To investigate the clearance capacity of cardiac resident macrophages in post-sepsis and its underlying mechanism.

A mouse model of sepsis was established using cecum perforation ligation. Thirty male C57BL/6 mice (8 weeks old, weighing 20~25 g) were randomly and equally divided into a sham operation group (sham group) and a model group (sepsis group). Immunofluorescence assay was employed to label the cardiomyocytes and macrophages to observe the apoptosis of cardiomyocytes and the phagocytosis by cardiac resident macrophages. Cardiac resident macrophages were extracted for transcriptomic sequencing to determine the functional changes of the cells after sepsis. Cardiac resident macrophage cell lines were established at the cellular level and served as the normal group (RAC group), and the RAC cells treated with LPS were subjected as the sepsis group (RAC+LPS group). Then the differences in the ability to clear apoptotic cardiomyocytes between the 2 groups were observed. Then DQ-BSA-RED lysosomal activity detection probe, Lyso-Sensor yellow/bule dye, ELISA, and Western blotting were applied to detect the lysosomal function of cardiac resident macrophages, activity and expression of important lysosomal hydrolases, changes in contents and related subunits of vacuolar-type adenosine triphosphatases (V-ATPase).

Compared with the sham group, the sepsis group had larger number of apoptotic cardiomyocytes (P < 0.05) and increased phagocytosis of cardiomyocytes by cardiac macrophages (P < 0.05). The results of transcriptomic sequencing revealed a significant dysfunction of lysosome-associated functions of cardiac-resident macrophages after sepsis. In in vitro experiments, the RAC+LPS group had a reduced fragmentation capacity of apoptotic cardiomyocytes, reduction in the intensity of yellow fluorescence of lysosomes (P < 0.05), and decrease in lysosomal hydrolase activity (P < 0.05) when compared with the RAC group. In addition, LPS treatment significantly decreased the activity and expression of V-ATPase and its major subunit ATP6V1A in cardiac resident macrophages (P < 0.05).

Cardiac resident macrophages show reduced clearance of apoptotic cardiomyocytes after sepsis, which may be related to a decrease in the activity of ATP6V1A, an important subunit of its lysosomal V-ATPase, and reduced activity of lysosomal hydrolases.

To investigate the protective effect of dexmedetomidine on pulmonary edema in rats with hemorrhagic shock after exposure to a plateau environment.

A total of 280 SD male rats（10 weeks old, 200~220 g）were randomly divided into 4 groups: the plateau control（sham）group, the hemorrhagic shock after exposure to the plateau environment（HS）group, the lactated Ringer's resuscitation（LR）group, and the dexmedetomidine + lactated Ringer's resuscitation（DEX+LR）group. Using a low-pressure hypoxic chamber to simulate 5 000 m altitude, the rats have stayed the chamber for 48 h to accept pretreatment, injecting oleic acid treatment via the tail vein. After 0.5 h of induction of oleic acid, the rats were slowly drawn blood via the femoral artery（40% to 50% of the blood volume）to establish a model of hemorrhagic shock after exposure to the plateau environment. The effect of dexmedetomidine on pulmonary vascular permeability was observed by changes in lung water content, pulmonary microvascular permeability and alveolar lavage fluid protein concentration after prophylactic administration of dexmedetomidine; The effect of dexmedetomidine on respiratory function was observed by measuring respiratory rate and tidal volume; Pathological changes of lung tissue was detected by HE staining; Blood gas analysis was used to detect the effect of dexmedetomidine on arterial blood gases and survival rate.

Compared with the sham group, the lung water content, pulmonary microvascular permeability and alveolar lavage fluid protein concentration of the rats in the HS group increased（P<0.05）. The respiratory rate increased（P<0.05）, and the tidal volume and minute ventilation decreased（P<0.05）. Results of HE staining showed that the alveolar wall was thickened, and the lumen of alveoli was partially narrowed, with infiltration of inflammatory cells. Results of arterial blood gas suggested there was acidosis, and rats were in a hypoxic state（P<0.05）. Compared with the HS group, the rats in the LR group had aggravated pulmonary oedema. HE staining showed there was a fusion of alveolar sacs, lung tissue structure was destroyed and appeared obvious inflammatory cell infiltration. Respiratory rate and tidal volume increased, and arterial blood gas got deteriorated（P<0.05）. Dexmedetomidine significantly improved the lung function of rats with hemorrhagic shock pulmonary oedema after exposure to the plateau environment, and there was a decreased in pulmonary microvascular permeability, lung water content and alveolar lavage fluid protein concentration, compared with the lactated Ringer's solution resuscitation group（P<0.05）. The tidal volume, respiratory rate and minute ventilation of the rats tended to be higher than that of the plateau control group（P<0.05）. HE staining results showed that the alveolar structure tended to be intact, and the exudation in the alveolar lumen was reduced or even disappeared. Arterial blood gas analysis suggested that the level of acidosis was improved（P<0.05）, which eventually improved the survival rate.

Pulmonary edema is more likely to be induced during the resuscitation of rats with hemorrhagic shock after exposure to the plateau environment, and prophylactic administration of dexmedetomidine（10 μg/kg）is effective in preventing the development of pulmonary oedema.

To investigate the effect and mechanism of propofol on myocardial systolic dysfunction in sepsis.

Cecal ligation and puncture（CLP）was used to induce a septic rat model. Twenty-four adult SD rats were randomly divided into sham group, sepsis group（the samples were taken 12 h after CLP modeling）and propofol group（10 mg/kg propofol was injected intraperitoneally in 0 and 12 h after CLP modeling, and the samples were taken 3 h after the second injection of propofol）. Sarcomere length and intracellular calcium fluorescence intensity of myocardial cells were measured by cell microtensiometer. Further, acute isolated cardiomyocytes from the propofol group were incubated with inositol 1,4,5-triphosphate receptor（IP₃R）inhibitor 2-aminoethyl diphenylborinate（2-APB）, sarco/endoplasmic reticulum Ca²⁺-ATPase（SERCA）inhibitor 2, 5-di-t-butyl-1, 4-benzohydroquinone（BHQ）, ryanodine receptor（RyRs）inhibitor azumolene, and large conductance calcium-activated potassium channel（BKCa）inhibitor paxiline, respectively. Then sarcomere length and intracellular calcium fluorescence intensity of myocardial cells were measured again.

Compared with the sham group, the contractile function and calcium transient amplitude of myocardial cells were significantly decreased in the sepsis group, while propofol treatment obviously restored the contractile function and calcium release ability of myocardial cells in sepsis, with a maximum contractile amplitude restoration of 27.6%（P<0.05）and a maximum calcium transient amplitude restoration of 41.2%（P<0.05）. However, 2-APB and BHQ notably suppressed the improvement of contractile function of cardiomyocytes induced by propofol, with an inhibitory rate of 62.61%（P<0.05）and 42.15%（P<0.05）, respectively. However, azumolene had no significant effect on contractile function. Further studies showed that azumolene, 2-APB and BHQ had inhibitory effects on calcium transients with different extent. Among the 3 inhibitors, azumolene showed the mildest inhibitory effect, with a rate of 46.94%（P<0.05）, and the rate was 65.28%（P<0.05）and 65.33%（P<0.05）, respectively for 2-APB and BHQ. Paxiline had no statistical effect on propofol improving myocardial contractile function and calcium transients.

Propofol improves the contractile function of myocardial cells in sepsis, which may be related to the regulation of calcium concentration through IP₃R and SERCA.

To investigate the protective mechanism of dexmedetomidine（Dex）on early postoperative cognitive function in the elderly by determining cognitive function-related metabolites during the early postoperative period following intervention.

A randomized, single-blind, placebo-controlled study was conducted on 48 elderly patients undergoing joint replacement surgery（including hip and knee replacement surgeries）due to arthritis in Army medical center from January to May 2022. They were 10 males and 38 females, at an average age of 71.38（ranging from 65 to 89）years. They were randomly divided into a Dex group（n=32）and a control group（CON group, receiving 0.9% saline at an equal rate and volume via same way, n=16）in a ratio of 2∶1. Mini-Mental State Examination（MMSE）was performed to evaluate cognitive function before and 1 d after the surgery. Metabolomic analysis was carried out on the serum samples harvested on the day of surgery and 1 d after using ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry（UHPLC-QE-MS）in order to screen for differential metabolites and their pathways.

Postoperative cognitive dysfunction（POCD）was defined as a decrease in MMSE score by ≥2 points when compared to the preoperative score. The incidence of POCD was 6.25% and 37.5%, respectively, in the Dex group and CON group, with statistical significance（Chi-square=5.419, P=0.02）. Metabolomics analysis revealed 70 differential metabolites, including significantly down-regulated compounds such as ethyl dodecanote, prostaglandin D2, Indoxyl sulfate, Epibrassinolide, Diacylglycerol（18∶4/15∶0/0∶0）, Ganoderide H. Up-regulated metabolites included, L-Alloisoleucine, L-Norleucine, Betaine, 3,3,5-triiodo-L-thyronine-beta-D-glucuronoside, Phosphatidylcholine（22∶6/16∶1）, Phosphatidylcholine（22∶5/14∶0）, Phosphatidylcholine（18∶4/18∶1）, Cephalin（20∶3/14∶1）, Glycerophosphocholine, L-Serine, Gamma-Aminobutyric acid. The main pathways involved were glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, and pathways related to glycine, serine, and threonine metabolism, as well as pathways related to alanine, aspartate, and glutamate metabolism.

Dex protects early postoperative cognitive function by participating in various biological pathways such as lipid metabolism, amino acid metabolism, suppressing inflammatory reactions, alleviating oxidative stress, improving synaptic structure and function, and regulating cellular energy metabolism.

To investigate the protective effects of sterofundin on myocardial injury in septic rats.

A total of 280 SPF SD rats (half male and female, 12~14 weeks old, 200~220 g) were randomly divided into 4 groups: sham operation (Sham) group, sepsis (Sep) group, conventional treatment (Ct) group (with Ringer's lactate solution+dopamine+cefuroxime sodium), and malate ringer's solution (Mr) group (with sterofundin+dopamine+cefuroxime sodium). The rat model of sepsis was inflicted by cecal ligation and puncture (CLP). Subsequently, the effects of sterofundin treatment on the myocardial injury, cardiac output (CO), oxygen supply and consumption, liver and kidney perfusion, liver and kidney functions, survival time and survival rate of septic rats were observed.

The cardiac output (CO), cardiac index (CI) and stroke index (SI) were significantly decreased in the Sep group, while the injuries were improved to some extent in the Ct group (P<0.05). As compared with the Sep group, the improvement was more obvious in the Mr group, with CO, CI and SI values increased by 48.9%, 52.9% and 21.7% respectively, and the values were also greatly higher than those in the Ct group (P<0.05). The mean arterial blood pressure was remarkably declined to about 70 mmHg in the Sep group, slightly improved to around 90 mmHg in the Ct group, and notably elevated in the Mr group by 43.2% when compared with the Sep group (P<0.05). In addition, the liver and kidney functions were significantly ameliorated in the Mr group, along with decreased troponin T and lactate dehydrogenase, enhanced oxygen supply and consumption, alleviated myocardial interstitial edema and less myocardial fiber breakage, which greatly improved the survival rate of animals (P<0.05).

Sterofundin obviously improves the heart function and thus plays a protective role in organ functions in septic rats.