Modulation of host immune status by cryptococcus co-infection during HIV-1 pathogenesis and its impact on CD+4 cell and cytokines environment.

BACKGROUND: Cryptococcus infection is the second most common opportunistic infection in HIV patients with an increased rate of morbidity and mortality. Altered immune system during HIV- Cryptococcus co-infection is yet to be explored by laboratory. This study evaluates pro- and the anti-inflammatory cytokines in HIV patients with Cryptococcus co-infection and correlate them with CD4+T cell counts as well as viral loads before the initiation of drug therapy. This information would enable to understand host immune modulation and cellular environment during co-infection and understand its impact on HIV pathogenesis. METHODOLOGY: The study comprised four categories of patients with cryptococcosis, HIV, HIV-cryptococcosis co-infected and asymptomatic Healthy volunteers. All the patients and healthy individuals were subjected to CD4+T cells count by FACS using monoclonal antibody cocktail CD4+T cell count (counts per mm3) which was counted using multiSET software on FACS caliber. The viral loads were counted in terms of viral RNA copy numbers which was estimated by real-time PCR using by Artus HIV-1 RG. The sensitivity of kit was >70 IU/ml. ELISA was performed for IL-12 p70, IL-12, IL-4, IL-10, IL-6, TNF-α and IFN-Y using commercially kits (BD Biosciences, USA). Significant variations were assayed by Student's t-test and P values ≤ 0.05 were considered statistically significant. RESULTS: Reduction in CD+4 cell counts was highly significant in HIV patients with or without cryptococcosis. CD4+T cell counts were inversely proportional to viral load. TNF-α levels were raised in cryptococcosis patients significantly higher than healthy individuals. TNF-α was more or less not dependent on viral load but it was more related to the cryptococcosis IL-12 levels were increased in patients with infection and was highest in the HIV infected group. Level of IL-4 was similar in healthy and patients with cryptococcosis but it was elevated in HIV-Crypto co-infected patients. HIV infected patients showed a significant increase in IL-4 level and it was elevated higher in co-infected patients. IL-10 and IL-6 were significantly higher in HIV patients. The fungal infection did not influence the levels of IL-10 in HIV group but IL-6 was low in fungal infected patients. CONCLUSION: There are very limited studies related to the immune modulation status of HIV co-infected with Cryptococcus before the initiation of any drug therapy. Such information might through in-depth light to understand the initial state of the immune environment which certainly would play a pivotal role in the outcome of the immune modulation.

Clinical significance of Bcl-6 expression in young DLBCL patients with Myc+ or Bcl-2+Myc+ / 肿瘤

Objective: To investigate the expression of Bcl-6 in newly diagnosed and young patients with diffuse large B cell lymphoma (DLBCL), and to further explore its clinical significance in young DLBCL patients with Myc positive expression (Myc+) or Bcl-2 and Myc positive expressions (Bcl-2+Myc+). Methods: Immunohistochemical (IHC) staining was used to detect the expressions of Bcl-6, Myc and Bcl-2 in 116 newly diagnosed and young patients with DLBCL, and the complete clinical and pathological data were collected. The relationship between the expression levels of Bcl-6 protein and the prognosis of young DLBCL patients with Myc+ and Bcl-2+Myc+ was retrospectively analyzed. Results: There was no significantly correlation between the expression of Bcl-6 alone and the prognosis of young DLBCL patients (P > 0.05). However, for the DLBCL patients with Myc+, the prognosis in Bcl-6 negative (Bcl-6–) group was worse than that in Bcl-6 positive (Bcl-6+) group (P < 0.05). Furthermore, the multivariate COX regression analysis showed that Bcl-6–Myc+ expression was a significant independent factor of adverse prognosis except for the international prognostic index (IPI) (P < 0.05). Meanwhile, the prognosis of DLBLC patients with Bcl-6–Bcl-2+Myc+ was significantly worse than that of the patients with Bcl-6+Bcl-2+Myc+ (P < 0.05). Conclusion: Bcl-6 negative expression can increase the risk of poor prognosis in young DLBCL patients with Myc+ or Bcl-2+Myc+.

Mechanisms of resistance to cancer immunotherapy / 中华微生物学和免疫学杂志

Cancer immunotherapy uses the host′s immune system to mobilize immune cells to rec-ognize and eventually eliminate cancer cells .At present, studies in terms of cancer immunotherapy mainly focus on programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4 ) antibody, chimeric antigen receptor T-cell immunotherapy (CAR-T), T cell receptor Immunotherapy (TCR-T), etc.Despite the fact that cancer immunotherapies elicit unprecedented durable responses in clinical therapy , they appear to be ineffective to some patients .In addition, some responders relapse and show resistance to immunotherapies even if their symptoms are re -lieved for a time .Resistance to cancer immunotherapy can be categorized into primary , adaptive and ac-quired, which can occur in every stage during the process of anti-tumor response.In this review, we discuss the known mechanisms of resistance and provide a rationale for the use of combination therapy to overcome resistance.

Effects of Astragalus Injection Combined with Salmeterol Propionate Powder Inhalation on Pulmonary Func-tion,Cytokines and Blood Rheology Indexes of COPD Patients / 中国药房

OBJECTIVE:To investigate the effects of Astragalus injection combined with Salmeterol propionate powder inhala-tion on pulmonary function,cytokines and blood rheology indexes of Chronic obsrnctine pulmonary disease (COPD) patients. METHODS:104 COPD patients were divided into observation group and control group according to the randorn number table meth-od,with 52 cases in each group. Control group was given routine symptomatic treatment+Salmeterol propionate powder inhalation 1 dose,bid;observation group was additionally given Astragalus injection 30 ml added into 5% Glucose injection 250 ml,ivgtt, qd,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. Clinical efficacy,pulmonary function indexes [forced expiratory volume in one second(FEV1),forced vital capacity(FVC),FEV1/FVC],CRP,cytokine [IL-6,IL-8,TNF-α] levels,blood rheology indexes (whole blood high-shear viscosity,whole blood low-shear viscosity,fibrinogen,hematokrit and plasma viscosity),and the occurrence of ADR were observed in 2 groups. RESULTS:The total effective rate of observation group (94.23%)was significantly higher than that of control group(75.00%);compared with before treatment,FEV1,FVC and FEV1/FVC of 2 groups were significantly increased after treatment,and those of observation group were significantly higher than those of control group;CRP,IL-6,IL-8 and TNF-α of 2 groups were significantly decreased,and those of observation group were signifi-cantly lower than those of control group. The whole blood high-shear viscosity,whole blood low-shear viscosity,fibrinogen,hema-tocrit and plasma viscosity of observation group were decreased significantly after treatment,and the observation group was signifi-cantly lower than the control group,with statistical significance(P<0.05). No significant ADR was found in 2 groups. CONCLU-SIONS:Astragalus injection combined with Salmeterol propionate powder inhalation is significantly effective for COPD,improves pulmonary function of patients,improves micro inflammatory state and decreases blood rheology indexes with good safety.

Clinical Observation of Edaravone Combined with Citicoline Sodium in the Treatment of Acute Cerebral Infarction / 中国药房

OBJECTIVE:To investigate the therapeutic efficacy of edaravone combined with citicoline sodium on acute cere-bral infarction and its effects on the levels of oxidative stress and inflammatory factors. METHODS:108 patients with acute cere-bral infarction were randomly divided into edaravone group(single group)and edaravone+citicoline sodium group(drug combina-tion group),with 54 cases in each group. Based on routine treatment,single group was given Edaravone injection 30 mg added in-to 100 ml 0.9% Sodium chloride injection intravenously,bid,used up within 30 min each time;drug combination group was addi-tionally given Citicoline sodium injection 0.5 g added into 250 ml 0.9% Sodium chloride injection intravenously,qd,on the basis of single group. Treatment course of 2 groups lasted for 2 weeks. NIHSS,HDS,Barthel index,oxidant stress indicator and inflam-matory factors were compared between 2 groups before and after treatment. RESULTS:After treatment,the effective rate of NI-HSS in drug combination group was 81.48%,which was significantly higher than single group(53.70%),with statistical signifi-cance (χ2=9.511,P=0.002). HDS score and Barthel index of 2 groups were significantly increased after treatment,especially in drug combination group,with statistical significance(P<0.05). Compared with before treatment,contents of MDA and ET-1 in 2 groups were decreased significantly,while SOD activity and NO content were increased significantly;the inflammatory cytokines IL-6,IL-8,IL-12 and IL-16,TNF-α were all decreased gradually,with statistical significance (P<0.05);the improvement of each indicator in drug combination group was more significant than single group,with statistical significance(P<0.05). CONCLU-SIONS:Edaravone combined with citicoline sodium show good therapeutic efficacy in the treatment of acute cerebral infarction, can decrease the levels of oxidative stress and inflammation and promote the recovery of the neurological function and the daily liv-ing ability.

Analysis on antimicrobial susceptibility of bacteria on Poloxamer 407 gel / 重庆医学

Objective To evaluate the antimicrobial susceptibility of bacteria cultured on a Poloxamer 407(P407) thermosensi-tive in-situ gel .Methods The modified Kirby Bauer(K-B) disc diffusion method was adopted to determine the drug susceptibility of 9 kinds of bacterium isolated on the P407 and the Mueller Hinton(MH)agar culture medium, at the same time the diffusion rates of different antibacterial drugs on the P407 and the MH agar culture medium were compared;the sodium dodecylsulfate polyacrylam-ide gel electrophoresis(SDS-PAGE) was adopted to analyze the outer membrane proteins (OMPs) expression of Pseudomonas aeruginosa on these two kinds of culture medium .Results In the antimicrobial susceptibility tests, the inhibition zones on the P407 gel were found to be generally smaller than those on the MH agar.The difference in the diffusion rates of the antibacterial drugs on these two kinds of culture medium had no statistically significant difference (P> 0.05);the OMPs expression of Pseudomonas aeruginosa was similar to its growth expression on the P407 culture medium ,but different from its expression on the MH agar .Con-clusion P407 as an excipient of bacteria culture medium can be used in the screening test of the biofilm antimicrobial susceptibility .

Morphological variations of Paris polyphylla var. yunnansensis in different population / 中国中药杂志

<p><b>OBJECTIVE</b>To study the morphological variations of Paris polyphylla var. yunnansensis in different population for genetic diversity and breeding.</p><p><b>METHOD</b>The characters of roots, stalks, leave and flowers were observed. The results were analyzed by DPS software.</p><p><b>RESULT AND CONCLUSION</b>P. polyphylla var. yunnansensis showed plenty genetic diversity, there existed obvious differences in morphological characters of different population. Principal components analysis showed that the number of calyces, petal, carpels, stamens is main factor,which causes the morphological variations in different population. Cluster analysis shows that 26 populations are incorporates in two types as 45.08 Euclidean distance. Leaf area index is distinct different in this two types.</p>

Experience about Application of Risk Management in High-alert Medications in Ward Area of Our Hospital / 中国药房

OBJECTIVE: To provide reference for the improvement of management quality of high-alert medications in ward area. METHODS: Risk management was used to estimate risk factor of commonly used high-alert medications in ward area. Then the homologous management measures were formulated based on potential risk. RESULTS: With enforcement of risk management, risk awareness of relevant responsible person was strengthened. They knew more knowledge about high-alert medications and its rate increased from 60% to 96%. The phenomena such as nonstandard storage and placement of drugs, unclear identification had never happened again. CONCLUSION: The application of risk management in high-alert medications contributes to improve anti-distress awareness of relevant responsible person, guarantee safety of drug use and enhance the quality of care.