Serum lactate monitoring may help to predict neurological function impairment caused by acute metabolism crisis.

To investigate the predictive value of serum lactate on neurological function impairment and the possible etiology. In this retrospective study, all the adult patients admitted to ICU more than 24 h after general anesthesia elective neurosurgery from January 2018 to January 2019 were recruited. The data of the serum lactate every 8 h during the 24 h of ICU admission were acquired and analyzed. 169 patients were included in the outcomes analysis. The average serum lactate after ICU admission was 3.7(3.4-4.1) mmol/L, higher than normal, and serum lactate elevated commonly after neurosurgery. The serum lactate at ICU admission (lactateserum0h) was not correlated with the outcomes, whereas the predictive value increased as the monitoring time was extended. The result indicated that lactateserum8h, the lactateserum16h, and the lactateserum24h were correlated with the primary outcome (difference of GCS scores before the surgery and after 24 h of ICU admission (ΔGCS24h) (p < 0.05). The lactateserum16h and the lactateserum 24 h were correlated with all the outcomes except for the hospital LOS. The ROC curve suggested that the lactateserum24h achieved the best predictive value. Patients with serum lactate non-recovered trend after 24 h of ICU stay had decreased GCS scores and vice versa, as indicated by the graph of the dynamic changes in the serum lactate. The predictive value of the serum glucose/serum lactate ratio at ICU admission (G/Lserum) was analyzed, and the result indicated that it was correlated with the ΔGCS24h (p < 0.05), the G/Lserum can predict neurological impairment earlier. Dynamic serum lactate monitoring and the G/Lserum at ICU admission have predict value on neurological function impairment after neurosurgery which might be attributed to ACMC.

The role of BKCa in endometrial cancer HEC-1-B cell proliferation and migration.

BKCa is a large conductance calcium activated potassium channel ubiquitously expressed in various cell types. Accumulating evidence demonstrates that BKCa is aberrantly expressed in many malignancies, involving in cancerous behaviors such as cell proliferation and migration. In this study, we investigated the functional role of BKCa in endometrial cancer HEC-1-B cells. Overexpression of BKCa by plasmid transfection enhanced endometrial cancer cell proliferation and migration. Conversely, silence of BKCa by lentivirus mediated RNAi system not only inhibited proliferation and migration but also impaired tumor growth in vivo. Patch clamp assay identified the BKCa currents in HEC-1-B cells, which was supported by the observation of channel activation or inhibition in response to the specific opener (NS1619) or blocker (IBTX) of BKCa. Moreover, NS1619 significantly increased cell proliferation and migration while IBTX exhibited the opposite effects. In summary, these data suggested an important role of BKCa in proliferation and migration of endometrial cancer HEC-1-B cells. Thus, BKCa may be established as a potential therapeutic target in endometrial cancer.

Cytotoxic CD4+ T cells are correlated with better prognosis in Han Chinese grade II and grade III glioma subjects and are suppressed by PD-1 signaling.

PURPOSE: Malignant gliomas are the most common tumors in the central nervous system with a poor prognosis. Recently, CD4+ cytotoxic T cells (CTLs) are being increasingly recognized as possessing antitumor capacity. However, their presence, activity and regulation in glioma have not been investigated in detail. METHODS: To examine this, 72 grade II and grade III Han Chinese glioma patients and 30 Han Chinese healthy controls were investigated. RESULTS: We found that compared to healthy controls, glioma patients had significantly upregulated frequencies of circulating CD4+ CTLs, identified by the expression of granzyme A (GzmA), granzyme B (GzmB) and/or perforin. The stimulated CD4+ CTLs in grade II and grade III glioma patients also had less proliferative ability than those in healthy controls, a feature of suppression that progressed with tumor grade. The frequencies of GzmB-expressing circulating CD4+ CTLs were directly associated with prognosis. We hypothesized that the programed death 1 (PD-1)/PD-ligand 1 (L1) interaction possibly contributed to the suppression of CD4+ CTLs in grade II and grade III glioma, since an upregulation of PD-1 was observed on CD4+ CTLs in glioma compared to those in the healthy individuals. Blockade of the PD-1/PD-L1 interaction with neutralizing antibodies significantly increased the proliferation and granzyme or perforin production by CD4+ CTLs in grade II and grade III glioma patients. CONCLUSIONS: These data suggest that the CD4+ CTLs in grade II and grade III glioma patients contribute to antitumor immunity and could be suppressed by PD-1 signal transduction.

Ultrafine particles in the airway aggravated experimental lung injury through impairment in Treg function.

Acute lung injury (ALI) is a life-threatening condition characterized by rapid-onset alveolar-capillary damage mediated by pathogenic proinflammatory immune responses. Since exposure to airway particulate matter (PM) could significantly change the inflammatory status of the individual, we investigated whether PM instillation in the airway could alter the course of ALI, using a murine model with experimental lung injury induced by intratracheal LPS challenge. We found that PM-treated mice presented significantly aggravated lung injury, which was characterized by further reductions in body weight, increased protein concentration in the bronchoalveolar lavage (BAL), and higher mortality rate, compared to control saline-treated mice. The PM-treated mice also presented elevated lung and systemic type 1 T helper cell (Th1) frequency as well as reduced lung regulatory T cell (Treg) frequency, which was associated with severity of lung injury. Further examinations revealed that the Treg function was impaired in PM-treated mice, characterized by significantly repressed transforming growth factor beta production. Adoptive transfer of functional Tregs from control mice to PM-treated mice significantly improved their prognosis after intratracheal LPS challenge. Together, these results demonstrated that first, PM in the airway aggravated lung injury; second, severity of lung injury was associated with T cell subset imbalance in PM-treated mice; and third, PM treatment induced quantitative as well as qualitative changes in the Tregs.

Upregulation of CD19⁺CD24(hi)CD38(hi) regulatory B cells is associated with a reduced risk of acute lung injury in elderly pneumonia patients.

Acute lung injury (ALI) is a common complication in elderly pneumonia patients who have a rapid progression, and is accompanied by a high mortality rate. Because the treatment options of ALI are limited to supportive care, identifying pneumonia patients who are at higher risk of ALI development is the emphasis of many studies. Here, we approach this problem from an immunological perspective by examining CD19(+)CD24(hi)CD38(hi) B cells, an important participant in acute and chronic inflammation. We find that elderly pneumonia patients have elevated CD19(+)CD24(hi)CD38(hi) B cell frequency compared to healthy individuals. This B cell population may express a higher level of IL-10, which has been was shown to suppress CD4(+) T cell-mediated proinflammatory cytokine interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa) production, through an IL-10-dependent mechanism. We also observe that the frequency of CD19(+)CD24(hi)CD38(hi) B cell is positively correlated with the frequency of CD4(+)CD25(+)Foxp3(+)Tregs in peripheral blood. Moreover, consistent with CD19(+)CD24(hi)CD38(hi) B cell's anti-inflammatory role, we find that pneumonia patients who later developed ALI have reduced level of CD19(+)CD24(hi)CD38(hi) B cells. Together, our results demonstrated that CD19(+)CD24(hi)CD38(hi) B cells in pneumonia patients possess regulatory function in vivo, and are associated with a reduced ALI risk.

Regulatory B Cell Function Is Suppressed by Smoking and Obesity in H. pylori-Infected Subjects and Is Correlated with Elevated Risk of Gastric Cancer.

Helicobacter pylori infection occurs in more than half of the world's population and is the main cause for gastric cancer. A series of lifestyle and nutritional factors, such as tobacco smoking and obesity, have been found to elevate the risk for cancer development. In this study, we sought to determine the immunological aspects during H. pylori infection and gastric cancer development. We found that B cells from H. pylori-infected patients presented altered composition and function compared to uninfected patients. IL-10-expressing CD24+CD38+ B cells were upregulated in H. pylori-infected patients, contained potent regulatory activity in inhibiting T cell pro-inflammatory cytokine secretion, and responded directly to H. pylori antigen stimulation. Interestingly, in H. pylori-infected smoking subjects and obese subjects, the number of IL-10+ B cells and CD24+CD38+ B cells were reduced compared to H. pylori-infected asymptomatic subjects. Regulatory functions mediated by CD24+CD38+ B cells were also impaired. In addition, gastric cancer positive patients had reduced IL-10-producing B cell frequencies after H. pylori-stimulation. Altogether, these data suggest that in H. pylori-infection, CD24+CD38+ B cell is upregulated and plays a role in suppressing pro-inflammatory responses, possibly through IL-10 production, a feature that was not observed in smoking and obese patients.

Toll-like receptor 3 genetic variants and susceptibility to hepatocellular carcinoma and HBV-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with few treatment options. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and may affect the development of cancers. This study aimed to investigate whether TLR3 polymorphisms were associated with susceptibility to HCC. Two polymorphisms in the TLR3 gene, -976T/A and +1234C/T, were tested by polymerase chain reaction-restriction fragment length polymorphism in 466 HCC patients and 482 healthy controls. Results showed that the prevalence of +1234CT genotype and +1234TT genotype were significantly increased in the HCC cases than in controls (odds ratio [OR] =1.51; 95 % confidence interval [CI]; 1.22-1.93; p=0.004 and OR=3.19; 95 % CI, 1.82-5.39; p=1.99 × 10(-5), respectively). The -976T/A polymorphism did not reveal any differences between cases and controls. When analyzing the TLR3 +1234C/T polymorphism with different clinical parameters in HCC patients, the cases who were hepatitis B virus (HBV) carriers had higher number of +1234CT genotype and +1234T allele than those without HBV infection (p=0.032 and p=0.043). These data indicate that TLR3 +1234C/T polymorphism could be a novel risk factor for HCC, especially the HBV-related HCC.

A prospective randomized controlled trial to compare Pringle maneuver, hemihepatic vascular inflow occlusion, and main portal vein inflow occlusion in partial hepatectomy.

BACKGROUND: blood loss during liver resection and the need for perioperative blood transfusions have negative impact on perioperative morbidity, mortality, and long-term outcomes. METHODS: a randomized controlled trial was performed on patients undergoing liver resection comparing hemihepatic vascular inflow occlusion, main portal vein inflow occlusion, and Pringle maneuver. The primary endpoints were intraoperative blood loss and postoperative liver injury. The secondary outcomes were operating time, morbidity, and mortality. RESULTS: a total of 180 patients were randomized into 3 groups according to the technique used for inflow occlusion during hepatectomy: the hemihepatic vascular inflow occlusion group (n = 60), the main portal vein inflow occlusion group (n = 60), and the Pringle maneuver group (n = 60). Only 1 patient in the hemihepatic vascular occlusion group required conversion to the Pringle maneuver because of technical difficulty. The Pringle maneuver group showed a significantly shorter operating time. There were no significant differences between the 3 groups in intraoperative blood loss and perioperative mortality. The degree of postoperative liver injury and complication rates were significantly higher in the Pringle maneuver group, resulting in a significantly longer hospital stay. CONCLUSIONS: all 3 vascular inflow occlusion techniques were safe and efficacious in reducing blood loss. Patients subjected to hemihepatic vascular inflow occlusion, or main portal vein inflow occlusion responded better than those with Pringle maneuver in terms of earlier recovery of postoperative liver function. As hemihepatic vascular inflow occlusion was technically easier than main portal vein inflow occlusion, it is recommended.