A novel therapeutic approach to modulate the inflammatory cascade: A timely exogenous local inflammatory response attenuates the sepsis-induced cytokine storm.

BACKGROUND: The emergence of severe sepsis is contingent upon the occurrence of a cytokine storm (CS), a multifaceted process intricately entwined with the temporal dimension, thereby rendering the infection response remarkably intricate. Consequently, it becomes imperative to discern and accurately identify the optimal timing for interventions, predicated upon the dynamic timeline of inflammatory changes. Moreover, the administration of exogenous low-dose pro-inflammatory agents has exhibited the potential to impede the relentless progression of the inflammatory cascade. Hence, the present study aims to scrutinize the impact of exogenous Local Inflammatory Response (eLIR) on the body surface in the context of the inflammatory cascade during sepsis, within a temporal framework, with a particular emphasis on the point of exacerbation of inflammation. METHODS: Rats were induced sterile sepsis by intraperitoneal injection of zymosan (ZY) at an appropriate dosage. The temporal progression of inflammatory changes and eLIR effects were described based on the trend of serum crucial inflammatory cytokines, tring to quest time-point of inflammatory aggravation in sepsis. Then, the varying degrees of surface inflammation caused by eLIR on this time point leading to the final effects on the inflammatory cascade response were explored. In addition, given the authentic pathological progression of sepsis, further observation was conducted on the impact of another intervention timing of eLIR on the inflammatory cascade. The survival rate was measured. Serum and organ related inflammatory cytokines were detected, and organ histopathology was investigated. RESULTS: In present study, a dosage of 600 mg/kg ZY was found to be optimal for the sterile sepsis model. Initiating eLIR 6 h prior to ZY injection, the maximum effect point of eLIR could be precisely align with the inflammatory aggravation point of sterile sepsis. Initiating eLIR at this time, 3 sessions of eLIR were found to be more effective than 1 or 2 sessions in mitigating inflammatory responses during the initial stage of inflammation and the peak of inflammation. Notably, the findings also suggested that this intervention improve survival rate. In addition, the anti-inflammatory efficacy has been substantially diminished by the prompt initiation of 3 sessions of eLIR immediately after ZY injection at the onset of sepsis. Similarly, the current findings did not demonstrate a statistically significant enhancement in survival rates with eLIR at this time point. CONCLUSIONS: Compared with the initial stage of inflammation, low-scale inflammation caused by a certain intensity of eLIR (3 sessions) on the body surface can more effectively pry the inflammation aggravation time-point, thereby shifting the pro-inflammatory to anti-inflammatory milieu, impeding the disproportionate cytokines release in inflammatory diseases, slowing down the inflammatory cascade, and improving the survival rate of sepsis.

Rethinking about acupuncture intervention opportunity based on dynamic perspective of inflammatory response. / åŸºäºŽç‚Žæ€§ååº”åŠ¨æ€æ€§è§†åŸŸä¸‹å¯¹é’ˆç¸ä»‹å ¥æ—¶æœºçš„å†æ€è€ƒ.

Acupuncture and moxibustion therapies are widely used in the field of anti-inflammation, but the dynamic characteristics of inflammatory response with time in the modern biological mechanism research has been ignored to some extent. Therefore, the body surface intervention system represented by acupuncture-moxibustion urgently needs to rebuild the research perspective oriented to the complex immune regulation model, and then to explore the opportunity of acupuncture-moxibustion anti-inflammatory intervention according to the dynamic change process of inflammatory response. Through comparative analysis on the ancient and modern acupuncture-moxibustion immune regulation, and starting from the construction of clinical body surface intervention system, we propose that grasping the appropriate "intervention opportunity" is an important entry point that cannot be ignored to effectively "pry" inflammatory response.

[Effect on expression of vascular smooth muscle cell calcium channel in rats exposed in low temperature].

OBJECTIVE: To observe the expression of vascular smooth muscle cells calcium channel α1C subunit (LTCCα1C) in rats exposed in low temperature. METHODS: Cold-induced hypertension was established and blood pressure was measured every two weeks. The mRNA expression of L type calcium channel α1C was determined by RT-PCR. RESULTS: The blood pressure of the rats exposed to cold environment increased. The blood pressure of experimental groups [(102.8 ± 2.25) mm Hg] began to increase from the first two weeks, compared with the control group [(89.2 ± 3.73) mm Hg], there were significant difference (P < 0.05). The blood pressure of experimental groups were (114.5 ± 4.21), (121.9 ± 3.03) mm Hg respectively at 4, 6 weeks. Compared with the control group, the expression of LTCCα1C mRNA of the cold exposure group increased significantly (P < 0.01). There was a significant correlation between the expression of LTCCα1C mRNA and the blood pressure of the rats (r = 0.86, P < 0.01). CONCLUSION: Repeated cold exposure can establish cold-induced hypertension, and the level of vascular smooth muscle cells LTCCα1C expression increase.

[Cardiovascular circulation feedback control treatment instrument].

The cardiovascular circulation feedback control treatment instrument (CFCTI) is an automatic feedback control treatment system, which has the function of monitoring, alarming, trouble self-diagnosis and testing on the line in the closed loop. The instrument is designed based on the successful clinical experiences and the data are inputted into the computer in real-time through a pressure sensor and A/D card. User interface window is set up for the doctor's choosing different medicine. The orders are outputted to control the dose of medicine through the transfusion system. The response to medicine is updated continually. CFCTI can avoid the man-made errors and the long interval of sampling. Its reliability and accuracy in rescuing the critical patients are much higher than the traditional methods.