Case Report: Langerhans Cell Sarcoma With Intracranial and Extracranial Communication on the Left Frontal Bone.

Background: Langerhans cell sarcoma (LCS) is an extremely rare type of malignant tumor that originates from Langerhans cells (LC). It is characterized by the malignant proliferation and dissemination of LC and is extremely invasive, with rapid progression and a poor prognosis. Treatment includes resection of lesions, radiotherapy, chemotherapy, immunotherapy, and transplantation of hematopoietic stem cells. However, a unified and optimized treatment plan is lacking, and individualized treatment is accepted. Case presentation: We report an 18-year-old man with intracranial and extracranial communicative LCS that occurred in only the left forehead without metastasis to other regions. Clinical and hematological data were normal. We undertook complete resection of diseased tissue, which was pathologically examined. Staining (hematoxylin and eosin) showed positivity for cluster of differentiation (CD)1a (++), S-100 protein (++), P53 (++), CD68 (+), cyclin D1 (+), cyclin A (+), cyclin B1 (+), IGF2BP3 (+), and Ki-67 (45%-50%). Recurrence or metastasis were not observed after long-term follow-up. Conclusion: LCS is a rare malignant tumor, and one that occurs with intracranial and extracranial communication is even rarer. Active adoption of an individualized treatment plan is crucial.

[Effects of different target blood pressure resuscitation on peripheral blood inflammatory factors and hemodynamics in patients with traumatic hemorrhagic shock].

OBJECTIVE: To investigate the target blood pressure level of restrictive fluid resuscitation in patients with traumatic hemorrhagic shock. METHODS: Sixty patients with traumatic hemorrhagic shock admitted to the First Affiliated Hospital of Bengbu Medical College from January 2016 to December 2018 were enrolled. All patients were resuscitated with sodium acetate ringer solution after admission. According to the difference of mean arterial pressure (MAP) target, the patients were divided into low MAP (60 mmHg ≤ MAP < 65 mmHg, 1 mmHg = 0.133 kPa), middle MAP (65 mmHg ≤ MAP < 70 mmHg) and high MAP (70 mmHg ≤ MAP < 75 mmHg) groups by random number table using the admission order with 20 patients in each group. Those who failed to reach the target MAP after 30-minute resuscitation were excluded and supplementary cases were deferred. The restrictive fluid resuscitation phase was divided into three phases: before fluid resuscitation, liquid resuscitation for 30 minutes and 60 minutes. The most suitable resuscitation blood pressure level was further speculated by monitoring the inflammatory markers and hemodynamics in different periods in each group of patients. Pearson correlation analysis was used to detect the correlation of variables. RESULTS: Before fluid resuscitation, there was no significant difference in hemodynamics or expressions of serum cytokines among the three groups. Three groups of patients were resuscitated for 30 minutes to achieve the target blood pressure level and maintain 30 minutes. With the prolongation of fluid resuscitation time, the central venous pressure (CVP), cardiac output (CO) and cardiac index (CI) were increased slowly in the three groups, and reached a steady state at about 30 minutes after resuscitation, especially in the high MAP group and the middle MAP group. The expressions of serum inflammatory factors in the three groups were gradually increased with the prolongation of fluid resuscitation time. Compared with the low MAP group and the high MAP group, after 30 minutes of resuscitation the middle MAP group was superior to the other two groups in inhibiting the expressions of pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and promoting anti-inflammatory factors IL-10 [TNF-α mRNA (2-ΔΔCt): 0.21±0.13 vs. 0.69±0.34, 0.57±0.35; IL-6 mRNA (2-ΔΔCt): 0.35±0.31 vs. 0.72±0.39, 0.59±0.42; IL-10 mRNA (2-ΔΔCt): 1.25±0.81 vs. 0.61±0.46, 0.82±0.53; all P < 0.05], but there was no significant difference in promoting the expression of IL-4 mRNA among three groups. At 60 minutes of resuscitation, compared with the low MAP group and the high MAP group, the middle MAP group could significantly inhibit the expressions of TNF-α, IL-6 and promote IL-10 [TNF-α mRNA (2-ΔΔCt): 0.72±0.35 vs. 1.05±0.54, 1.03±0.49; IL-6 mRNA (2-ΔΔCt): 0.57±0.50 vs. 1.27±0.72, 1.01±0.64; IL-10 mRNA (2-ΔΔCt): 1.41±0.90 vs. 0.81±0.48, 0.94±0.61; all P < 0.05]. Compared with the high MAP group, the middle MAP group had significant differences in promoting the expression of IL-4 mRNA (2-ΔΔCt: 1.32±0.62 vs. 0.91±0.60, P < 0.05). There was no significant difference in serum cytokine expressions at different time points of resuscitation between the low MAP group and the high MAP group (all P > 0.05). Correlation analysis showed that there was a strong linear correlation between MAP and mRNA expressions of TNF-α, IL-6, IL-10 in the middle MAP group (r value was 0.766, 0.719, 0.692, respectively, all P < 0.01), but had no correlation with IL-4 (r = 0.361, P = 0.059). Fitting linear regression analysis showed an increase in 1 mmHg per MAP, the expression of TNF-α mRNA increased by 0.027 [95% confidence interval (95%CI) = 0.023-0.031, P < 0.001], IL-6 mRNA increased by 0.021 (95%CI = 0.017-0.024, P < 0.001), and IL-10 mRNA increased by 0.049 (95%CI = 0.041-0.058, P < 0.001). CONCLUSIONS: When patients with traumatic hemorrhagic shock received restrict fluid resuscitation at MAP of 65-70 mmHg, the effect of reducing systemic inflammatory response and improving hemodynamics is better than the target MAP at 60-65 mmHg or 70-75 mmHg. It is suggested that 65-70 mmHg may be an ideal target MAP level for restrictive fluid resuscitation.

[IL-12 monoclonal antibody alleviates intestinal inflammation in IL-10-/- mice by regulating intestinal mucosal immunity].

Objective To evaluate the therapeutic effect and possible mechanism of IL-12 monoclonal antibody (IL-12 mAb) on IL-10 knockout(IL-10-/-) mice and its possible mechanism. Methods Sixteen male IL-10-/- mice of 15 weeks old were randomly divided into control group and IL-12 mAb treatment group. The IL-12 mAb treatment group were given intraperitoneal injection of IL-12 mAb (25 mg/kg, once per week), and the control group was given intraperitoneal injection of 0.2 mL of normal saline. After 4 weeks of intervention, the inflammatory bowel disease activity index (DAI) and HE staining were used to evaluate the intestinal inflammation symptoms and histological changes. The intestinal mucosal permeability test was used to evaluate the intestinal mucosal barrier function of the two groups. The expression of claudin-1 in intestinal mucosa was detected by Western blot analysis. The Th1/Th2 cell balance of intestinal mucosa was evaluated by flow cytometry. The ELISA was used to evaluate IL-13 and tumor necrosis factor alpha(TNF-α) of intestinal mucosal of the two groups. The expression of phosphorylated signal transducer and activator of transcription (p-STAT6) in intestinal mucosa was detected by Western blot nanlysis. Results Three and 4 weeks after IL-12 mAb treatment, the DAI and intestinal inflammation scores of IL-12 mAb treatment group were significantly lower than the control group. At the same time, the intestinal mucosal permeability of IL-12 mAb treatment group was significantly lower than that of the control group, and the expression of claudin-1 in intestinal mucosa was significantly higher than that of the control group. At the same time, IL-12 mAb treatment inhibited the proportion of Th1 cells in the intestinal mucosa and up-regulated the proportion of Th2 cells. In the signal pathway analysis, IL-12 mAb treatment increased the levels of p-STAT6 and IL-13 in the intestinal mucosa and inhibited the level of TNF-α. Conclusion IL-12 mAb effectively alleviates intestinal inflammation in the Crohn's disease animal model and protect the intestinal mucosal barrier, which may be through inhibition of Th1 cell immune response in the intestinal mucosa and up-regulation of STAT6 signaling.

[Rosiglitazone ameliorates TNBS-induced colitis in mice by inhibiting inflammation of the mesenteric adipose tissues].

Objective To evaluate the therapeutic effect and possible mechanism of PPARγ agonist rosiglitazone on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice. Methods Twenty male BALB/c mice were selected to establish TNBS-induced colitis model and were randomly divided into rosiglitazone treated group and model group with 10 rats in each group. Rosiglitazone group was treated with rosiglitazone(0.2 mL, [20 mg/(kg.d)])and model group with normal saline(0.2 mL/d). After 6 weeks of administration, the mice were sacrificed. Inflammatory bowel disease disease activity index (DAI) and HE staining combined with Spencer colitis histological score were used to evaluate the degree of intestinal inflammation and histological changes in the two groups. ELISA was used to detect the levels of interleukin-1ß (IL-1ß), tumor necrosis factor alpha(TNF-α) and IL-10 in the intestinal mucosa, the levels of IL-6 and monocyte chemoattractant protein 1 (MCP-1) in the mesenteric adipose tissues. The mean diameter of adipocytes in the mesenteric adipose tissues was calculated under light microscope after HE staining.The number of F4/80+ macrophages and the expressions of peripherin, adiponectin and leptin in mesenteric adipose tissues were detected by immunohistochemical staining. The phosphorylation of NF-κBp65, IKK, IκB proteins in the mesenteric adipose tissues was detected by Western blot analysis. Results The DAI score of rosiglitazone group was significantly lower than that of model group at 5 and 6 weeks after rosiglitazone treatment. At the same time, the levels of IL-1ß and TNF-α in the intestinal mucosa of the treated group were significantly lower than those in the model group, while the IL-10 levels were significantly higher in the treated group than in the model group. Compared with the model group, the mesenteric adipocyte diameter and the perilipin level of adipocyte maturation markers in rosiglitazone treated mice were significantly higher than those in model group. Meanwhile, the number of infiltration of macrophages in mesenteric adipose tissues of mice treated with rosiglitazone and the levels of inflammatory mediators IL-6 and MCP-1 were significantly lower than that of the model group. Rosiglitazone significantly promoted the expression of adiponectin and inhibited the expression of leptin in mesenteric adipocytes. The phosphorylation of NF-κBp65, IKK and IκB proteins in mesenteric adipose tissues of rosiglitazone treated mice was significantly lower than those of model group. Conclusion Rosiglitazone significantly inhibites intestinal inflammation in TNBS-induced colitis in mice, which may be related to the inhibition of NF-κBp65 pathway in mesenteric adipose tissues.