05).Uric acid[(314.30±85.18)μmol/L vs.(339.68±85.27)μmol/L],total bilirubin[(12.81±6.16)μmol/L vs.(15.09±5.97)μmol/L]levels were lower in patients with depression than in controls(P<0.05).There was an interactive effect between age and depression factors on the levels of albumin(P<0.001),and the levels of albumin[(41.05±3.97)g/L vs.(46.01±4.49)g/L]were lower in group of the elderly patients with depression than those in group of the young and middle-aged patients with depression(P<0.01).Conclusion Patients with depression have abnormalities in levels of non-enzymatic antioxidants which are more severe in elderly patients.

Guillain-Barre syndrome rarely develops after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and only a few reports exist in China. Guillain-Barre syndrome is an acute and life-threatening condition that requires early diagnosis and treatment. A patient with acute myeloid leukemia underwent allogeneic HSCT for >5 months and gradually developed limb muscle weakness and limited eye movement after coexisting with delayed acute intestinal graft-versus-host disease. After the examination of cerebrospinal fluid and electromyography, the diagnosis of Guillain–Barre syndrome was confirmed. After a high-dose intravenous immunoglobulin (IVIg) treatment, muscle strength gradually recovered, and the prognosis was good.

The onset of myasthenia gravis (MG) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) seriously threatens the survival of patients, since it is acute, and is prone to rapid progression. Two patients with acute myeloid leukemia (AML), who had undergone allo-HSCT developed shortness of breath, and gradually developed cervical weakness and dyspnea. The acetylcholine receptor (AChR) antibody and neostigmine test enabled the diagnosis of MG. The condition of the patients improved after treatment with pyridostigmine bromide, glucocorticoids and rituximab.

Objective:To understand molecular characteristics and antibiotic resistance of Clostridioides ( C.) difficile isolated from children in China, and provide data support the development of disease risk assessment and burden studies. Methods:A total of 155 strains of C. difficile isolated from children aged <12 years in 14 provinces (autonomous regions, municipalities) in China from 2010 to 2023 were used for the analyses on molecular characteristics and antibiotic resistance of C. difficile by PCR and drug susceptibility test. Results:A total of 26 sequence types (STs) and 18 ribotypes (RTs) were identified in the 155 C. difficile isolates, in which ST3 (20.65%), ST54 (16.13%), ST35 (12.90%), and RT012/ICDC007 (14.84%), RT001/ICDC001 (11.61%), RT046/ICDC018 (8.39%) were the most common. One highly virulent strain with RT078 and 27 non-toxin-producing strains were also found; the predominant toxin gene was tcdA+ tcdB+ cdt-. All the strains were sensitive to metronidazole and vancomycin, and there were 29 multidrug-resistant strains, in which 1 strain was resistant to all the seven antibiotics except for vancomycin and metronidazole. Conclusions:Molecular characteristics and antibiotic resistance of C. difficile in children were similar to those in whole population in China, but there were regional distribution differences. It is necessary to strengthen the routine drug-resistance surveillance for C. difficile infection in children in China.

Low-intensity pulsed ultrasound(LIPUS)is a low-cost,non-invasive and safe treatment method mainly used for musculoskeletal diseases,especially for fractures and nonunion.This article reviews the therapeutic effects of LIPUS on various musculoskeletal and nervous system diseases and analyzes its mechanism and potential targets.It is found that besides fracture and nonunion,LIPUS also has clinical application prospect in treating osteoporosis,muscle injury,and motor nervous system diseases.

Objective:To investigate the role of IL-21/IL-21R-mediated CD4 + T cells in Chlamydia muridarum ( Cm) respiratory infection. Methods:C57BL/6 mice (WT mice) and IL-21R -/- mice were used to establish the models of Cm respiratory infection through intranasal inhalation of Cm. Flow cytometry was used to detect the proportion, number, activity and function of CD4 + T cells in lung and spleen tissues at 0, 3, 7 and 14 d after Cm respiratory tract infection. IFN-γ and IL-4 levels in spleen cell culture supernatants were detected by ELISA. Na?ve WT mice were transferred with CD4 + T cells in the spleen tissues of IL-21R -/- mice or WT mice on 7 d after infection and given Cm intranasally 2 h later. Then the mice were weighed daily and sacrificed on 14 d after infection. The bacterial load and pathological changes in lung were analyzed. Flow cytometry was performed to detect the proportions and numbers of neutrophils (CD45 + CD11b + Gr-1 high) and alveolar macrophages (CD45 + F4/80 + CD11c high)as well as the proportions of Th1 (IFN-γ + CD4 + ) and Th2 (IL-4 + CD4 + ) cells. ELISA was also performed to measure IFN-γ and IL-4 levels in spleen cell culture supernatants. Results:Compared with WT mice, IL-21R -/- mice showed elevated numbers and enhanced activation of CD4 + T cells, increased proportion of Th1 cells and decreased proportion of Th2 cells in spleen and lung tissues after Cm respiratory infection. Besides, IFN-γ levels increased, while IL-4 levels decreased in spleen cell culture supernatants of IL-21R -/- mice. After Cm infection, the na?ve WT transferred with CD4 + T cells from IL-21R -/- mice showed less body weight loss, reduced bacterial load and alleviated pathological changes in lung tissues, increased proportion of Th1 cells in lung tissue and higher IFN-γ level in spleen cell culture supernatants. Conclusions:IL-21/IL-21R-mediated CD4 + T cells could aggravate Cm respiratory infection by suppressing Th1 cell immune responses.