[Mechanism of n-butanol extract of Pulsatilla Decoction in treating ulcerative colitis by activating BMP signaling pathway].

The study aimed to investigate the therapeutic effects of the n-butanol extract of Pulsatilla Decoction(BEPD) on ulcerative colitis(UC) via the bone morphogenetic protein(BMP) signaling pathway. C57BL/6 mice were divided into six groups: control, model, mesalazine, and BEPD low-, medium-, and high-dose groups. Except for the control group, the rest groups were treated with 3% dextran sulfate sodium(DSS) freely for seven consecutive days to establish the UC mouse model, followed by treatment with different concentrations of BEPD and mesalazine by gavage. The murine body weight and disease activity index(DAI) were recorded. After the mice were sacrificed, their colon tissues were collected for histological analysis. Alcian blue/periodic acid-Schiff(AB/PAS) staining was used to detect the number and mucus secretion status of goblet cells; immunohistochemistry was performed to measure the expression of ki67, cleaved caspase-3, mucin 2(Muc2), and matrix metalloproteinase-9(MMP9) in colon tissues; and immunofluorescence was used to analyze the expression of tight junction proteins in colon tissues, and enzyme linked immunosorbent assay(ELISA) was employed to quantify the levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1ß, and IL-6. Western blot was conducted to evaluate the expression of BMP pathway-related proteins in mouse colon tissues. Quantitative real-time PCR(qRT-PCR) was performed to measure the expression of genes related to goblet cell differentiation in mouse colon tissues. In addition, this study also examined the protective effect and underlying mechanism of BEPD-containing serum on lipopolysaccharide(LPS)-induced barrier damages in LS174T goblet cells in vitro. The results showed that BEPD significantly alleviated UC symptoms in mice, restored goblet cell diffe-rentiation function, promoted Muc2 secretion and tight junction protein expression, and suppressed inflammatory factor secretion while activating the BMP signaling pathway. Therefore, BEPD may exert its therapeutic effects on UC by activating the BMP signaling pathway, providing a new strategy for drug intervention in UC.

[Mechanism of Shenling Baizhu Powder in alleviation of ulcerative colitis in mice based on high-throughput transcriptome sequencing].

High-throughput transcriptome sequencing was used to study the mechanism of Shenling Baizhu Powder(SLBZP) in the alleviation of the dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice. The mouse model of DDS-induced UC was treated with SLBZP by gavage. The changes in general state, disease activity index(DAI), and colon length were observed. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissues of mice. Enzyme-linked immunosorbent assay(ELISA) was used to determine the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1ß, IL-6, IL-4, and IL-10 in the serum and tissues of mice. The differentially expressed genes in the control group, the model group, and the SLBZP group were analyzed by high-throughput transcriptome sequencing, and the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were conducted on the differentially expressed genes. The results showed that after intragastric administration of SLBZP, the symptoms of diarrhea and bloody stool were improved, and the disease active index(DAI) score was reduced. SLBZP effectively reduced the inflammatory cell infiltration and goblet cell loss in the colonic mucosal tissue, reduced the levels of TNF-α, IL-1ß, IL-6 in the serum and colon tissue, and increased the levels of IL-4 and IL-10 in the serum and colon tissue. There were 25 differential genes in SLBZP vs the model group, which were significantly enriched in immune response, immune system process, immunoglobulin production, and other biological processes. KEGG pathway analysis showed that the differential genes were enriched in signaling pathways such as neomycin, kanamycin, and gentamicin biosynthesis, cytokine-cytokine receptor interaction, primary immunodeficiency, and IgA synthesis of the intestinal immune network. This study shows that SLBZP may alleviate UC through immune regulation.

TWIST1 transcriptionally regulates glycolytic genes to promote the Warburg metabolism in pancreatic cancer.

Reprogrammed glucose metabolism is essential for tumor initiation and development, especially for pancreatic ductal adenocarcinoma (PDAC). Most cancer cells rely on aerobic glycolysis, a phenomenon termed "the Warburg effect", to support uncontrolled proliferation and evade apoptosis. However, the direct regulators of the Warburg effect remain areas of active investigation. In this study, we found that the highly conserved transcription factor, TWIST1, is a crucial regulator of aerobic glycolysis in PDAC. Genetic silencing of TWIST1 significantly inhibited the glycolytic phenotypes of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate, which can be restored by re-expression of siRNA-resistant TWIST1. Moreover, tamoxifen-inducible expression of TWIST1 promoted the Warburg metabolism of PDAC cells. Mechanistically, by luciferase reporter assay and chromatin immunoprecipitation experiment, we showed that TWIST1 can directly increase the expression of several glycolytic genes, including SLC2A1, HK2, ENO1, and PKM2. Of note, the transcriptional regulation by TWIST1 was not dependent on HIF1α or c-Myc. In The Cancer Genome Atlas and Gene Expression Omnibus accession GSE15471, we confirmed that TWIST1 was closely associated with the glycolysis pathway. Collectively, our findings indicate that TWIST1 is likely to act as important regulator of the Warburg effect in PDAC.

Repeated postoperative adjuvant TACE after curative hepatectomy improves outcomes of patients with HCC.

BACKGROUND AND AIMS: To gain a clear picture of the influence of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on recurrence after curative resection for HCC. MATERIAL AND METHODS: According to the inclusion criteria and the exclusion criteria, the clinical data of 118 patients with HCC at Qilu Hospital, Shan Dong University between January 2011 and August 2013, who were treated by curative hepatectomy and postoperative TACE (two groups of patients received TACE once or twice, respectively) or by curative hepatectomy alone were retrospectively studied. RESULTS: The three-year survival (RFS) rate was 51.7% for the whole study population. The three-year relapse-free RFS rates were 73.0% and 55.0% for the patients who received two and one postoperative adjuvant TACE treatments, groups respectively, and 29.3% for the hepatectomy alone group. The three-year RFS of the patients who received postoperative adjuvant TACE once was significantly higher than that of the patients who received hepatectomy alone (p = .024). And the outcome of patients with two adjuvant TACE treatments was better than that of patients who received one treatment (p = .033). CONCLUSIONS: Repeated postoperative adjuvant TACE seems to be a promising treatment for HCC that might delay tumor recurrence and improve the RFS rates of patients after curative hepatectomy.

[Main components in butyl alcohol extract of Baitouweng Decoction inhibited neutrophil chemotaxis].

The present study aims to investigate the effects of the main components(aesculin, berberine hydrochloride, and anemoside B4) in the butyl alcohol extract of Baitouweng Decoction(BAEB) on the chemotaxis of neutrophils induced by dimethyl sulfoxide(DMSO). HL60 cells were cultivated in RPMI-1640 complete medium, and transferred into a 6-well plate(2 × 10~5 per mL) with 4 mL in each well, followed by incubation with DMSO at 1.3% for five days. The morphologic changes of cells were observed under an inverted microscope. The CD11 b expression after DMSO induction was analyzed by flow cytometry. The effects of aesculin, berberine hydrochloride, and anemoside B4 on the cell proliferation and migration were detected by CCK8 assay and Transwell assay, respectively. The effects of the main components on the production and polarization of F-actin protein were also examined by flow cytometry and laser confocal microscopy. PI3 K/Akt signaling pathway was checked by Western blot. As revealed by the results, neutrophil-like HL60 cells were observed after DMSO induction. The CD11 b expression in these cells increased significantly as indicated by the flow cytometry. Additionally, 100 µg·mL~(-1) aesculin, 8 µg·mL~(-1) berberine hydrochloride, and 80 µg·mL~(-1) anemoside B4 were potent in inhibiting the migration of neutrophils and reducing F-actin expression. Berberine hydrochloride was verified to be capable of diminishing phosphorylated PI3 K/Akt protein expression. The findings indicate that aesculin, anemoside B4, and especially berberine hydrochloride in the BAEB can inhibit the chemotaxis of neutrophils, which is possibly achieved by the inhibition of F-actin and PI3 K/Akt signaling pathway.

[Effect of berberine hydrochloride on cell wall integrity of Candida albicans hypha].

The aim of this paper was to investigate the effect of berberine hydrochloride on the cell wall integrity of Candida albicans hypha. The minimal inhibitory concentration(MIC) of berberine hydrochloride against clinical and standard C. albicans strains was detected by micro liquid-based dilution method; the effect of berberine hydrochloride on the colony formation of C. albicans SC5314 was investigated by spot assay; the effect of berberine hydrochloride on the metabolism of C. albicans SC5314 hypha was checked by XTT reduction assay, and the viability of C. albicans SC5314 hypha was tested by fluorescent staining assay. The effect of berberine hydrochloride on the morphology of C. albicans SC5314 hypha was examined by scanning electron microscope. The changes in the cell wall of C. albicans SC5314 hypha after berberine hydrochloride treatment were detected by transmission electron microscopy. The effect of berberine hydrochloride on ß-glucan from C. albicans SC5314 was detected by flow cytometry. The effect of berberine hydrochloride on hypha-specific gene ECE1 and ß-glucan synthase genes FKS1 and FKS2 in C. albicans was examined by qRT-PCR. The results showed that berberine hydrochloride showed a strong inhibitory effect on both clinical and standard strains of C. albicans, and the MIC was 64-128 µg·mL~(-1). Spot assay, XTT redunction assay and fluorescent staining assay showed that with the increase of berberine hydrochloride concentration, the viability of C. albicans SC5314 gradually decreased. The transmission electron microscopy scanning assay showed that this compound could cause cell wall damage of C. albicans. The flow cytometry analysis showed the exposure degree of C. albicans ß-glucan. The qRT-PCR further showed that berberine hydrochloride could significantly down-regulate hypha-specific gene ECE1 and ß-glucan synthase-related gene FKS1 and FKS2. In conclusion, this compound can down-regulate C. albicans and ß-glucan synthase-related gene expressions, so as to destroy the cell wall structure of C. albicans, expose ß-glucan and damage the integrity of the wall.

Metformin alleviates inflammatory response in non-alcoholic steatohepatitis by restraining signal transducer and activator of transcription 3-mediated autophagy inhibition in vitro and in vivo.

Autophagy is an intracellular recycling and degradation process for regulating cell survival and drug resistance. Non-alcoholic steatohepatitis (NASH) is becoming a widespread disease in developing countries. However, the role of autophagy in NASH has not yet been fully elucidated. The present study determined that signal transducer and activator of transcription 3 (STAT3), in the inflammation and autophagy regulation, was the key in the progression of NASH. In NASH mouse and cell models, STAT3 mRNA and protein expressions were significantly increased, while the induction of autophagy was radically decreased. Furthermore, the effects of metformin on STAT3 expression level and NASH inflammation were investigated. The current results showed that metformin activated autophagy and decreased the mRNA expressions of inflammatory cytokines, IL-1ß, IL-6, and TNF-α via inhibition of the STAT3 mRNA and protein expression. The siRNA targeting STAT3 activated autophagy and inhibited the NASH inflammatory response by reducing the mRNA expressions of the inflammatory cytokines in vivo and in vitro. The correlation between autophagy and inflammation was also explored. Autophagy induced by metformin attenuated the inflammatory response. This phenomenon of inflammation reduction was partially restored by treatment with the autophagy inhibitor 3-methylindole (3-MA). In conclusion, this study demonstrated that metformin alleviated the inflammatory response in the liver and the hepatocyte of the NASH model via STAT3-mediated autophagy induction. This mechanism provides a strategy for targeting the NASH inflammatory response.

Risk factors associated with the detection and missed diagnosis of colorectal flat adenoma: a Chinese multicenter observational study.

OBJECTIVES: Flat colorectal adenomas have a high risk of malignancy; however, their detection is often difficult due to their flat morphology. In this retrospective, large-scale study, we investigated the prevalence and characteristics of flat adenomas in a population in China. METHODS: We analyzed the data collected for 16951 consecutive patients who underwent colonoscopy at four participating hospitals between September 2013 and September 2015. All colonoscopies were performed without magnification. RESULTS: Among the 1,6951 patients, 2938 (17.3%) had adenoma and 796 (4.7%) had flat adenomas. The detection of flat adenoma showed a weak correlation with the detection of adenoma (r = 0.666). Multivariable logistic regression analysis revealed the following independent factors influencing the detection of flat adenomas: patient-related factors of age, presence of warning symptoms, history of adenomas and bowel preparation as well as endoscopist-related factors of endoscopist's level of proficiency, number of colonoscopy operators and withdrawal time. CONCLUSIONS: The prevalence of flat adenomas in our study on Chinese patients was consistent with that reported from other countries. Factors conducive to the detection of flat adenomas were patient age of > 60 years, warning symptoms, history of adenoma, good bowel preparation, experienced endoscopist, single-operator colonoscopy and colonoscopy withdrawal time of >6 min.

Degradable Chitosan-Collagen Composites Seeded with Cells as Tissue Engineered Heart Valves.

BACKGROUND: Degradable collagen-chitosan composite materials have been used to fabricate tissue engineered heart valves. The aims of this study were to demonstrate that the collagen-chitosan composite scaffolds are cytocompatible, and endothelial cells can be differentiated from bone marrow mesenchymal stem cells (BMSCs) when seeded onto the scaffolds. The adhesion and biological activities of the seeded cells were also investigated. METHODS: Collagen-chitosan composite material was used as the cell matrix, and smooth muscle cells, fibroblasts and BMSCs were used as seed cells. After four weeks of in vitro culture, the smooth muscle cells, fibroblasts, and BMSCs were sequentially seeded into the collagen-chitosan composite material. After four weeks in culture, the cellular density and activity were assessed on segments of the tissue engineered heart valve scaffolds to determine the cell viability and proliferation in the collagen-chitosan composite material. RESULTS: The tissue engineered heart valves stained positively for both smooth muscle actin and endothelial cell factor VIII, suggesting that the seeded cells were in fact smooth muscle cells, fibroblasts, and endothelial cells. The 6-ketone prostaglandin content, as measured by radioimmunoassay, of the collagen-chitosan cell culture fluid was higher than that of the serum-free medium (P <0.01). Light and electron microscopy showed that the seeded cells had shapes similar to the morphology of smooth muscle cells, fibroblasts, and endothelial cells. CONCLUSIONS: Endothelial cells can be differentiated from BMSCs when seeded onto the collagen-chitosan composite scaffolds. The seeded cells retained their biological activity after being cultured in vitro and seeded into the collagen-chitosan composite material.

lincRNA-p21 inhibits invasion and metastasis of hepatocellular carcinoma through Notch signaling-induced epithelial-mesenchymal transition.

AIM: Emerging evidence has showed that long non-coding RNA (lncRNA) play an important role in the occurrence and development of various cancers. In the present study, the expression level of lincRNA-p21 was investigated in hepatocellular carcinoma (HCC), and its role in invasion of HCC was also explored. METHODS: The lincRNA-p21 levels in human HCC tumor tissue and cell lines HepG2 and SMMC-7721 were determined by real-time polymerase chain reaction. Transfected HCC cells with pcDNA-lincRNA-p21 or si-lincRNA-p21 for overexpression or downregulation of lincRNA-p21, the Notch signaling and epithelial-mesenchymal transition (EMT)-related proteins and cell invasion were measured by western blot and Transwell assay, respectively. A tumor xenotransplant mouse model was also established to investigate the role of lincRNA-p21 in tumor metastasis in vivo. RESULTS: The lincRNA-p21 expression was downregulated in HCC tissue and cells. Overexpression of lincRNA-p21 inhibited Notch singling and EMT, while its downregulation led to the reverse result. The invasion of HCC cell was also inhibited by pcDNA-lincRNA-p21, and activation of Notch signaling reversed this effect. In vivo, overexpression of lincRNA-p21 decreased the tumor metastasis, as well. CONCLUSION: lincRNA-p21 was downregulated in HCC and lincRNA-p21 overexpression contributed to the inhibition of tumor invasion through mediating Notch signaling induced EMT.

The relationship between hepatic resistin overexpression and inflammation in patients with nonalcoholic steatohepatitis.

BACKGROUND: The relationship between resistin and non-alcoholic steatohepatitis (NASH) is not clear, some studies claimed that serum resistin levels were associated with neither the presence of NASH nor its severity, others declared that serum resistin was related with inflammation and fibrosis in NASH. Our animal study verified that the distribution of resistin in the liver is correlated with inflammation in NASH. However, there is no pertinent study in humans. METHODS: Thirty patients with NASH, 28 simple steatosis, and 43 controls were recruited. Blood was collected for resistin, liver chemistries, fasting insulin and some metabolic parameters. Liver histology was scored according to NAFLD activity scoring system. Hepatic resistin expression was examined by real-time polymerase chain reaction, immunohistochemistry. Resistin protein expression was confirmed by western blotting in 13 patients with concomitant NAFLD and gallstone. RESULTS: Serum resistin was significantly elevated in both NASH and simple steatotic subjects compared with controls (all P < 0.05). Hepatic resistin was significantly increased in NASH patients in both mRNA and protein levels than those in simple steatosis and control subjects (all P < 0.05). Both serum and hepatic resistin had a correlation with obesity, but not with insulin resistance. The distribution of resistin positive cells was predominantly in perisinusoidal cells (such as Kupffer cells and hepatic stellate cells) in human NASH. Multivariate analysis revealed that waist-hip ratio, higher serum triglyceride, and hyperresistinemia were independent factors related to higher grade of steatosis; whereas hepatic resistin and serum cytokeratin predict NASH and severity of liver fibrosis. CONCLUSIONS: Hepatic resistin overexpression in NASH patients is associated with the severity of liver inflammation and fibrosis. Liver-derived resistin may be involved in the pathogenesis of human NASH.

The complete mitochondrial genome of Anidiocerus bimaculatus Zhang, Li & Qi, 2008 (Hemiptera: Cicadellidae: Eurymelinae: Idiocerini).

In this study, the complete mitochondrial genome of Anidiocerus bimaculatus was sequenced and annotated for the first time, which belongs to the subfamily Eurymelinae. The mitogenome of A. bimaculatus was 15,267 bp in length and contained 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and one non-coding control region. In this mitogenome, all the PCGs are initially encoded by ATT, ATA, ATG, or TTG, and terminated by TAA, or single T. The overall base composition of A. bimaculatus is 43.6% adenines, 36.0% thymines, 9.1% guanines, and 11.3% cytosines. ML phylogenetic analyses confirmed that Idiocerini forms a monophyletic clade and the newly sequenced A. bimaculatus clustered within the Idiocerini clade based on 13 protein-coding genes and two rRNA genes.

Virological responses in chronic hepatitis C patients undergoing prolonged therapy with low-dose Peg-IFNα-2a.

BACKGROUND/AIMS: Standard dose therapy with pegylated interferon α-2a (Peg-IFNα-2a) and ribavirin is not suitable for all patients because of the side effects. This study aims to evaluate the virological responses of low-dose but long-course Peg-IFNα-2a therapy compared with standard therapy. METHODOLOGY: Ninety patients with chronic hepatitis C were divided into three groups according to their tolerance to Peg-IFNα-2a. The courses of treatment were 96 or 48 weeks respectively in patients with HCV genotypes 1b or 2a in the 67.5 µg and 90 µg groups, and were 48 or 24 weeks in the 180 µg groups. Serum HCV RNA was quantified to determine RVR, EVR, SVR and ETR. RESULTS: There were no statistical differences in HCV RNA load, HCV genotype at the baseline of the three groups (p>0.05). The rates of RVR, EVR, SVR and ETR (no significant differences in each group), were 63.04%, 82.61%, 71.74% and 85.87% in all 92 patients. Genotype 1b (95% CI=11.97-82.89; p=0.0075) and RVR (95% CI=0.12-0.53; p<0.001) were important predictors of SVR. CONCLUSIONS: Patients with low-dose but long-course Peg-IFNα-2a therapy had similar virological responses compared to those with standard therapy. HCV genotype and RVR were independent predictors of SVR.

Successful treatment of veno-arterial extracorporeal membrane oxygenation complicated with left ventricular thrombus by intravenous thrombolysis: A case report.

BACKGROUND: Left ventricular thrombus is a rare condition, for which appropriate treatments are not extensively studied. Although it can be treated by thrombectomy, such surgery can be difficult and risky, and not every patient can tolerate the surgery. CASE SUMMARY: We report a case of a middle-aged man receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for acute myocardial infarction who developed left ventricular thrombus despite systemic anticoagulation. After systemic thrombolysis with urokinase, the left ventricular thrombus disappeared, ECMO was successfully withdrawn 9 days later, and the patient recovered and was discharged from hospital. CONCLUSION: Systemic thrombolysis is a treatment option for left ventricular thrombus in addition to anticoagulation and thrombectomy.

Primary hepatic amyloidosis: a mini literature review and five cases report.

Primary hepatic amyloidosis (PHA) is characterized by abnormal deposition of monoclonal immunoglobulin light chains (AL) in the liver. This rare condition is frequently undiagnosed or misdiagnosed and can be associated with poor prognosis. At present, the precise pathogenesis is not fully understood. Despite that hepatomegaly and elevated alkaline phosphatase (ALP) are present in most patients with PHA, no specific clinical markers have been identified. Staining of hepatic tissues with Congo Red is often regarded as the "gold standard". Pharmacological therapy should aim to rapidly reduce the supply of misfolded amyloidogenic AL. High-dose intravenous melphalan (HDM) and autologous stem cell transplantation (ASCT) appear to be the most appropriate therapy but controversies still exist.

Improved efficacy by individualized combination therapy with Peg IFN-a 2a and ADV in HBeAg positive chronic hepatitis B patients.

BACKGROUND/AIMS: Monotherapy with pegylated interferon alpha (Peg-IFNa) or adefovir dipivoxil (ADV) to HBeAg-positive chronic hepatitis B (CHB) patients has limited effects. This study aims to evaluate therapeutic efficacy and safety of individualized combination therapy with Peg-IFNa and ADV. METHODOLOGY: HBeAg-positive CHB patients (n=160) were enrolled in this multi-center, prospective, randomized, 'real-life' cohort study, of which received Peg IFNa-2a monotherapy or combination therapy with ADV base on the baseline features and treatment response. RESULTS: At week 24, percentages of ALT normalization, HBV DNA undetectable were both higher in individualized treatment group (ITG, 57.50%, 43.75%) than that in standard treatment group (STG, 40.00%, 27.50%; p=0.027, 0.032). The superiority of HBeAg clearance and seroconversion rates in ITG maintained from treatment termination (63.75%, 56.25%) to 48 weeks follow-up (57.50%, 53.75%). At week 96 the combined response rates were 46.25% in ITG compared with 30.00% in STG (p=0.034). Furthermore, there was no statistically significant difference in relapse rates and adverse events between the two groups. CONCLUSIONS: Individualized combination therapy can achieve higher antiviral response rates. In particular, it can accelerate undetectable HBV DNA and elevate HBeAg clearance/seroconversion rates to a greater degree than Peg-IFNa-2a monotherapy.

[Identification of the meiotic events in grasshopper spermatogenesis].

The grasshoppers are ideal materials to study various meiotic stages of spermatogenesis due to their easy availability, fairly large chromosomes, and fewer numbers of chromosomes. It is easy to make temporary squash preparation of grasshopper testes; however, it is usually difficult for the beginners to differentiate between stages of meiosis. In view of this, we demonstrated the method of identification of meiotic stages by chromosome number and chromosome conformation, taking spermatogonial meiosis of Locusta migratoria manilensis as an example. We described briefly the mitosis of spermatogonia and the spermatogenesis of this species as well.

[A clinical study of pituitrin versus norepinephrine in the treatment of patients with septic shock].

OBJECTIVE: To investigate whether pituitrin can lower 28-day mortality as compared with treatment with norepinephrine (NE) in patients with septic shock. METHODS: Randomized, controlled, open-label trial was conducted. One hundred and thirty-nine septic shock patients with dopamine requirements exceeding 5 µg×kg(-1)×min(-1) were divided at random into two groups as the study group and control group. All patients enrolled were treated by the same treatment principle and measures. In patients of study group injection of pituitrin 0.017-0.042 U/min (1.0- 2.5 U/h) was given, and if hemodynamics was still unstable, catecholamines was added to obtain the target blood pressure; while in the control group catecholamines was given to maintain stability of hemodynamics. RESULTS: Among 139 patients enrolled in the study, 66 composed of the clinical study group and 73 in the control group. The main principle of the treatment in the two groups was similar. There was no significant difference in overall 28-day mortality rate between study group and control group (40.9% vs. 46.6%, P > 0.05). In patients whose acute physiology and chronic health evaluation II ( APACHE II ) score was less than 25, the mortality of study group was significantly lower than that of control group [10.3% (3/29) vs. 35.7% (10/28), P < 0.05]. The length of stay in intensive care unit [ICU, days: 5(3,8) vs. 5(3,8)], and duration of mechanical ventilation [days: 4.0 (2.8, 6.0) vs. 4.0 (2.0, 5.0)] were similar in two groups (both P > 0.05). The dosage of NE (µg/min: 7.99 ± 5.02 vs. 10.12 ± 5.12) and heart rate (beat/min: 93.27 ± 7.84 vs. 108.45 ± 12.31) were significantly lower in study group compared with that of control group (both P < 0.05). Serum creatinine and lactate levels in the two groups were similar at baseline, and creatinine [µmol/L: 87.5 (62.8, 157.0) vs. 76.0 (52.5, 117.0)] and lactate level (mmol/L: 3.72 ± 2.47 vs. 3.53 ± 1.86) were still similar in two groups 24 hours later (all P > 0.05). The rate of use of glucocorticoid (43.9% vs. 31.5%) and heparin in small dosage (42.4% vs. 41.1%) had no significant difference between two groups (both P > 0.05). CONCLUSIONS: Combined use of pituitrin in patients with septic shock can reduce the dosage of catecholamines, and decrease the heart rate. Although it can not lower the overall mortality of septic shock, among patients with less severity whose APACHE II score lower than 25, low-dose pituitrin in conjunction with catecholamine vasopressors can reduce 28-day mortality .

Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury.

Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair. However, the underlying molecular mechanism remains unclear. In this study, we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation. Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype, inhibited the expression of proinflammatory cytokines, and increased the expression of anti-inflammatory cytokines. Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury, inhibited neuroinflammation, and promoted the transformation of microglia to the anti-inflammatory phenotype. We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process. Finally, we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection. We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype. The interleukin 10/STAT3 pathway was activated during this process. These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.