Intestinal tuberculosis (ITB) is a specific infection caused by Mycobacterium tuberculosis invading the intestinal wall, encompassing two types: primary and secondary. In clinical practice, it is more commonly secondary to extrapulmonary tuberculosis, such as cavitary pulmonary tuberculosis. In recent years, the incidence of ITB has shown an increasing trend. Due to its insidious onset and the lack of obvious or specific early symptoms, early diagnosis is challenging, often leading to a prolonged disease course. Therefore, accurate early diagnosis is of great significance for the control and prevention of ITB. Currently, the primary diagnostic methods for tuberculosis include etiological examination, histopathological evaluation, molecular biological diagnosis, and imaging studies. This article summarizes recent advances in the application of these diagnostic techniques for ITB, aiming to provide valuable insights for healthcare professionals.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Hormesis effect has been observed in the secondary metabolite synthesis of microorganisms induced by rare earth elements. However, the underlying molecular mechanism remains unclear. To analyze the molecular mechanism of the regulatory effect of Rhodotorula mucilaginosa in the presence of lanthanum chloride, different concentrations of lanthanum chloride were added to the fermentation medium of Rhodotorula mucilaginosa, and the carotenoid content was subsequently measured. It was found that the concentrations of La³⁺ exerting the promotional and inhibitory effects were 0-100 mg/L and 100-400 mg/L, respectively. Furthermore, the expression of 33 genes and the synthesis of 55 metabolites were observed to be up-regulated, while the expression of 85 genes and the synthesis of 123 metabolites were found to be down-regulated at the concentration range of the promotional effect. Notably, the expression of carotenoid synthesis-related genes except AL1 was up-regulated. Additionally, the content of β-carotene, lycopene, and astaxanthin demonstrated increases of 10.74%, 5.02%, and 3.22%, respectively. The expression of 5 genes and the synthesis of 91 metabolites were up-regulated, while the expression of 35 genes and the synthesis of 138 metabolites were down-regulated at the concentration range of the inhibitory effect. Meanwhile, the content of β-carotene, lycopene, and astaxanthin decreased by 21.73%, 34.81%, and 35.51%, respectively. In summary, appropriate concentrations of rare earth ions can regulate the synthesis of secondary metabolites by modulating the activities of various enzymes involved in metabolic pathways, thereby exerting the hormesis effect. The findings of this study not only contribute to our comprehension for the mechanism of rare earth elements in organisms but also offer a promising avenue for the utilization of rare earth elements in diverse fields, including agriculture, pharmaceuticals, and healthcare.
Lanthanum/pharmacology* ; Rhodotorula/genetics* ; Carotenoids/metabolism* ; Hormesis/drug effects* ; Fermentation ; Multiomics

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

Objective:To examine the efficacy and safety of third-party bone marrow-derived mesenchymal stem cells (MSCs) in the treatment of refractory delayed hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Twenty patients with refractory LOHC received conventional therapy combined with MSCs obtained from third-party donors’ bone marrow (BM) . MSCs were given intravenously at a dose of 1 × 10 6 cells/kg once weekly until either the symptoms improved or no changes in LOHC were seen after continuous infusion four times. BK viruria (BKV) -DNA, JC viruria (JCV) -DNA, and CMV-DNA were detected by real-time quantitative PCR before and 8 weeks after the MSCs infusion. Results:① Of the 20 patients with refractory LOHC, 15 were males, and 5 were females, and the median age was 35 (15-56) years. There were 5 cases of acute lymphoblastic leukemia (ALL) , 9 cases of acute myeloid leukemia (AML) , 5 cases of myelodysplastic syndrome (MDS) , and 1 case of maternal plasma cell like dendritic cell tumor (BPDCN) . There were 4 cases of HLA identical transplantation and 16 cases of HLA incomplete transplantation. ②The median number of MSC infusions for each patient was 3 (range: 2-8) . Seventeen patients achieved complete response, and one had a partial response after treatment. The overall response rate was 90%. Over a median follow-up period of 397.5 days (range 39-937 days) post-transplantations, 13 patients survived, and 7 died. The causes of death included aGVHD (1 case) , infections (5 cases) , and TMA (1 case) . ③The copy numbers of BKV-DNA and CMV-DNA in urine in the 8th week after MSCs infusion were significantly lower than those observed before treatment (11342.1×10 8 copies/L vs 5.2×10 8 copies/L, P=0.016; 3170.0×10 4 copies/L vs 0.2×10 4 copies/L, P=0.006, respectively) , while JCV-DNA did not significantly differ when compared to before treatment ( P=0.106) . ④ No adverse reactions related to MSC infusion occurred in any of the 20 patients. Conclusion:Third-party bone marrow-derived MSC has significant efficacy and good safety in the treatment of refractory LOHC after allogeneic HSCT.

Objective To explore the diagnostic value of CD4 cell count and IL-6/IL-10 ratio in combination for the diagnosis of AIDS complicated with Pneumocystis pneumonia. Methods A total of 100 AIDS patients with pneumocystis pneumonia admitted to the Nanchong Central Hospital from January 2018 to May 2019 were enrolled in the AIDS pneumonia group, 100 AIDS patients were enrolled in the AIDS group, and 100 healthy subjects were included in the control group. The number of CD4+T cells in serum was detected by flow cytometry, and the expression levels of IL-6 and IL-10 in serum were detected by enzyme-linked immunosorbent assay. The AUC of receiver operating characteristic curve (ROC) was used to analyze the CD4 cell count and the diagnostic significance of IL-6/IL-10 detection in AIDS with pneumocystis pneumonia. Results The number of CD4 cells in the serum of AIDS patients with Pneumocystis pneumonia was significantly lower than that of AIDS patients and healthy subjects (t=28.31, P<0.0001; t=36.90, P<0.0001), but the ratio of IL-6/IL-10 was higher than that of AIDS patients and healthy individuals (t=7.184, P<0.0001; t=19.03, P<0.0001). The sensitivity of CD4 cell count and IL-6/IL-10 ratio in the diagnosis of AIDS patients with Pneumocystis pneumonia was 92.00%, the specificity was 88.00%, and the accuracy was 89.33%. Conclusion The detection of CD4 cell count and IL-6/IL-10 ratio can be used as a potential marker for the diagnosis of AIDS with Pneumocystis pneumonia.

Objective To explore the effects of the new melatonin nonselective agonists Neu-P11 on intraocular pressure (IOP) and glial fibrillary acid protein (GFAP) expression in the retina of acute high IOP rat.Methods Twenty-four male Sprague-Dawley rats were randomly divided into 4 groups (6 cases in each group):Normal IOP with local treatment (NIL) group,high IOP with local treatment (HIL) group,HILwith melatonin treatment (HIL-M) group,HIL with Neu-P11 treatment (HIL-N) group.10 μL normal saline was instilled in NIL group and HIL group,while 10 μL 100 μmol · L-1 Mel/Neu-P11 treated in HIL-M group and HIL-N group.After 2 hours of rest,rats were placed in the Trendelenburg position duration 45 minutes.And then,IOP was measured every hour for 6 hours,and repeated it for a week.The excessive sodium pentobarbital was injected to SD rats at the end of the experiment.The rat eyeballs were took out to perform HE and immunohistochemical staining to detect retina GFAP protein expression.Results After a week,IOP in HIL group was (41.26 ± 1.73) mmHg (1 kPa =7.5 mmHg),NIL group was (13.61 ± 0.55) mmHg,which mean the Trendelenburg could induce high IOP in SD rats.Compared with the NIL group,the retinal becoming thick,the level of organization was not clear and the expression of GFAP protein was quite high in HIL group.At the same time,the GFAP protein expression and IOP were significantly weakened in HIL-M group and HIL-N group compared with HIL group.Conclusion Neu-P1 1 can reduce IOP,inhibit the activation of gliocyte,and decrease the expression of GFAP to protect the retina.