Clinical observations of bone marrow transfusion for promoting bone marrow reconstruction after chemotherapy for AIDS-related lymphoma.

BACKGROUND: This study investigates the effect of autologous bone marrow transfusion (BMT) on the reconstruction of both bone marrow and the immune system in patients with AIDS-related lymphoma (ARL). METHODS: A total of 32 patients with ARL participated in this study. Among them, 16 participants were treated with conventional surgery and chemotherapy (control group) and the remaining 16 patients were treated with chemotherapy followed by autologous bone marrow transfusion via a mesenteric vein (8 patients, ABM-MVI group) or a peripheral vein (8 patients, ABM-PI group). Subsequently, peripheral blood and lymphocyte data subsets were detected and documented in all patients. RESULTS: Before chemotherapy, no significant difference in indicators was observed between three groups of ARL patients. Unexpectedly, 2 weeks after the end of 6 courses of chemotherapy, the ABM-MVI group, and the ABM-PI group yielded an increased level of CD8+T lymphocytes, white blood cells (WBC), and platelet (PLT) in peripheral blood in comparison to the control group. Notably, the number of CD4+T lymphocytes in the ABM-PI group was significantly higher than that in the other two groups. Additionally, no significant difference in haemoglobin levels was observed before and after chemotherapy in both the ABM-MVI and ABM-PI groups, while haemoglobin levels in the control group decreased significantly following chemotherapy. CONCLUSIONS: Autologous bone marrow transfusion after chemotherapy can promote the reconstruction of both bone marrow and the immune system. There was no significant difference in bone marrow recovery and reconstruction between the mesenteric vein transfusion group and the peripheral vein transfusion group.

Synthesis of Biotin-Modified Galactosylated Chitosan Nanoparticles and Their Characteristics in Vitro and in Vivo.

BACKGROUND/AIMS: Our previous study found that a nanoparticle drug delivery system that operates as a drug carrier and controlled release system not only improves the efficacy of the drugs but also reduces their side effects. However, this system could not efficiently target hepatoma cells. The aim of this study was to synthesize biotin-modified galactosylated chitosan nanoparticles (Bio-GC) and evaluate their characteristics in vitro and in vivo. METHODS: Bio-GC nanomaterials were synthesized, and confirmed by fourier transform infrared spectroscopy (FT-IR) and hydrogen-1 nuclear magnetic resonance (1H-NMR). The liver position and cancer target property of Bio-GC nanoparticles in vitro and in vivo was tested by confocal laser and small animal imaging system. The characteristics of Bio-GC/5-fluorouracil (5-FU) nanoparticles in vitro and in vivo were explored by cell proliferation, migration and cytotoxicity test, or by animal experiment. RESULTS: Bio-GC nanoparticles were synthesized with biodegradable chitosan as the nanomaterial skeleton with biotin and galactose grafts. Bio-GC was confirmed by FT-IR and 1H-NMR. Bio-GC/5-FU nanoparticles were synthesized according to the optimal mass ratio for Bio-GC/5-FU (1: 4) and had a mean particle size of 81.1 nm, zeta potential of +39.2 mV, and drug loading capacity of 8.98%. Bio-GC/5-FU nanoparticles had sustained release properties (rapid, steady, and slow release phases). Bio-GC nanoparticles targeted liver and liver cancer cell in vitro and in vivo, and this was confirmed by confocal laser scanning and small animal imaging system. Compared with GC/5-FU nanoparticles, Bio-GC/5-FU nanoparticles showed more specific cytotoxic activity in a dose- and time-dependent manner and a more obvious inhibitory effect on the migration of liver cancer cells. In addition, Bio-GC/5-FU nanoparticles significantly prolonged the survival time of mice in orthotopic liver cancer transplantation model compared with other 5-FU nanoparticles or 5-FU alone. Bio-GC (0.64%) nanomaterial had no obvious cytotoxic effects on cells; thus, the concentration of Bio-GC/5-FU nanoparticles used was only 0.04% and showed no toxic effects on the cells. CONCLUSION: Bio-GC is a liver- and cancer-targeting nanomaterial. Bio-GC/5-FU nanoparticles as drug carriers have stronger inhibitory effects on the proliferation and migration of liver cancer cells compared with 5-FU in vitro and in vivo.

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.

Preoperative risk factors influencing the incidence of postoperative sepsis in human immunodeficiency virus-infected patients: a retrospective cohort study.

BACKGROUND: Compared to noninfected patients, human immunodeficiency virus (HIV)-infected patients undergoing surgery have an increased postoperative risk of developing sepsis. We aimed to investigate the preoperative risk factors that affect the incidence of sepsis after surgery in HIV-infected patients. METHODS: Clinical parameters of 215 patients with HIV/acquired immunodeficiency syndrome (AIDS) who had undergone surgery between January 2011 and February 2012 were examined retrospectively for the effect of HIV/AIDS on the incidence of postoperative sepsis. RESULTS: Logistic regression analysis identified four independent risk factors of postoperative sepsis in HIV-infected patients: CD4 counts [B = -0.007, odds ratio (OR) 0.993]; blood albumin levels (B = -0.077, OR 0.926); surgical infection (B = 1.887, OR 6.598); major surgery (B = 1.013, OR 2.754). The incidence of postoperative sepsis was high with CD4 counts ≤ 100 cells/µl, albumin levels <35 g/L, the presence of surgical infection, the patient had undergone major surgery--81.25%, 39/48; 76.47%, 26/34; 70.73%, 29/41; and 54.76%, 46/84, respectively, compared to that of the total cohort (40.93%, 88/215). When CD4 counts were >350 cells/µl, the incidence of postoperative sepsis was significantly lower (16.36%, 9/55). CONCLUSIONS: Low CD4 cell counts, hypoalbuminemia, surgical infection, and major surgery are independent risk factors for the development of postoperative sepsis among HIV-infected patients. CD4 cell numbers and albumin levels negatively correlated with the incidence of postoperative sepsis, whereas surgical infections and major surgical procedures positively correlated with the incidence of postoperative sepsis.

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.

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.

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.

Anti-infective treatment in HIV-infected patients during perioperative period.

OBJECTIVE: To investigate anti-infective treatments in HIV-infected surgical patients during the perioperative period. METHODS: A retrospective study of sepsis and surgical site infections (SSIs) was conducted in 266 HIV-infected patients. The patients were divided into 3 groups based on CD4+ T cells counts in the preoperative period: group A (0-199 cell/ul), group B (200-349 cell/ul) and group C ([greater than or equal to] 350 cell/ul). When the CD4 count was below 350 cells/uL, anti-retrovirus therapy was started. For patients whose preoperative CD4 counts were [less than or equal to] 200 cells/uL, preoperative antibiotic medication was started. RESULTS: Patients in group A were more likely to get sepsis than patients in the other two groups (p0.01). Among 82 patients with clean wounds, only one patient got SSIs. All patients with dirty wounds had acquired SSIs after surgery. There were only 6 patients dead at 30 days after surgery, a death rate of 2.3%. Sepsis appeared in 110 patients (41%). CONCLUSIONS: Complete evaluation of surgical risk and suitable perioperative anti-infective treatment may lead to better outcome for HIV-infected surgical patients.

GANT61 exerts anticancer cell and anticancer stem cell capacity in colorectal cancer by blocking the Wnt/ß­catenin and Notch signalling pathways.

The present study aimed to assess the anticancer cell and anticancer stem cell (CSC) effects of GANT61, and its regulatory influence on the Wnt/ß­catenin and Notch signalling pathways in colorectal cancer (CRC). HT­29 and HCT­116 cells were treated with 0, 2.5, 5, 10, 20 or 40 µM GANT61, after which relative cell viability and the expression of Gli1, ß­catenin and Notch1, as well as the percentage of CD133+ cells, were detected. Subsequently, HT­29/HCT­116 cells and CSCs were treated with 20 µM GANT61, 10 mM of the Wnt/ß­catenin pathway agonist HLY78, and 30 mM of the Notch pathway agonist JAG1 (alone or in combination), which was followed by the assessment of cell viability and apoptosis. In both cell lines, GANT61 reduced relative cell viability in a time­ and dose­dependent manner, inhibited Gli1, ß­catenin and Notch1 expression, and decreased the percentage of CD133+ cells in a dose­dependent manner. Furthermore, HLY78 and JAG1 were both found to improve the relative viability, while downregulating the apoptosis of untreated and GANT61­treated HT­29 and HCT­116 cells. Moreover, Wnt/ß­catenin and Notch signalling pathway activity were upregulated in CSCs isolated from HT­29 and HCT­116 cells, compared with the associated control groups. GANT61 also reduced the viability of HT­29 and HCT­116 cells and increased apoptosis, whereas HLY78 and JAG1 treatment resulted in the opposite effect. Moreover, both HLY78 and JAG1 attenuated the effects of GANT61 on cellular viability and apoptosis. In conclusion, GANT61 was found to effectively eliminate cancer cells and CSCs by blocking the Wnt/ß­catenin and Notch signalling pathways in CRC.

Therapeutic effect of autologous bone marrow cells injected into the liver under the guidance of B­ultrasound in the treatment of HBV­related decompensated liver cirrhosis.

The 5-year mortality rates associated with decompensated liver cirrhosis (DLC) can reach 50%, which suggests that this condition poses a serious health risk. In previous studies conducted by our group, autologous bone marrow nucleated cells (ABMNCs) were used to treat HIV-positive patients with DLC through the right omental vein; however, trauma and poor compliance were encountered. In the present study, the percutaneous liver approach to inject ABMNCs under the guidance of B-ultrasound was employed for the treatment of DLC. A total of 108 patients with DLC were retrospectively divided into the routine drug treatment group (control group; 30 cases), the right omental vein infusion of ABMNCs group (observation group 1; 38 cases) and the B-ultrasound-guided liver injection of ABMNCs group (observation group 2; 40 cases). After treatment, the liver synthesis (prothrombin time, albumin and ascites) and secretion functions (total bilirubin) in observation groups 1 and 2 were significantly improved compared with those of the control group (P<0.01) and the bone marrow function was also significantly improved compared with that of the control group (P<0.01). While, the bone marrow function (white blood cell, platelet, and hemoglobin) in observation group 1 was significantly improved compared with that of observation group 2 at the end of treatment (P<0.01). After a 1-year follow-up, the case fatality rate was 2.5% (1/40) in observation group 2, which was significantly lower than the 20% fatality rate (6/30) recorded in the control group (P<0.05). The injection of ABMNCs into the liver under the guidance of B-ultrasound was significantly better than conventional drug therapy in treating DLC. This approach has obvious advantages such as no hospitalization, minimal trauma, rapid recovery and good compliance, all of which make it worthy of application in primary hospitals.

Autologous Bone Marrow Cell Infusion for the Treatment of Decompensated Liver Cirrhosis Patients With Type 2 Diabetes Mellitus.

This study aimed to indicate whether autologous bone marrow cell infusion (ABMI) via the right omental vein (ROV) could have a regulatory effect on decompensated liver cirrhosis (DLC) patients with type 2 diabetes mellitus (T2DM). For this purpose, 24 DLC patients with T2DM were divided into observation group (n=14) and control group (n=10). Patients in the observation group were given ABMI through the ROV and right omental artery (ROA), and cases in the control group received ABMI through the ROV. At 1, 3, 6, and 12months after ABMI, it was revealed that the prothrombin time, the total bilirubin levels, and the amount of ascites were significantly lower, while the serum albumin levels in the two groups were markedly higher compared with those before ABMI (p<0.01), and there was no significant difference between the two groups at each time point (p>0.05). The fasting blood glucose and glycosylated hemoglobin levels at 6 and 12months after ABMI in the two groups significantly decreased compared with those before ABMI (p<0.05 or p<0.01), while the decreased levels in the observation group were more obvious than those in the control group at each time point (p<0.01). The amount of insulin in the observation group at 3, 6, and 12months after ABMI was significantly less than that before ABMI in the control group (p<0.01). In summary, ABMI showed a significant therapeutic efficacy for DLC patients with T2DM through ROV and ROA.

Autologous bone marrow cell transplantation in the treatment of HIV patients with compensated cirrhosis.

Liver stem cell therapy is a promising tool to improve decompensated liver cirrhosis (DLC). Especially in patients infected with human immunodeficiency virus (HIV), the condition of the liver may be aggravated by antiretroviral therapy. A total of 21 patients diagnosed with DLC and HIV infection were divided into two groups as follows: those who received (combination therapy group, 14 patients) and those who did not receive (routine therapy group, 7 patients) bone marrow cell transplantation through the portal vein. Two patients died of surgery-related complications in the combination therapy group. The results showed that the survival rate was 85.7% in the combination therapy group after 2 years of follow-up, which was significantly higher than the 14.3% in the conventional therapy group (P<0.01). After treatment, the liver function score decreased significantly in the combination therapy group at 1 (t = 4.276, P = 0.000), 3 (t = 9.153, P = 0.000), and 12 (t = 13.536, P = 0.000) months, the levels of albumin were significantly increased, and the total bilirubin level and prothrombin time were significantly reduced or shortened as compared with the routine therapy group (P<0.05 or <0.01). The white blood cell count, hemoglobin, platelet count, and CD4+ and CD8+ levels were significantly higher in the combination therapy group at different time points as compared with the routine therapy group (P<0.05 or <0.01). In summary, the combination therapy is effective in HIV-infected patients with DLC and useful for the recovery of liver function and cellular immune function but may increase the risk of severe complications after surgery.

Fibrotic liver microenvironment promotes Dll4 and SDF-1-dependent T-cell lineage development.

The reconstitution of the T-cell repertoire and quantity is a major challenge in the clinical management of HIV infection/AIDS, cancer, and aging-associated diseases. We previously showed that autologous bone marrow transfusion (BMT) via the hepatic portal vein could effectively restore CD4+ T-cell count in AIDS patients also suffering from decompensated liver cirrhosis. In the current study, we characterized T-cell reconstitution in a mouse model of liver fibrosis induced by CCl4 and found that T-cell reconstitution after BMT via hepatic portal vein was also greatly enhanced. The expression of Dll4 (Delta-like 4), which plays an important role in T-cell progenitor expansion, was elevated in hepatocytes of fibrotic livers when compared to normal livers. This upregulation of Dll4 expression was found to be induced by TNFα in an NFκB-dependent manner. Liver fibroblasts transfected with Dll4 (LF-Dll4) also gained the capacity to promote T-cell lineage development from hematopoietic stem cells (HSCs), resulting in the generation of DN2 (CD4 and CD8 DN 2) and DN3 T-cell progenitors in vitro, which underwent a normal maturation program when adoptively transferred into Rag-2 deficient hosts. We also demonstrated a pivotal role of SDF-1 produced by primary liver fibroblasts (primary LF) in T-lineage differentiation from HSCs. These results suggest that Dll4 and SDF-1 in fibrotic liver microenvironment could promote extrathymic T-cell lineage development. These results expand our knowledge of T-cell development and reconstitution under pathological conditions.

Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy.

OBJECTIVE: This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. METHODS: A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), α-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. RESULTS: Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P < 0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. CONCLUSIONS: Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.

Zinc-Finger Nucleases Induced by HIV-1 Tat Excise HIV-1 from the Host Genome in Infected and Latently Infected Cells.

Highly active anti-retroviral therapy (HAART) cannot clear infected cells harboring HIV-1 proviral DNA from HIV-1-infected patients. We previously demonstrated that zinc-finger nucleases (ZFNs) can specifically and efficiently excise HIV-1 proviral DNA from latently infected human T cells by targeting long terminal repeats (LTRs), a novel and alternative antiretroviral strategy for eradicating HIV-1 infection. To prevent unwanted off-target effects from constantly expressed ZFNs, in this study, we engineered the expression of ZFNs under the control of HIV-1 LTR, by which ZFN expression can be activated by the HIV-1 (Trans-Activator of Transcription) Tat protein. Our results show that functional expression of ZFNs induced by Tat excise the integrated proviral DNA of HIV-NL4-3-eGFP in approximately 30% of the population of HIV-1-infected cells. The results from HIV-1-infected human primary T cells and latently infected T cells treated with the inducible ZFNs further validated that proviral DNA can be excised. Taken together, positively regulated expression of ZFNs in the presence of HIV-1 Tat may provide a safer and novel implementation of genome-editing technology for eradicating HIV-1 proviral DNA from infected host cells.

Human immunodeficiency virus (HIV) is highly associated with giant idiopathic esophageal ulcers in acquired immunodeficiency syndrome (AIDS) patients.

OBJECTIVE: This study aimed to determine whether the human immunodeficiency virus (HIV) exists in giant idiopathic esophageal ulcers in the patients with acquired immune deficiency syndrome (AIDS). METHODS: 16 AIDS patients with a primary complaint of epigastric discomfort were examined by gastroscopy. Multiple and giant esophageal ulcers were biopsied and analyzed with pathology staining and reverse transcription-polymerase chain reaction (RT-PCR) to determine the potential pathogenic microorganisms, including HIV, cytomegalovirus (CMV) and herpes simplex viruses (HSV). RESULTS: HIV was detected in ulcer samples from 12 out of these 16 patients. Ulcers in 2 patients were infected with CMV and ulcers in another 2 patients were found HSV positive. No obvious cancerous pathological changes were found in these multiple giant esophageal ulcer specimens. CONCLUSION: HIV may be one of the major causative agents of multiple benign giant esophageal ulcers in AIDS patients.

Sepsis risk factors associated with HIV-1 patients undergoing surgery.

Recent developments in the treatment of HIV-1 have improved the disease prognosis from a terminal disease to a chronic disease. The number of HIV-1-infected patients who require surgery has become more common. The main threat to HIV-1-infected patients following surgery is the development of sepsis. In this study, we collected a large number of clinical recordings of HIV-1-infected patients from two hospitals in China, specializing in HIV-1 treatment in order to summarize the risk indicators of sepsis in HIV-1-infected patients. We compared the significant risk indicators between the sepsis and non-sepsis groups. Using logistic regression based on the indicators of four separate surgery-based diseases, we generally found that low CD4 and hypoalbuminemia counts prior to surgery were the significant risk factors for developing sepsis. The morbidity of sepsis in trauma patients was approximately 10 times higher than the dysfunction group, whereas the tumor and the infection groups were approximately 1.5 and 2 times higher, respectively. Based on the comparison between the sepsis and non-sepsis groups for each surgery-based disease, we found that the severity of trauma is a critical risk factor for trauma patients; therefore, limiting the size of the wound during surgery is crucial. HIV-1-infected patients often develop postoperative sepsis due to immunodeficiency and complications due to the surgery. We hope that this study can help to reduce the risk of developing sepsis due to surgery and improve the survival rate of HIV-1-infected patients.

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.

Willingness to participate in HIV therapeutic vaccine trials among HIV-infected patients on ART in China.

BACKGROUND: More and more HIV therapeutic vaccines will enter clinical trials; however, little is known about the willingness to participate (WTP) in HIV therapeutic vaccine trials among HIV-positive individuals. OBJECTIVE: To investigate the WTP in HIV therapeutic vaccine trials among Chinese HIV-infected patients. METHODS: We conducted a cross-sectional survey on HIV-positive inpatients and outpatients at Shanghai Public Health Center. A total of 447 participants were recruited into this study. Following an introduction with general information on HIV therapeutic vaccine and its potential effectiveness and side effects, each participant completed a questionnaire in a self-administered form. The questionnaires covered demographics, high-risk behaviors, clinical characteristics and willingness to participate in HIV therapeutic vaccine trial. RESULTS: The overall willingness to participate in HIV therapeutic vaccine trials was 91.5%. Interestingly, multivariate logistic regression analyses demonstrated that the willingness was higher for those sexually infected by HIV (odds ratio [OR]: 4.36; 95% confidence interval [CI]: 1.53-12.41), diagnosed as HIV-1 infection for greater than 5 years (OR: 7.12, 95% CI: 1.83-27.76), and with the presence of infectious complications (OR: 2.75; 95% CI: 1.02-7.45). The primary reason for participation was to delay or reduce antiretroviral treatment (ART) and to avoid ART side effects (76.6%), and then followed by delaying disease progression (74.9%), increasing immune response to suppress opportunistic infections (57.7%) and preventing the development of drug resistance (37.1%). Reasons for unwillingness to participate mainly included concern for safety (37.0%), lack of knowledge on therapeutic vaccine (33.3%), and satisfaction with ART effectiveness (22.2%). CONCLUSIONS: The WTP in HIV therapeutic vaccine trials was high among HIV-infected Chinese patients. HIV+ subjects who acquired infection through sexual contact and who were diagnosed for more than 5 years may represent a good candidate population for enrollment in therapeutic vaccine trials.