Along with the spread of human immunodeficiency virus 1 (HIV-1) infection in the world and the emergence of drug-resistant viral strains, it is urgent to seek the novel potent therapies. Chemokine receptor 5 (CCR5) is one of the main coreceptors involved in the entry of HIV-1 into target cells. Nowadays, a number of CCR5 antagonists have been developed and some of them have progressed to clinical trials or been approved. Research progress has also been made in the CCR5-targeted gene therapy. This review summarizes the recent research progress on the CCR5-targeted drug and gene therapy.
CCR5 Receptor Antagonists ; HIV Infections ; drug therapy ; genetics ; metabolism ; pathology ; HIV-1 ; drug effects ; Humans ; Molecular Targeted Therapy ; methods ; Receptors, CCR5 ; deficiency ; genetics ; metabolism

Objective To investigate the value of CT perfusion imaging in quantitative monitoring on microcirculation hemodynamics,differences between tumor and normal tissues,differences between mass center and edge,and on tumour microvascular responses to anti-angiogenesis therapy. Methods Fifteen male New Zealand white rabbits were established to VX2 tumor-bearing model. The animals were divided into 2 groups,anti-angiogenesis therapy (n=11,TNP-470,20 to 30 mg/kg),and control (n=4). DEC-CT scanning (80 kV,120 mA,20 cm VOF) was performed at 1 week after tumor implantation,1 week after anti-angiogenesis therapy,and 2 week after anti-angiogenesis therapy. Perfusion parameters,including blood flow (BF),blood volume (BV),mean transit time (MTT),and permeability surface (PS) were calculated for tumor mass,tumor edge,tumor center and normal tissue. Results Significant differences of the average values were observed in BF,PS and MTT between tumor and normal tissue [149.32?30.99 vs 32.18?4.10 ml/(100 g?min),28.24?5.15 vs 11.88?0.71 ml/(100 g?min),2.79?0.66 vs 6.57?0.90 s,P

Objective To evaluate the prognostic value of fluorodeoxyglucose (FDG) standardized uptake value (SUV) of positron emission tomography (PET) before radiotherapy in non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3DCRT). Methods Seventy-three patients with stage Ⅲ NSCLC underwent PET to calculate SUV within 2 weeks before 3DCRT. The a-nalysis was carried out after the irradiation of 60 -66 Gy. The possible prognostic factors were assessed by Cox proportional hazards model. Results The mean SUV for squamous cell carcinoma, adenocarcinoma and others were 16.94, 14.40 and 6.33, respectively (F = 0. 51, P = 0. 604). The mean SUV for tumor volume less than and more than 50 cm~3 was 13.81 and 20.18 (F = 7.54, P = 0. 008). In the univariate analysis, a cutoff SUV of 17 and chemotherapy were correlated with the prognosis. In the multivariate analysis, SUV was the only independent prognostic factor (relative risk = 2.61). Conclusions SUV is a prognostic factor in patients with NSCLC treated by 3DCRT, which deserves further studies.

The battlefield rescuing unit of the current model is always restricted by some factors such as regional environments in wartime rescuing action and peacetime disaster relief, which can lead to failure of following and deploying action, so that wounded persons can not be rescued at the first time. Aiming at the special circumstances, a forward first-aid unit composed of five doctors and nurses should be established to give emergency medical rescue with rescuing emergent equipments and medicine packed in portable packages such as portable respiring machine, defibrillator and oxygen device at the battlefront. In this way, success rate of rescuing wounded persons would be increased obviously, while mortality rate and deformity rate would be decreased greatly.

Objective To analyze results of bacterial infection distribution and drug sensitivity monitoring in 414 patients with open extremity injuries caused by Wenchuan earthquake so as to provide advices for guiding utility of antibiotics in treatment of patients injured in natural disasters. Methods Bacterial culture of wound secretion substance and drug sensitivity monitoring were done in 414 patients with open extremity injuries. Results There were 12 patients (2.9%) with G+ coccobacteria, 66 (15.9%) with G- bacillus, 2 (0.5%)with G+ bacillus, 6 (1.5%) with multiplicitas infection(5 with dual infection and I with triplication infection). Main pathogenic bacteria were as follows: (1)G+cocco- bacteria including Staphylococcus epidermidis, Staphylococcus aureus and anthropo-staphylococci ; (2) G- bacillus including Aerobacter cloacae, banmanii, escherichia co]i, aerugo pseudomonas, proteusvul- gaffs and Ewingella americana. (3)G+ bacillus including bacillus subtilis. The drugs with high sensi0tivi- ty to G+ coccobacteria included vancomycin, rifampin, levofloxacin and cidomycin, but those with low sensitivity to G+coccobacteria included penicillin, ampicillin and erythremycin. The drugs with high sen- sitivity to G- bacillus included imipenem, amikacin, levofloxaciu and tenebrimycin, but those with low sensitivity to G-bacillus included ampicillin and piperacillin. Conclusions Patients with open ex- tremity injuries caused by earthquake have rather high bacterial infection rate, involving many kinds of in- fection strains. Therefore, we should do bacterial culture and drug sensitivity monitoring of wound excre- tion substance as early as possible to guide rational use of antibiotics.

Objective To explore the mechanisms and effects of adoptive immunotherapy with ovarian cancer vaccine modified by GM-CSF gene which was used after immunologic reconstitution during lymphopenia induced by chemotherapy.Methods Lymphopenia was induced by chemotherapy with cyclophosphamide.The immune reconstituted model was built in rats.The tumor vaccine draining lymph nodes were harvested after the ovarian cancer cells NUTU-19 modified by GM-CSF gene were injected.The effector T cells (T_E) were got after being stimulated and amplified.Enzyme-linked immunosorbent assay was used to detect the level of interleukin (IL)-2 and IL-4 secreted by T_E.Intracellular cytokine staining was used to determine frequency of tumor-specific T_E.Fluorescence-activated cell sorting (FACS) was used to detect the special cytotoxicity ofT_E killing target cells.The survival period of rats bearing pre-established abdominal ovariam carcinoma after being adoptively transferred byT_E.was observed.Results Compared with those in control group,the significant higher levels IL-2[(65.7±4.0) pg/ml]and lower levels IL-4 [(277±49) pg/ml]were observed in chemotherapy-immune recunstitution-vaccine immunization group.The amount of CD_4~+ T cells secreting interferon-γ (13.0±2.1)% were also significantly increased.The rate of the special cytotoxicity of killing T cells (86.5±1.1) % was markedly improved.The survival period of rats (110±16) days was increased in chemotherapy-immune reconstitution-vaccine immunization group.Conclusions The combined immunotherapy of chemotherapy-immune reconstitution-tumor vaccine immunotherapy may increase the frequency and function of specific tumor T_E.The specific cytotoxicity is increased and the weak reaction of T_E to tumor is improved,which showed that this therapy can enhance immune reaction.

In the present study, we used in vitro whole-cell patch-clamp technique to record and analyze oscillatory activity of neurons in the optic tectum of Xenopus. Two patterns of subthreshold oscillations were induced by long-term depolarizing current pulses. One of the oscillating patterns occurred without a slow inward current (SIC); the other was superimposed on the SIC. The subthreshold oscillations were induced by depolarization in 48% of the recorded neurons. Both the oscillations and the SIC were tetrodotoxin (TTX)-resistant, but neither occurred when the slices were immersed in Ca(2+) free solutions. The evocation of the oscillations was voltage-sensitive: only when the initial membrane potentials of the neurons were held at -40 mV or -50 mV, 10 mV depolarization could induce the subthreshold oscillations. The amplitude and duration of the SIC depended on the level of the initial membrane potential. The subthreshold oscillations might play an important role in the physiological and behavioral functions of frogs, e.g. pattern discrimination, prey recognition, avoiding behavior etc., furthermore, these oscillations might play roles in the integration of neural activity in both mammals and non-mammalian vertebrates.
Animals ; Cell Polarity ; Membrane Potentials ; Neurons ; cytology ; Patch-Clamp Techniques ; Tetrodotoxin ; pharmacology ; Xenopus

IgA nephropathy is the most common form of primary glomerulonephritis which mainly accounts for the development of end-stage renal diseases. It is characterized by deposits of IgA1 in mesangium. The pathogenesis of IgA nephropathy is complicated. Moreover, there is a wide range of clinical features and variable histomorphologies in the diagnosed cases of IgA nephropathy. It was demonstrated that the galactose-deficient of IgA1 O-glycan chains led IgA1 to self-aggregation and eventual deposition in mesangium. Abnormality of glycosyltransferases, genetic mutation and immunologic disorder were involved in the aberrant glycosylation of IgA1 which was recognized as the key etiopathogenisis of IgA nephropathy. However, the exact source and the pathogenic mechanism of aberrantly glycosylated IgA1 remain obscure. The further studies on aberrant O-glycosylation of IgA1 would contribute to the understanding of IgA nephropathy and provide new therapeutical strategy.
Animals ; Glomerulonephritis, IGA ; etiology ; metabolism ; Glycosylation ; Humans ; Immunoglobulin A ; metabolism

Objective To analyze injury characteristics and treatment of hospitalized patients wounded in Wenehuan earthquake so as to provide references for medical rescue in disasters. Methods The study involved data of seismic patients from Trauma Database System Version 3.0 that collected clini-cal data of seismic patients admitted into West China Hospital of Sichuan University, Chengdu, and First and Second Hospitals of Deyang City. Trauma Database System Version 3.0 was developed by Research Institute for Traffic Medicine of PLA, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing. A comparative analysis was done on patient distribution, injury severity and medical treatment. Results There were 826 qualified patients including 410 males and 416 females ( at age range of 1-102 years, mean 45.8 years). Of all, the patients at age of 31-60 years accounted for 50. 2%. The patients were mainly peasants (43.8%, 208/477), workers (15.7%, 75/477) and students (14.1%, 67/477). Blunt injury (53.2%), crush/bury injury (22.5%) and slip/fall injury were three main causes for injury. The patients for 92.1% were admitted into two hospitals of the City of Deyang within four days after earthquake, while 81.7% of patients were admitted into West China Hospital in Chengdu at days 3-9 after earthquake. Patients with bone injuries accounted for 75.3%. The patients had abbreviated injury score (AIS) for mainly 1-3 points, with incidence rate of se-vere multiple trauma ( ISS > 16 points) of 8.2%. Internal fixation was done in 120 patients ( 34. 1% ), debridement and suturing in 103 (29.3%), external fixation in 55 ( 15.6% ), extremity amputation in 22 (6.3%) and intracerebral surgery in 2 (0.6%). Conclusions The injuries are mainly induced by collapse of buildings during earthquake. Bone injuries are predominant injury type, with AIS of mainly 1-3 points and few severe multiple trauma. The results show that the patients receive late special treat-ment and slow evacuation, indieating necessity of strengthening capacity of early medical treatment and ef-fective evacuation during destructive natural disasters.

OBJECTIVETo investigate the change of T lymphocyte subsets, interleukin (IL)-2 and tumor necrosis factor (TNF)-alpha in the tumor- bearing mice and patients with oral cancer receiving thermo-chemotherapy, and investigate the correlation among them.

METHODSAfter treatments, the expression of lymphocyte transformation index (LTI), IL-2 and TNF-alpha in the tumor-bearing mice were detected with methyl thiazolyl tetrazolium (MTT), the expression of IL-2 and TNF-alpha in the patients with oral cancer were detected with MTT, the expression of LTI, CD4+ and CD8+ were detected with 3H-TdR incorporation.

RESULTSLTI, IL-2 and TNF-alpha of thermo-chemotherapy group (HP group) had no significant difference comparing with those of normal mice group (N group) (P>0.05), but which were significantly higher than those of chemotherapy group (P group) and no treatment group (NT group) (P<0.01). In clinical trials, the expression of LTI, CD4+, CD4+/CD8+, IL-2 and TNF-alpha on oral cancer patients after thermo-chemotherapy were significantly higher than those before thermo-chemotherapy (P<0.01).

CONCLUSIONAfter thermo-chemotherapy, the expression of LTI, IL-2 and TNF-alpha of tumor-bearing hosts are significantly improved, there is a significant correlation between IL-2 and T cell.