Autologous bone marrow infusion via portal vein combined with splenectomy for decompensated liver cirrhosis: A retrospective study.

BACKGROUND: In a previous study, autologous bone marrow infusion (ABMI) was performed in patients with decompensated liver cirrhosis (DLC) and acquired immunodeficiency syndrome and achieved good results, but whether splenectomy affected outcome was unclear. AIM: To investigate the efficacy of ABMI combined with splenectomy for treatment of DLC. METHODS: Eighty-three patients with DLC were divided into an intervention group (43 cases) and control group (40 cases) according to whether splenectomy was performed. The control group was treated with ABMI through the right omental vein, and the intervention group was additionally treated with splenectomy. RESULTS: After ABMI, the prothrombin time, serum total bilirubin levels, ascites volume and model for end-stage liver disease score in both groups were significantly lower, while the albumin levels were significantly higher than before ABMI (P < 0.01), but there were no significant differences between the groups (P > 0.05). After ABMI, the white blood cell and platelets counts in both groups were significantly higher than before ABMI (P < 0.01), and the counts in the intervention group were significantly higher than in the control group (P < 0.01). After ABMI the CD4+ and CD8+ T cell counts in both groups were significantly higher than before ABMI (P < 0.01). The CD8+ T cell counts in the intervention group increased continuously and the increase had a shorter duration compared with control group. CONCLUSION: ABMI through the portal vein in patients with DLC can significantly improve liver synthetic and secretory functions, and splenectomy promotes improvement of bone marrow hematopoietic and cellular immune functions.

Variations in mitochondrial tRNA(Thr) gene may not be associated with coronary heart disease.

Mutations in mitochondrial tRNAThr gene were recently reported to be associated with coronary heart disease. These mutations, such as T15889C, G15927A, G15930A and A15951G, were claimed to be pathogenic. To examine whether these mutations contributed to the genetic susceptibility to coronary heart disease, we analyzed the conservation index of these mutations between different species. In particular, reports concerning the role of the G15927A mutation was the most controversial. Therefore, based on the previous and this study, we conducted that mutations in mitochondrial tRNAThr gene may not be associated with coronary heart disease.

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans-Infection of CD4+ T Cells.

UNLABELLED: The gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4ß7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4(+) T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viral trans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection. IMPORTANCE: In this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1 trans-infection of CD4(+) T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination.

[Proteomic analysis of peripheral blood mononuclear cells to identify potential markers of fibrosis in chronic hepatitis B].

OBJECTIVE: To identify non-invasive biomarkers for diagnosis and/or prognosis of liver fibrosis in chronic hepatitis B (CHB). METHODS: Peripheral blood samples were obtained from 48 patients with CHB, including 24 with mild fibrosis (stage 1, S1) and 24 with severe fibrosis (stage 4, S4), and subjected to Ficoll density gradient centrifugation in order to obtain enriched samples of peripheral blood mononuclear cells (PBMCs).The PBMC proteomes of the two groups were assessed by first separating the total proteins by two-dimensional gel electrophoresis (2DE) and then identifying the differentially expressed proteins by liquid chromatography combined with tandem mass spectrometry (LCMS/MS). RESULTS: The enriched PBMC samples from the S1 group and the S4 group had similar amounts of platelets [(19.268+/- 6.413) * 109/L and(19.480+/- 6.538) * 109/L, respectively); however, for both, the platelet amounts were 5 to 15-fold lower than that of the normal reference (100-300 *109/L). There was no significant difference found between the platelet amounts in the S1 patients and healthy controls (P=0.930). Twelve differentially expressed proteins were identified through 2DE-LC-MS/MS, including proteins such as moesin and NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 that are involved in various biological processes like cell movement, cell adhesion, kinase signaling and transcription. CONCLUSION: s The 12 proteins with differential expression in S1 and S4 patients with CHB and liver fibrosis may represent markers related to development and/or progression of liver fibrosis.

Treatment of postoperative infectious complications in patients with human immunodeficiency virus infection.

BACKGROUND: Antibiotics are widely given for surgical patients to prevent infection. Because of the lack of study on the rational use of antibiotics in patients with human immunodeficiency virus (HIV) -infected during surgical procedures, we analyzed the risk factors affecting postoperative infectious complications in HlV-infected patients and explore the rational use of perioperative antibiotics. METHODS: This retrospective study consisted of 308 HlV-infected patients, 272 males and 36 females, who had undergone operation at the Shanghai Public Health Clinical Center from November 2008 to April 2012. The patients were divided into postoperative infection and non-infection groups. Their age and clinical variables were compared. The correlation between surgical incision, surgical site infection (SSI) and postoperative sepsis was analyzed. Prophylactic antibiotics were used for patients with type I and II incisions for less than 2 days. Patients with type III incisions were given antibiotics until the infection was controlled. Antiretroviral therapy (ART) was prescribed preoperatively for patients whose preoperative CD4 count was <350 cells/µL. For those patients whose preoperative CD4 count was <200 cells/µL, sulfamethoxazole and fluconazole were given preoperatively as prophylactic agents controlling Pneumocystis carinii pneumonia and fungal infection. RESULTS: A total of 196 patients developed postoperative infectious complications, and 7 patients died. Preoperative CD4 counts, ratio of CD4/CD8 cells, hemoglobin level, and postoperative CD4 counts, hemoglobin and albumin levels were risk factors of perioperative infection in HIV-infected patients. Patients with a preoperative CD4 count <200 cell/µL, anemia, a postoperative CD4 count <200 cell/µL or albumin levels <35 g/L were correlated with a higher rate of perioperative infection. There was a significant correlation between SSI and the type of surgical incision. The rate of SSI in patients with type I surgical incision was 2% and in those with type II surgical incision was 38%. All the patients who received type III surgical incision developed SSI, and they were more likely to develop postoperative sepsis. CONCLUSIONS: HIV-infected patients are more likely to develop postoperative infectious complications. The rational use of antibiotics in HIV-infected patients could help to reduce the rate of postoperative infectious complications in these patients.

Polymorphism of A133S and promoter hypermethylation in Ras association domain family 1A gene (RASSF1A) is associated with risk of esophageal and gastric cardia cancers in Chinese population from high incidence area in northern China.

BACKGROUND: The role of tumor suppressor gene RASSF1A in the esophageal and gastric cardia carcinogenesis is still inconclusive. In this study, the polymorphism, promoter methylation and gene expression of RASSF1A were characterized in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). METHODS: We firstly analyzed the prevalence of RASSF1A A133S in a total of 228 cancer patients with ESCC (n=112) and GCA (n=116) and 235 normal controls by polymerase chain reaction (PCR) and restriction enzyme-digestion assay. Then, the promoter methylation status of the RASSF1A in ESCC (n=143), GCA (n=92) and corresponding adjacent normal tissues were further investigated using methylation-specific PCR (MSP) approach. Finally, the RASSF1A protein expression were determined in ESCC (n=27), GCA (n=24) and the matched adjacent normal tissues by immunohistochemical method. RESULTS: The frequency of 133Ala/Se and Ser/Ser genotype was significantly higher in GCA patients than in normal controls (19.0% vs. 10.2%, P=0.02). Compared with Ala/Ala genotype, Ala/Se and Ser/Ser genotype significantly increased susceptibility to GCA (OR=2.06, 95% CI=1.09-3.97). However, this polymorphism had no association with ESCC (P=0.69). The promoter methylation of RASSF1A gene was significantly increased the risk to both ESCC (OR=5.90, 95% CI=2.78-12.52) and GCA (OR=7.50, 95% CI= 2.78-20.23). Promoter methylation of RASSF1A gene in ESCC was also associated with age and cancer cell differentiation (for age: OR=3.11, 95% CI=1.10-8.73; for differentiation: OR=0.29, 95% CI=0.12-0.69). RASSF1A positive expression was significantly decreased the risk of GCA (OR=0.16, 95% CI=0.03-0.83). In contrast, there was no statistical significance between RASSF1A positive expression and ESCC. The expression of RASSF1A protein trend to be positively related with older GCA patients (OR=16.20, 95% CI=1.57-167.74). CONCLUSIONS: The present findings suggest that alterations of RASSF1A may play an important role in gastric cardia carcinogenesis in terms of polymorphism, promoter hypermethylation and protein expression. Whereas, RASSF1A hypermethylation may probably also be involved in esophageal squamous cell carcinogenesis.

Prevention and treatment of surgical site infection in HIV-infected patients.

BACKGROUND: Surgical site infection (SSI) are the third most frequently reported nosocomial infection, and the most common on surgical wards. HIV-infected patients may increase the possibility of developing SSI after surgery. There are few reported date on incidence and the preventive measures of SSI in HIV-infected patients. This study was to determine the incidence and the associated risk factors for SSI in HIV-infected patients. And we also explored the preventive measures. METHODS: A retrospective study of SSI was conducted in 242 HIV-infected patients including 17 patients who combined with hemophilia from October 2008 to September 2011 in Shanghai Public Health Clinical Center. SSI were classified according to Centers for Disease Control and Prevention (CDC) criteria and identified by bedside surveillance and post-discharge follow-up. Data were analyzed using SPSS 16.0 statistical software (SPSS Inc., Chicago, IL). RESULTS: The SSI incidence rate was 47.5% (115 of 242); 38.4% incisional SSIs, 5.4% deep incisional SSIs and 3.7% organ/space SSIs. The SSI incidence rate was 37.9% in HIV-infected patients undergoing abdominal operation. Patients undergoing abdominal surgery with lower preoperative CD4 counts were more likely to develop SSIs. The incidence increased from 2.6% in clean wounds to 100% in dirty wounds. In the HIV-infected patients combined with hemophilia, the mean preoperative albumin and postoperative hemoglobin were found significantly lower than those in no-SSIs group (P<0.05). CONCLUSIONS: SSI is frequent in HIV-infected patients. And suitable perioperative management may decrease the SSIs incidence rate of HIV-infected patients.

Preoperative CD4 count or CD4/CD8 ratio as a useful indicator for postoperative sepsis in HIV-infected patients undergoing abdominal operations.

BACKGROUND: CD4 count or CD4/CD8 ratio has been found to be a valuable marker of disease progression in HIV and AIDS. Our objective was to evaluate preoperative CD4 count or CD4/CD8 ratio as a useful indicator for postoperative sepsis in HIV-infected patients undergoing abdominal operations. METHODS: Retrospective analysis of 35 HIV-infected patients (four females, 31 males) undergoing abdominal operations. All patients were divided into postoperative sepsis group (A) and non-sepsis group (B). Demographic and clinical information were entered into a database and included: type of surgical procedure, age, peripheral blood cells, plasma albumin, CD4 counts, and CD4/CD8 ratios. Furthermore, we stratified and compared the incidence of postoperative sepsis according to the preoperative CD4 counts with breakpoint value of 200 cells/µL and preoperative CD4/CD8 ratios with breakpoint value of 0.15. RESULTS: Overall postoperative sepsis morbidity in our study was 51.43% (18/35). In sepsis group, the mean preoperative and postoperative CD4 counts, CD4/CD8 ratios, and postoperative platelet count were found significantly lower, respectively, than those in non-sepsis group (P < 0.05). The incidence of postoperative sepsis in the patients with preoperative CD4 counts ≤ 200 cells/µL was markedly higher than those with CD4 counts > 200 cells/µL (83.3% versus 17.65%; P = 0.000). Likewise, the incidence of postoperative sepsis in the patients with preoperative CD4/CD8 ratios ≤ 0.15 was dramatically higher than those with CD4/CD8 ratios > 0.15 (90% versus 36%; P = 0.007). CONCLUSIONS: Our preliminary study showed that HIV-infected patients with preoperative CD4 count ≤ 200 cells/µL or CD4/CD8 ratio ≤ 0.15 had overall higher postoperative sepsis morbidity. Preoperative CD4 count or CD4/CD8 ratio may be used as a useful indicator for postoperative sepsis in HIV-infected patients undergoing abdominal operations.

Functional polymorphism in exon 5 and variant haplotype of the interleukin-1 receptor-associated kinase 1 gene are associated with susceptibility to and severity of sepsis in the Chinese population.

BACKGROUND: The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) is believed to play an important role in the pathogenesis of sepsis. Recent studies have suggested that the IRAK1 functional genetic variant could affect the severity of sepsis in Caucasians. In this report, we have investigated whether polymorphisms at the IRAK1 gene are associated with the susceptibility to and severity of sepsis among the Chinese population. METHODS: Haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database. They were genotyped in 255 patients with sepsis and 260 control subjects by PCR/restriction fragment length polymorphism (RFLP) analysis. The association between the selected htSNPs and the susceptibility to and severity of sepsis were estimated by Logistic regression with adjustments for age, sex, smoking, drinking, chronic disease status, Acute Physiology and Chronic Health Evaluation (APACHE) II score and primary diseases. RESULTS: rs1059702 was selected to represent the six linked htSNPs for IRAK1. Genotype frequencies of the htSNPs were in Hardy-Weinberg equilibrium for females, as were allele frequencies for both sex groups. Associations were observed in females between the htSNPs C/C genotype and increased susceptibility to sepsis (odds ratio (OR), 5.46; 95% confidence interval (CI), 1.12 - 26.67; P = 0.018), and such associations were also observed between the IRAK1 variant haplotype (CC/C-allele) and increased susceptibility to sepsis (OR, 1.68; 95% CI, 1.05 - 2.70; P = 0.031) when compared with the T/T + T/C genotype and the wild-type haplotype (TC + TT/T-allele). In the multiple organ dysfunction syndrome (MODS) subgroup, the variant haplotype was also associated with increased severity of sepsis (OR, 2.37; 95% CI, 1.13 - 4.94; P = 0.02) when compared with the wild haplotype. This association was not significant in male patients. CONCLUSIONS: The functional polymorphism in exon 5 and the variant haplotype of IRAK1 gene mediate susceptibility to and severity of sepsis. IRAK1 might be a genetic risk factor for the occurrence and development of sepsis in the Chinese population.

[Predictive value of immunological parameters on sepsis following abdominal operation for patients with HIV infection].

OBJECTIVE: To study postoperative sepsis in HIV/AIDS patients who underwent abdominal operations. METHODS: A retrospective analysis was performed to study 34 HIV/AIDS patients treated between January 2009 and December 2010 at the Shanghai Public Health Clinical Center Affiliated to Fudan University. RESULTS: There were 31 males and 3 females in this cohort with a mean age of 45±13 years. Nineteen patients developed postoperative sepsis. The levels of preoperative CD4, postoperative CD4, preoperative CD4/CD8, and postoperative platelet were significantly lower than those without sepsis (all P<0.05). Among 19 patients with a preoperative CD4 cell count less than or equal to 200×10(6)/L, the incidence of postoperative sepsis rate was 84.2%(16/19), and for those with a preoperative CD4 cell count greater than 200×10(6)/L, the incidence of postoperative sepsis rate was 20.0%(3/15), the difference was statistically significant(P<0.05). There were 3 postoperative deaths. CONCLUSION: CD4 cell count can be used as a predictive marker for the development of postoperative sepsis in patients with HIV/AIDS.

TRAF6 polymorphisms not associated with the susceptibility to and severity of sepsis in a Chinese population.

BACKGROUND: The tumor necrosis factor recepter associated factor (TRAF) 6 is an important intracellular adapter protein that plays a pivotal role in activating multiple inflammatory and immune related processes induced by cytokines. TRAF6 represents a strong candidate susceptibility factor for sepsis. We investigated whether polymorphisms at the TRAF6 gene are associated with the susceptibility to and severity of sepsis. METHODS: A hospital-based case-control study was conducted with 255 patients with sepsis and 260 controls who were recruited from Zhengzhou, China. Haplotype tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database and genotyped using the SNPstream genotyping platform. The associations with the susceptibility and disease severity of sepsis were estimated by logistic regression, and adjusted for age, sex, smoking, drinking, chronic diseases status, APACHEII score and critical illness status. RESULTS: A total of 13 TRAF6 SNPs were tagged by 7 htSNPs. Five htSNPs (rs5030490, rs5030411, rs5030416, rs5030445 and rs3740961) were genotyped in the case control study. Genotype frequencies of the htSNPs were conformed to the Hardy-Weinberg equilibrium in both patients and controls. No significant association was found between the 5 htSNPs and the susceptibility to and severity of sepsis. Compared with the main haplotype -11120A/-10688T/-9423A/805G/12967G, no certain haplotype was associated with the significantly susceptibility to or severity of sepsis. CONCLUSION: TRAF6 gene polymorphisms might not play a major role in mediating the susceptibility to and severity of sepsis in the Chinese population. A larger population-based case-control study is warranted.