Association between intracellular adenosine triphosphate content of CD4+ T lymphocytes and mortality in sepsis patients: A prospective observational study.

OBJECTIVE: This study aimed to link intracellular adenosine triphosphate content in CD4+ T lymphocytes (CD4+ iATP) with sepsis patient mortality, seeking a new predictive biomarker for outcomes and enhanced management. METHODS: 61 sepsis patients admitted to the Intensive Care Unit between October 2021 and November 2022 were enrolled. iATP levels were gauged using whole blood CD4+ T cells stimulated with mitogen PHA-L. Based on CD4+ iATP levels (<132.24 and ≥132.24 ng/mL), patients were categorized into two groups. The primary endpoint was all-cause mortality. To identify factors associated with mortality, both univariate and multivariate Cox proportional hazard analyses were conducted. RESULTS: Of the patients, 40 had high CD4+ iATP levels (≥132.24 ng/mL) and 21 had low levels (<132.24 ng/mL). In a 28-day follow-up, 21 (34.4%) patients perished. Adjusting for confounders like SOFA score, APACHE II score, lactic acid, and albumin, those with low CD4+ iATP had three- to fivefold higher mortality risk compared to high CD4+ iATP patients (61.9% vs. 20.0%; hazard ratio [95% confidence interval], Model 1: 4.515 [1.276-15.974], p = .019, Model 2: 3.512 [1.197-10.306], p = .022). CD4+ iATP correlated positively with white blood cell and neutrophil counts but not with lymphocytes, CD3, and CD4 counts. CONCLUSIONS: Low CD4+ iATP levels were associated with a higher risk of mortality in sepsis patients. Measurement of CD4+ iATP may serve as a useful tool for identifying patients at a higher risk of mortality and could potentially provide a basis for clinical treatment. Further research is warranted to fully elucidate the underlying mechanisms of this association.

The transplant rejection response involves neutrophil and macrophage adhesion-mediated trogocytosis and is regulated by NFATc3.

The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.

Nitric oxide-induced endoplasmic reticulum stress of Schistosoma japonicum inhibits the worm development in rats.

Schistosomiasis, caused by Schistosoma spp., is a zoonotic parasitic disease affecting human health. Rattus norvegicus (rats) are a non-permissive host of Schistosoma, in which the worms cannot mature and cause typical egg granuloma. We previously demonstrated that inherent high levels of nitric oxide (NO), produced by inducible NO synthase (iNOS), is a key molecule in blocking the development of S. japonicum in rats. To further explore the mechanism of NO inhibiting S. japonicum development in rats, we performed S-nitrosocysteine proteomics of S. japonicum collected from infected rats and mice. The results suggested that S. japonicum in rats may have undergone endoplasmic reticulum (ER) stress. Interestingly, we found that the ER of S. japonicum in rats showed marked damage, while the ER of the worm in iNOS-/- rats and mice were relatively normal. Moreover, the expression of ER stress markers in S. japonicum from WT rats was significantly increased, compared with S. japonicum from iNOS-/- rats and mice. Using the NO donor sodium nitroprusside in vitro, we demonstrated that NO could induce ER stress in S. japonicum in a dose-dependent manner, and the NO-induced ER stress in S. japonicum could be inhibited by ER stress inhibitor 4-Phenyl butyric acid. We further verified that inhibiting ER stress of S. japonicum in rats promoted parasite development and survival. Furthermore, we demonstrated that NO-induced ER stress of S. japonicum was related to the efflux of Ca2+ from ER and the impairment of mitochondrial function. Collectively, these findings show that high levels of NO in rats could induce ER stress in S. japonicum by promoting the efflux of Ca2+ from ER and damaging the mitochondrial function, which block the worm development. Thus, this study further clarifies the mechanism of anti-schistosome in rats and provides potential strategies for drug development against schistosomiasis and other parasitosis.

Analysis of spatial-temporal pattern, dynamic evolution and influencing factors of health tourism development in China.

The evaluation index system is constructed based on the connotation and characteristics of health tourism. Using the entropy method, Thiel index, exploratory spatial data analysis method, spatial Markov chain and spatial econometric model, research is carried out around the development index, difference status, spatial-temporal pattern, dynamic evolution and influencing factors of health tourism. The following results were drawn: (1) The development index of health tourism in China is low, but the development speed is fast. The inter-regional development index shows an eastern China > central China > western China pattern, and the development speed exhibits a western China > central China > eastern China situation. (2) In the overall difference in China's health tourism development, the intra-regional difference is consistently higher than the inter-regional difference. Among the three major regions, the overall difference between eastern China and western China is always higher than that of central China. (3) The development of health tourism in China is positively correlated in the global space, with some local spatial clustering. (4) The dynamic evolution of health tourism development in China shows part of the "Matthew effect" characteristics, with an obvious spatial spillover effect. (5) Various influencing factors produced widely varying direct, indirect and total effects on health tourism development in China, eastern China, central China and western China. Finally, based on the results of the above empirical analysis, policy recommendations to promote the development of health tourism in China are proposed.