Aprepitant attenuates NLRC4-dependent neuronal pyroptosis via NK1R/PKCδ pathway in a mouse model of intracerebral hemorrhage.

BACKGROUND: Pyroptosis is a programmed cell death mediated by inflammasomes. Previous studies have reported that inhibition of neurokinin receptor 1 (NK1R) exerted neuroprotection in several neurological diseases. Herein, we have investigated the role of NK1R receptor inhibition using Aprepitant to attenuate NLRC4-dependent neuronal pyroptosis after intracerebral hemorrhage (ICH), as well as the underlying mechanism. METHODS: A total of 182 CD-1 mice were used. ICH was induced by injection of autologous blood into the right basal ganglia. Aprepitant, a selective antagonist of NK1R, was injected intraperitoneally at 1 h after ICH. To explore the underlying mechanism, NK1R agonist, GR73632, and protein kinase C delta (PKCδ) agonist, phorbol 12-myristate 13-acetate (PMA), were injected intracerebroventricularly at 1 h after ICH induction, and small interfering ribonucleic acid (siRNA) for NLRC4 was administered via intracerebroventricular injection at 48 h before ICH induction, respectively. Neurobehavioral tests, western blot, and immunofluorescence staining were performed. RESULTS: The expression of endogenous NK1R and NLRC 4 were gradually increased after ICH. NK1R was expressed on neurons. Aprepitant significantly improved the short- and long-term neurobehavioral deficits after ICH, which was accompanied with decreased neuronal pyroptosis, as well as decreased expression of NLRC4, Cleaved-caspase-1, GSDMD (gasdermin D), IL-1ß, and IL-18. Activation of NK1R or PKCδ abolished these neuroprotective effects of Aprepitant after ICH. Similarly, knocking down NLRC4 using siRNA produced similar neuroprotective effects. CONCLUSION: Aprepitant suppressed NLRC4-dependent neuronal pyroptosis and improved neurological function, possibly mediated by inhibition of NK1R/PKCδ signaling pathways after ICH. The NK1R may be a promising therapeutic target for the treatment of ICH.

Human herpesvirus 6B encephalitis in a liver transplant recipient: A case report and review of the literature.

Human herpesvirus 6B (HHV-6B) encephalitis in a liver transplant recipient is rarely reported. In this report, we presented a case of HHV-6B encephalitis in a liver transplant recipient and reviewed the relevant literature. A 56-year-old man was admitted to the intensive care unit (ICU) with an acute headache and intermittent convulsion 17 days after liver transplantation. Next-generation sequencing (NGS) of the cerebrospinal fluid (CSF) revealed 30691 sequence reads of HHV-6B and real-time polymerase chain reaction (real-time PCR) of the CSF detected HHV-6B DNA at 12 000 copies/mL, so the patient was diagnosed with HHV-6B encephalitis and received ganciclovir treatment promptly. The condition of the patient improved well and returned to the general ward with no neurologic deficits. This case indicated that adequate awareness, early diagnosis, and timely treatment are crucial to a good prognosis of HHV-6B encephalitis after liver transplantation.

Human encephalitis caused by pseudorabies virus infection: a case report.

Pseudorabies virus (PRV) primarily infects swine but can infect cattle, dogs, and cats. Several studies have reported that PRV can cross the specie barrier and induce human encephalitis, but a definitive diagnosis of human PRV encephalitis is debatable due to the lack of PRV DNA detection. Here, we report a case of human PRV encephalitis diagnosed by the next-generation sequencing (NGS) of PRV sequences in the cerebrospinal fluid (CSF) of a patient. A male pork vendor developed fever and seizures for 6 days. NGS results showed PRV sequences in his CSF and blood. Sanger sequencing showed that PRV DNA in the CSF and PRV antibodies in both the CSF and blood were positive. MRI results revealed multiple inflammatory lesions in the bilateral hemisphere. Based on the clinical and laboratory data, we diagnosed the patient with PRV encephalitis. This case suggests that PRV can infect humans, causing severe viral encephalitis. People at risk of PRV infection should improve their self-protection awareness.

Retrospective analysis of clinical features in 134 coronavirus disease 2019 cases.

We aimed to describe the clinical features in coronavirus disease 2019 (COVID-19) cases. We studied 134 critically ill COVID-19 cases from 30 December 2019 to 20 February 2020 in an intensive care unit (ICU) at Wuhan Jinyintan Hospital. Demographics, underlying diseases, therapy strategies and test results were collected and analysed from patients on admission, admission to the ICU and 48 h before death. The non-survivors were older (65.46 (s.d. 9.74) vs. 46.45 (s.d. 11.09)) and were more likely to have underlying diseases. The blood group distribution of the COVID-19 cases differed from that of the Han population in Wuhan, with type A being 43.85%; type B, 26.92%; type AB, 10% and type O, 19.23%. Non-survivors tend to develop more severe lymphopaenia, with higher C-reactive protein, interleukin-6, procalcitonin, D-dimer levels and gradually increased with time. The clinical manifestations were non-specific. Compared with survivors, non-survivors more likely to have organ function injury, and to receive mechanical ventilation, either invasively or noninvasively. Multiple organ failure and secondary bacterial infection in the later period is worthy of attention.

A modified PLASMIC score including the lactate dehydrogenase/the upper limit of normal ratio more accurately identifies Chinese thrombotic thrombocytopenic purpura patients than the original PLASMIC score.

BACKGROUND: The PLASMIC score was recently published to aid in the early identification of thrombotic thrombocytopenic purpura (TTP) patients. This study aims to evaluate whether this score is suitable for Chinese suspected TTP patients and find the utility of patients' other characteristics in predicting severe ADAMTS13 deficiency. METHODS: We retrospectively studied a Chinese cohort of 38 consecutive hospitalized patients with suspected TTP, ADAMTS13 test results, and other clinical data from September 2016 to May 2018. The predictive power of PLASMIC score in our cohort was evaluated, and patients' other characteristics, especially the high lactate dehydrogenase/the upper limit of normal (LDH/ULN), were studied to determine their distinguishing ability for TTP patients. RESULTS: In this Chinese cohort, 17 patients were diagnosed with TTP according to ADAMTS13 activity results. When dichotomized at intermediate-high risk (scores 5-7) vs low risk (scores 0-4), the PLASMIC score predicted TTP with a sensitivity of 100%, a specificity of 9.52%, and a misdiagnosis rate of 90.48%. And the LDH/ULN alone, or plus platelet count, reticulocyte percentage and indirect bilirubin (IBIL) both had excellent predictive power (area under the curve [AUC] 0.937, 95% confidence interval [CI] 0.863-1.000, P = .000, and AUC 0.994, 95% CI 0.980-1.000, P = .000, respectively). The model including platelet count, reticulocyte percentage, IBIL, and LDH/ULN ratio had a sensitivity of 100%, a specificity of 95.2%, and a misdiagnosis rate of 4.8%. CONCLUSIONS: A modified PLASMIC score plus LDH/ULN ratio might be more suitable for identifying ADAMTS13 deficiency patients, especially for making an earlier diagnosis, guiding the immediate and reasonable plasma exchange, and also avoiding unnecessary allocation of plasma.

Clinical Features and Prognostic Predictors in Patients with Renal Transplant Complicated by SARS-CoV-2 Infection, a Retrospective Single-Center Study.

Background: This study examines the clinical outcomes and prognostic factors of COVID-19 in renal transplant recipients. Given their immunosuppressed status, these patients are at higher risk of severe complications from COVID-19. The study aims to provide healthcare professionals with critical insights for diagnosing and managing this vulnerable population. Patients and methods: This retrospective cohort study included adult renal transplant recipients diagnosed with COVID-19. Data on demographics, medical history, laboratory results, and patient outcomes were analyzed to identify clinical characteristics and prognostic factors. Results: This study included 115 renal transplant recipients with COVID-19, predominantly male, with a mortality rate of 10.4% (12 deaths). The overall vaccination rate was 20%. Univariate analysis showed significant differences between survivors and non-survivors in initial serum creatinine levels, and percentages of neutrophils, monocytes, and lymphocytes, along with CRP levels on day 3. Additionally, CRP levels, hemoglobin, and platelet counts on day 7 also differed significantly. Multivariate analysis identified CRP levels on days 3 and 7, day 7 hemoglobin and platelet counts, and concurrent bacterial infections as independent risk factors for mortality. Conclusion: Elevated CRP levels, renal impairment, and bacterial co-infections play a significant role in the outcomes of COVID-19 in kidney transplant recipients. This study highlights the importance of monitoring these factors for early identification and management of high-risk patients.

Tetramethylpyrazine upregulates the aquaporin 8 expression of hepatocellular mitochondria in septic rats.

BACKGROUND: The sepsis-induced acute liver injury majorly depends on the dysfunction of mitochondria and the loss of cellular energy. Aquaporin 8 (AQP8) can modulate water transport and osmotic swelling of mitochondria in the inner mitochondrial membrane of the liver. In this study, we explore the effects of tetramethylpyrazine (TMP) on protecting the structure of hepatocyte mitochondria and modulating the expression of AQP8. MATERIALS AND METHODS: Forty-eight rats were randomly allocated to four groups: control group receiving sham procedure, septic group receiving cecal ligation and puncture (CLP), therapeutic group receiving 60 mg/kg of ligustrazine (TMP) intravenously from caudal vein immediately after CLP, and preventive group receiving 60 mg/kg/d of ligustrazine intravenously from caudal vein for 7 d before CLP. The mitochondrial ultrastructure of rat liver was observed. The protein expression of AQP8 was assayed by Western blot. Analysis of AQP8 messenger RNA (mRNA) expression level was performed by the reverse transcription-polymerase chain reaction. The mean fluorescence intensity (MFI) of rhodamine 123 (Rh 123) was measured by flow cytometry. The serum tumor necrosis factor alpha (TNF-α) level was determined by the enzyme-linked immunosorbent assay. RESULTS: The mitochondrial ultrastructure was markedly damaged in the septic group, whereas it was lightly damaged in the therapeutic and preventive groups. Compared with the control group, the AQP8 protein expression and MFI were significantly reduced, and the steady-state AQP8 mRNA and serum TNF-α levels were increased in the septic, therapeutic, and preventive groups. Compared with the septic group, the AQP8 protein expression and MFI were increased, and the steady-state AQP8 mRNA and serum TNF-α levels were decreased significantly in the therapeutic and preventive groups. There was no significant difference in morphologic characteristics, AQP8 protein level, AQP8 mRNA level, MFI, and serum TNF-α level between the therapeutic and the preventive groups. Linear positive correlation was observed between the AQP8 protein level and the MFI of Rh 123. Linear negative correlation was observed between the AQP8 protein level or the MFI of Rh 123 and serum TNF-α level. CONCLUSIONS: TMP has protective effect on hepatocellular mitochondria from damage in sepsis by ameliorating the expression of AQP8 protein in liver mitochondria. The protective effect of TMP on the liver mitochondria might not have a difference between using TMP before or after the occurrence of sepsis.

Activation of LRP6 with HLY78 Attenuates Oxidative Stress and Neuronal Apoptosis via GSK3ß/Sirt1/PGC-1α Pathway after ICH.

Background: Oxidative stress and neuronal apoptosis have important roles in the pathogenesis after intracerebral hemorrhage (ICH). Previous studies have reported that low-density lipoprotein receptor-related protein 6 (LRP6) exerts neuroprotection in several neurological diseases. Herein, we investigate the role of LRP6 receptor activation with HLY78 to attenuate oxidative stress and neuronal apoptosis after ICH, as well as the underlying mechanism. Methods: A total of 199 CD1 mice were used. ICH was induced via injection of autologous blood into the right basal ganglia. HLY78 was administered via intranasal injection at 1 h after ICH. To explore the underlying mechanism, LRP6 siRNA and selisistat, a Sirt1 selective antagonist, were injected intracerebroventricularly at 48 h before ICH induction. Neurobehavioral tests, Western blot, and immunofluorescence staining were performed. Results: The expression of endogenous p-LRP6 was gradually increased and expressed on neurons after ICH. HLY78 significantly improved the short- and long-term neurobehavioral deficits after ICH, which was accompanied with decreased oxidative stress and neuronal apoptosis, as well as increased expression of p-GSK3ß, Sirt1, and PGC-1α, as well as downregulation of Romo-1 and C-Caspase-3. LRP6 knockdown or Sirt1 inhibition abolished these effects of HLY78 after ICH. Conclusion: Our results suggest that administration of HLY78 attenuated oxidative stress, neuronal apoptosis, and neurobehavioral impairments through the LRP6/GSK3ß/Sirt1/PGC-1α signaling pathway after ICH.

Benzene poisoning presenting as status epilepticus: a case report and literature review.

Benzene is a common industrial chemical and an important environmental pollutant. In addition, exposure to benzene may cause injury to the nervous system, in vivo. However, few clinical cases of benzene-induced injury to the nervous system have been reported. Therefore, the present report highlights a case of benzene poisoning, presenting as status epilepticus. The patient was admitted to the intensive care unit (ICU) with a coma after experiencing seizures 7 hours ago. He had a history of exposure to paint containing benzene. In addition, cranial magnetic resonance imaging (MRI) revealed extensive bilateral signal abnormalities in the cerebral white matter. The level of the benzene metabolite was also high in the urine. Consequently, the patient was diagnosed with benzene poisoning and status epilepticus, after which he received nerve nourishment, enteral nutrition, mechanical ventilation, and other supportive measures. He regained normal consciousness and motor ability, 1 month after treatment. The patient was also followed-up for 15 months and it was shown that he had returned to normal life without neurological and psychological deficits. Moreover, cranial MRI showed that the lesions had disappeared. This case therefore indicated that benzene poisoning should be considered if the patient has a clear history of exposure to the chemical, presents with seizures and has extensive signal abnormalities in the white matter, revealed by MRI examination. Additionally, early diagnosis and effective supportive treatment can guarantee a favorable prognosis for benzene poisoning.

Fatal visceral disseminated varicella-zoster virus infection in a renal transplant recipient: A case report.

BACKGROUND: Visceral disseminated varicella-zoster virus (VZV) infection is a rare but life-threatening disease. In transplant recipients with VZV infection, visceral dissemination may develop without skin eruptions, which leads to the failure of early diagnosis. CASE SUMMARY: The patient was a 33-year-old male renal recipient who was referred to our hospital with severe upper abdominal pain of 3-d duration. On admission, the patient rapidly developed septic shock and multiple organ dysfunction syndrome with liver dysfunction and acute kidney injury. Next-generation sequencing of peripheral blood yielded 39224 sequence reads of VZV, and real-time polymerase chain reaction for VZV was positive, with 1.2 × 107 copies/mL. The final diagnosis was visceral disseminated VZV infection. Acyclovir and supportive therapy were started, but the patient died of severe visceral organ damage 16 h after admission. CONCLUSION: Visceral disseminated VZV infection is possible in renal transplant recipients presenting abdominal pain and rapidly-evolving organ damage without skin involvement.

Esophagitis dissecans superficialis associated with acute transoral paraquat poisoning: Clinical study of 15 cases.

To analyze the clinical characteristics and therapeutic effects of transoral paraquat poisoning combined with Esophagitis dissecans superficialis (EDS). A retrospective observational study was conducted on paraquat poisoning patients between January 1, 2011 and August 30, 2016 in Qilu hospital. Fifteen patients with EDS were enrolled in this study. The clinical characteristics, prognosis, and pathological features of esophageal necrosis mucosa of these patients were retrospectively analyzed and summarized. Esophageal mucosal dissection occurs mainly within 3-8 days after transoral paraquat poisoning in 15 patients. Dosage of paraquat is range from 50 to 100 ml. Most patients have physical problems with swallowing before the intramural esophageal dissection occurred. And there are other symptoms, including sore throat or dysphagia (100%), nausea and vomiting (86.7%), heartburn or upper abdominal pain (73.3%), hematemesis (60%), abdominal distension (20%) and cough frequently (6.7%). In death group, most patients demonstrate features of the multiple organ failure when the esophageal mucosal stripping happened, including lung injury, renal failure, and hepatic failure. The shape of esophageal dissection was tubular in 60%, irregular in 40%, and they vary in size. Pathological examination showed extensive injury, necrosis and hemorrhage of digestive tract epithelium, and obvious inflammatory reaction of epithelial tissue. Transoral paraquat poisoning has certain damage to the patient's esophageal mucosa, and some may be complicated with EDS, and the prognosis is poor, especially when combined with multiple organ dysfunction. Esophageal damage is mainly located in the esophageal mucosa and have different degrees. Special attention should be paid on such patients.

[Value of neutrophil-to-lymphocyte ratio in the classification diagnosis of coronavirus disease 2019].

OBJECTIVE: To investigate the clinical significance of neutrophil-to-lymphocyte ratio (NLR) in classification of patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective analysis was performed on 72 patients with COVID-19 admitted to the critical ward of Cancer Center of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan from February to March in 2020. The patients were divided into two groups: moderate type (non-severe group) and severe/critical type (severe group). The results of white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), interleukin-6 (IL-6) and D-dimer were collected at the 2nd day after admission from the two groups, and the NLR was calculated. The diagnostic value of WBC, NEU, LYM, IL-6, D-dimer and NLR on COVID-19 classification was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: A total of 72 COVID-19 patients were enrolled, among whom 52 were moderate, 17 were severe, and 3 were critical. The most common clinical manifestations of patients were fever (70.8%), cough (36.1%), chest tightness and breathlessness (37.5%), diarrhea (15.3%), fatigue (15.3%), vomiting and nausea (11.1%), occasionally accompanied by acute dyspnea (2.8%), and only one patient had no clinical symptom (1.4%). The levels of WBC, NEU, IL-6, D-dimer and NLR in the severe group were significantly higher than those in the non-severe group [WBC (×109/L): 7.81±3.65 vs. 5.34±1.69, NEU (×109/L): 5.83±3.13 vs. 3.24±1.53, IL-6 (ng/L): 133.63 (71.09, 249.61) vs. 28.05 (6.41, 101.24), D-dimer (mg/L): 0.86 (0.31, 2.56) vs. 0.33 (0.20, 0.71), NLR: 6.14±4.75 vs. 2.66±1.93, all P < 0.05], and the level of LYM was significantly lower than that in the non-severe group (×109/L: 1.09±0.56 vs. 1.49±0.74, P < 0.05). The results of ROC curve analysis showed that the areas under ROC curve (AUC) of WBC, NEU, LYM, IL-6, D-dimer and NLR for COVID-19 classification were 0.790 [95% confidence interval (95%CI) was 0.684-0.897), 0.869 (95%CI was 0.789-0.949), 0.719 (95%CI was 0.592-0.847), 0.790 (95%CI was 0.682-0.898), 0.676 (95%CI was 0.526-0.827), and 0.888 (95%CI was 0.814-0.963) respectively. The AUC of NLR was the highest, which was of high diagnostic value; when the optimum cut-off value of NLR was 3.00, the sensitivity was 100%, and the specificity was 73.1%. CONCLUSIONS: NLR can be used as a biomarker to predict classification of COVID-19 patients independently, which can provide a theoretical basis for the classification management of COVID-19 patients.

Cardiac injuries in patients with coronavirus disease 2019: Not to be ignored.

OBJECTIVE: To describe the clinical features of coronavirus disease 2019 (COVID-19). METHODS: We recruited 73 patients with COVID-19 [49 men and 24 women; average age: 58.36 years (SD: 14.31)] admitted to the intensive care unit of Wuhan Jinyintan Hospital from December 30, 2019 to February 16, 2020. Demographics, underlying diseases, and laboratory test results on admission were collected and analyzed. Data were compared between survivors and non-survivors. RESULTS: The non-survivors were older (65.46 [SD 9.74]vs 46.23 [12.01]) and were more likely to have chronic medical illnesses. Non-survivors tend to develop more severe lymphopenia, with higher C-reactive protein, interleukin-6, D-dimer, and hs-Troponin I(hs-TnI) levels. Patients with elevated hs-TnI levels on admission had shorter duration from symptom onset to death. Increased hs-TnI level was related to dismal prognosis. Death risk increased by 20.8% when the hs-TnI level increased by one unit. After adjusting for inflammatory or coagulation index, the independent predictive relationship between hs-TnI and death disappeared. CONCLUSIONS: Cardiac injury may occur at the early stage of COVID-19, which is associated with high mortality. Inflammatory factor cascade and coagulation abnormality may be the potential mechanisms of COVID-19 combined with cardiac injury.

[Influence of hypocalcemia on the prognosis of septic patients].

OBJECTIVE: To investigate the effect of serum calcium level on the prognosis of patients with sepsis. METHODS: Clinical data of 119 patients with sepsis admitted to intensive care medicine (ICU) of the First Affiliated Hospital of the University of Science and Technology of China from January 2017 to October 2018 were retrospectively analyzed. Gender, age, and C-reactive protein (CRP), procalcitonin (PCT), serum calcium levels, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure score (SOFA) within 24 hours of diagnosis, and 28-day mortality were collected. The patients were divided into the normal serum calcium group (serum calcium 2.00-2.67 mmol/L) and the hypocalcemia group (serum calcium < 2.00 mmol/L) according to their serum calcium level. The patients were divided into survival group and death group according to 28-day prognosis. Pearson correlation test was used to analyze the correlation between serum calcium level and clinical indicators. Receiver operator characteristic (ROC) curve was used to analyze the predictive value of serum calcium level on prognosis. RESULTS: A total of 119 patients with sepsis were included, including 50 patients with normal serum calcium, with serum calcium level of (2.14±0.10) mmol/L; and 69 patients of hypocalcemia, and the incidence of hypocalcemia was 57.98%, with serum calcium level of (1.81±0.14) mmol/L. In the hypocalcemia group, except that the APACHE II score was significantly higher than that of the normal serum calcium group (25.59±5.52 vs. 22.28±4.89, P < 0.01), there was no significant difference in gender, age, CRP, PCT and SOFA score between the two groups. The 28-day mortality rate of the hypocalcemia group was significantly higher than that of the normal serum calcium group [78.26% (54/69) vs. 48.00% (24/50), χ2 = 10.45, P < 0.01]. The level of serum calcium in the death group was significantly lower than that in the survival group (mmol/L: 1.90±0.20 vs. 2.04±0.19), while the APACHE II score was significantly higher than the survival group (25.78±5.25 vs. 21.20±4.68), with statistically significant differences (both P < 0.01). There was a negative correlation between serum calcium level and PCT, APACHE II scores in patients with sepsis (r1 = -2.10, P1 = 0.04; r2 = -3.91, P2 < 0.01), but no correlation with CRP and SOFA score (r1 = 0.75, P1 = 0.46; r2 = -1.21, P2 = 0.23). The ROC curve analysis showed that the area under the ROC curve (AUC) for predicting the prognosis of sepsis patients with serum calcium level was 0.70 [95% confidence interval (95%CI) = 0.602-0.798], and the best cut-off value was 1.92 mmol/L, with the sensitivity was 52.56%, and the specificity was 82.93%. CONCLUSIONS: The prognosis of sepsis patients with hypocalcemia is poor. Serum calcium level can be used as a predictor of prognosis in patients with sepsis.

[Clinical investigation on the risk factors for prognosis in patients with septic shock].

OBJECTIVE: To study the risk factors of prognosis in patients with septic shock, and to provide a reliable evidence to evaluate severity. METHODS: A retrospective analysis was conducted. The data of 185 patients with septic shock admitted to the intensive care unit (ICU) of Anhui Provincial Hospital Affiliated to Anhui Medical University from March 2016 to December 2018 were enrolled. Routine blood test, blood biochemistry, blood gas analysis, myoglobin (Myo), cardiac troponin I (cTnI), blood lactic acid (Lac), procalcitonin (PCT) and ratio of C-reactive protein and albumin (CRP/ALB) of patients on the day of septic shock diagnosis were collected. Glasgow coma scale (GCS), quick sequential organ failure assessment (qSOFA), acute physiology and chronic health evaluation II (APACHE II) and multiple organ dysfunction score (MODS) as well as the time from hospitalization to septic shock and duration of mechanical ventilation were recorded. The patients were divided into death group and survival group according to whether they survived or not on 28 days. According to Myo level, the patients were divided into two groups: Myo elevation group (Myo > 98 µg/L) and Myo normal group (Myo ≤ 98 µg/L). Patients with Myo elevation were divided into survival subgroup and death subgroup according to the prognosis of 28 days. The clinical data were compared among the groups, and the influencing factors of prognosis in septic shock patients were screened by multivariate Logistic regression analysis. RESULTS: 185 patients were all enrolled in the final analysis, there were 106 deaths and 79 survivors on 28 days, 154 patients with elevated Myo and 31 patients with normal Myo. (1) Compared with the patients with septic shock in the survival group, the death group had older patients, increased qSOFA, APACHE II, MODS scores and blood Myo, Lac, PCT levels, faster heart rate, decreased GCS score, and shorter time from hospitalization to septic shock and duration of mechanical ventilation. However, there was no significant difference in cTnI or CRP/Alb between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.037, 95% confidence interval (95%CI) was 1.010-1.065, P = 0.007], heart rate (OR = 1.020, 95%CI was 1.003-1.037, P = 0.023), qSOFA score (OR = 2.839, 95%CI was 1.321-6.102, P = 0.008), Myo (OR = 1.492, 95%CI was 1.088-2.045, P = 0.013), time from hospitalization to septic shock (OR = 0.938, 95%CI was 0.898-0.980, P = 0.004) and duration of mechanical ventilation (OR = 0.936, 95%CI was 0.899-0.975, P = 0.001) were independent risk factors for prognosis in patients with septic shock. (2) Compared with Myo normal group, the Myo elevation group had higher 28-day mortality [61.0% (94/154) vs. 38.7% (12/31), χ2 = 5.259, P = 0.022]. Compared with the survival patients with elevated Myo, the death patients were older, and had higher PCT and qSOFA score, faster heart rate, lower GCS score, and shorter time from hospitalization to septic shock and duration of mechanical ventilation. But there was no significant difference in CRP/Alb between the two groups. Multivariate Logistic regression analysis showed that qSOFA score (OR = 2.796, 95%CI was 1.270-6.153, P = 0.011), time from hospitalization to septic shock (OR = 0.925, 95%CI was 0.884-0.967, P = 0.001) and duration of mechanical ventilation (OR = 0.931, 95%CI was 0.884-0.980, P = 0.006) were independent risk factors for the prognosis in the septic shock patients with elevated blood Myo. CONCLUSIONS: Age, heart rate, qSOFA score, Myo, time from hospitalization to septic shock, duration of mechanical ventilation were independent risk factors for the prognosis of patients with septic shock. The 28-day mortality in patients with elevated blood Myo was significantly higher than that in those with normal blood Myo. The qSOFA score, time from hospitalization to septic shock and duration of mechanical ventilation were independent risk factors for the prognosis of septic shock patients with elevated blood Myo.

Protective effects of melatonin on sepsis-induced liver injury and dysregulation of gluconeogenesis in rats through activating SIRT1/STAT3 pathway.

Sepsis, a life-threatening disease with high morbidity and mortality in critically ill patients, usually leads to serious complications including liver damage and dysregulated metabolic homoeostasis. The aim of this study was to evaluate the therapeutic potential of melatonin in rats with caecal ligation and puncture (CLP)-induced sepsis, which mimics critical infections in humans and explore the underlying molecular mechanisms. Male Sprague-Dawley rats received CLP surgery under anaesthesia to induce polymicrobial sepsis. Melatonin (20 mg/kg) was intraperitoneally (i.p.) injected every 12 h for 7 days after CLP, with or without intraperitoneal injection of the SIRT1 inhibitor EX527 (5 mg/kg). Markers of glucose metabolism, inflammation, liver function and associated signaling pathway were measured. Septic rats exhibited marked inhibition of the hepatic SIRT1/STAT3 pathway, along with increased blood glucose levels and hepatic gluconeogenesis. Melatonin administration efficiently attenuated liver dysfunction and glucose metabolism disorders by promoting hepatic SIRT1 expression and STAT3 phosphorylation. Furthermore, inhibition of SIRT1 by EX527 significantly diminished the protective effects of melatonin on sepsis induced liver injury, hyperglycaemia and STAT3 inactivation. These results emphasize that melatonin is a potential therapeutic agent for sepsis-associated liver injury and glucose metabolism disorders, possibly acting by targeting SIRT1-mediated STAT3 activation in the liver.

[Study on the protective effect of ligustrazine on the transporting function of hepatocellular mitochondria membrane in the septic rats].

OBJECTIVE: To investigate the protective effect of ligustrazine on the transporting function of hepatocellular mitochondria membrane in the rats with sepsis-induced acute liver injury (SALI). METHODS: The Sprague-Dawley (SD) rats were randomly divided into sham operation group, SALI group [established by cecal ligation and puncture (CLP)], ligustrazine treatment group (injection of ligustrazine 60 mg/kg through tail vein after CLP) and ligustrazine preventive group (7 days before CLP, ligustrazine was injected daily through tail vein for 60 mg/kg), and there were 12 rats in each group. Abdominal aorta blood and liver were harvested at 10 hours after operation. The content of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and mitochondrial aspartate aminotransferase (m-AST) were determined by enzyme coupling rate method. The content of ATP was detected by colorimetric and chemical fluorescein method. The activity of mitochondrial ATPase was detected by phosphorus quantification. The expressions of mitochondrial membrane aquaporin 8 (AQP8) and carnitine palmitoyl transferase (CPT) were detected by Western Blot. RESULTS: Compared with sham operation group, the levels of serum ALT, AST and m-AST were significantly increased in SALI group, ligustrazine treatment group and ligustrazine preventive group, and the content of ATP was reduced, the activity of mitochondrial membrane ATPase, the expressions of AQP8 and CPT-1A were significantly decreased. Compared with SALI group, the levels of serum ALT, AST and m-AST were significantly decreased in ligustrazine treatment and ligustrazine preventive groups [ALT (U/L): 123.8±32.8, 105.0±44.5 vs. 233.0±110.1; AST (U/L): 427.0±117.9, 303.9±110.3 vs. 742.6±441.4; m-AST (U/L): 239.6±64.9, 168.2±60.0 vs. 412.8±252.6; all P < 0.01], the content of ATP were significantly increased (nmol/mg: 29.5±10.3, 34.6±11.2 vs. 19.3±8.8, both P < 0.01), the activity of ATPase in hepatocellular mitochondrial membrane were significantly increased [Na+-K+-ATPase (U/mg): 3.91±0.30, 3.97±0.35 vs. 2.87±0.82; Mg2+-ATPase (U/mg): 3.75±0.38, 3.88±0.35 vs. 2.64±1.06; Ca2+-ATPase (U/mg): 3.15±0.58, 2.98±0.31 vs. 1.75±1.25; Ca2+-Mg2+-ATPase (U/mg): 3.82±0.31, 3.91±0.42 vs. 2.57±1.01, all P < 0.01], the expressions of AQP8 and CPT-1A were significantly increased [percentage increase from sham operation group (100%), AQP8/COX-IV: (79.12±7.79)%, (88.40±9.22)% vs. (62.08±11.91)%; CPT-1A/COX-IV: (87.92±10.06)%, (84.91±17.48)% vs. (72.11±7.82)%, all P < 0.01]. The levels of serum AST and m-AST in ligustrazine preventive group were significant lower than those in ligustrazine treatment group [AST (U/L): 303.9±110.3 vs. 427.0±117.9; m-AST (U/L): 168.2±60.0 vs. 239.6±64.9, both P < 0.05]. There was no significant difference in the expression of CPT-2 in mitochondrial membrane between the four groups. CONCLUSIONS: Ligustrazine could play a protective role on the mitochondrial membrane function of transporting water, ion and fat in the rats with SALI. The preventive function of ligustrazine is better than the treatment effect of the rats with sepsis.