OBJECTIVE: To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms. METHODS: Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy. RESULTS: Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD₈⁺ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD₄⁺ T subset and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD₄⁺ T subset, and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged. CONCLUSION Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals ; Irritable Bowel Syndrome/immunology* ; Rats ; Moxibustion ; Intestinal Mucosa/immunology* ; Female ; Diarrhea/therapy* ; Intestine, Small/immunology* ; Male ; Humans ; Rats, Sprague-Dawley ; Disease Models, Animal

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Lactic acid (LA) accumulation in tumor microenvironments (TME) has been implicated in immune suppression and tumor progress. Diverse roles of LA have been elucidated, including microenvironmental pH regulation, signal transduction, post-translational modification, and metabolic remodeling. This review summarizes LA functions within TME, focusing on the effects on tumor cells, immune cells, and stromal cells. Reducing LA levels is a potential strategy to attack cancer, which inevitably affects the physiological functions of normal tissues. Alternatively, transporting LA into the mitochondria as an energy source for immune cells is intriguing. We underscore the significance of LA in both tumor biology and immunology, proposing the burning of LA as a potential therapeutic approach to enhance antitumor immune responses.
Humans ; Tumor Microenvironment/immunology* ; Neoplasms/therapy* ; Lactic Acid/immunology* ; Mitochondria/metabolism* ; Animals ; Signal Transduction

Objective To construct an assay for early infection diagnosis of Angiostrongylus cantonensis based on gold nanorod polymerization.Methods Stable gold nanorods were synthesized by the gold seed growth method,and labeled with different concentrations of sulfhydrylated crude and purified antigens of lar-vae and adults of Angiostrongylus cantonensis,and their excretory and secretory antigens,and then scanned the longitudinal surface plasmon resonance(LSPR)of the stable gold nanorods by ultraviolet-visible(UV-Vis)spectrophotometry,and screened for the optimal labeled antigens for the detection of different infection time after infection of rats with Angiostrongylus cantonensis.The displacement changes were screened to se-lect the best labeled antigens for the detection of serum antibodies and positive sera of series of dilution gradi-ents at different infection times(5,7,14,21 d)after infection with Angiostrongylus cantonensis in rats,and at the same time,the enzyme-linked immunosorbent assay(ELISA)was set up for the same test.Kappa test was used to compare the consistency of the two assays.Results Gold nanorods with stable aspect ratio were suc-cessfully prepared.The gold nanorods labeled with 10 μg/mL of adult purified antigen had a maximum LSPR shift of 40 nm,and were able to detect serum antibodies in rats 5 d after mild,moderate and severe infection with Angiostrongylus cantonensis,as well as positive sera at a maximum dilution of 1∶600.The ELISA was able to detect serum antibodies in rats after 14 d of mild infection,and 7 d of moderate and severe infection,as well as positive sera at a maximum dilution of 1∶200.The ELISA detected positive serum antibodies in rats after 14 d of mild infection and 7 d of moderate and severe infection,as well as in rats at a maximum dilution of 1∶200.The Kappa value of the two methods was 0.750(P<0.01),and the results of the two methods had strong consistency.Conclusion A polymerized gold nanorod assay for early and rapid diagnosis of An-giostrongylus cantonensis infection is successfully constructed.

Microorganisms are an indispensable part of nature,they play an important role in the material cycle.With the continuous development of microbial genomics research,we have a deeper understanding of the uncultured microorganisms:the current culture of microorganisms accounted for less than 3%of the total number of natural microorganisms,even 0.5%.The low cultivability of microorganisms is still a major obstacle to microbial research and application.In recent years,the world for the uncultured microorganisms,continuous research,in situ culture technology,high throughput separation culture and other new methods.But at present,these new methods still exist in the cultivation of microorganisms are not comprehensive,for the abundance of the requirements and other shortcomings,need to continue to practice and improvement.This paper for the necessity of pure culture of microorganisms,the importance of the nearly 30 years of global pure culture of microorganisms,the current research shortcomings and future research directions have been made a preliminary summary and analysis.

Objective·To verify the accuracy and clinical feasibility of fluoroscopic stereophotogrammetric analysis(FSA)technology based on two dimension(2D)-three dimension(3D)registration for early migration detection of aseptic loosening of joint prostheses.Methods·2D-3D registration algorithms centering on the light source and projected object respectively in FSA technology were verified under various working conditions through image synthesis experiments,and the feasibility of clinical application was verified through real model experiments.The image synthesis experiment established a perspective projection environment with the same parameters as the real environment in a virtual environment,the 2D perspective images of the 3D model(bone or prosthesis)during the six degrees of freedom transformation were recorded,and the six degrees of freedom transformation of the 3D model was restored by using different 2D-3D registration algorithms.The error of each registration algorithm was calculated.For real model validation,the migration between bone and prosthesis after joint replacement surgery was simulated with a high precision bone prosthesis migration simulator.The 3D model of the bone or prosthesis was reconstructed by using computed tomograph(CT)images and optical scanning,and the 2D perspective images before and after prosthesis migration were captured by using a fluoroscopy device.The migration of the prosthesis was restored by using FSA technology based on 2D-3D registration,and the error of FSA technology was calculated.Results·The accuracy of the 2D-3D registration algorithm centering on the light source was higher than that of the algorithm centering on the projected object under different working conditions.When the initial registration conditions were favorable,the algorithm centering on the light source reduced the rotation error compared to the algorithm centering on the projected object,with a statistical difference(P=0.021),and the displacement error decreases,with a significant statistical difference(P=0.000).Moreover,algorithms centering on the light sources required lower similarity and fewer registration times to meet clinical application requirements.Conclusion·The accuracy of FSA technology based on 2D-3D registration in early migration detection of artificial joint prostheses meets clinical application requirements.This technology can warn of late aseptic loosening of prostheses by detecting early migration of prostheses after joint replacement surgery,and is expected to be applied to clinical practice through further research.