Volume 90  ·   Issue 09  ·  2010

This issue publishes three articles on clinical research and basic clinical research related to AIDS. The results are all innovative, have certain practical value and scientific significance, and also reflect the current level of clinical research on AIDS in China to some extent. The editorial department entrusts me to comment on the advantages and disadvantages of these three articles, and talk about the experience of how to carry out clinical research and publish articles on AIDS.

The National Institutes of Health (NIH) distributes tens of billions of dollars every year to support clinical and basic medical research. Although these funds are mainly supplied to American universities, scientific research institutions, small factories and small enterprises, NIH also provides hundreds of millions of dollars every year to schools and scientific research institutions outside the United States, and this amount is gradually expanding.

Objective To summarize the characteristics of clinical manifestation, chest radiology and microbiology of Rhedococcus equi pneumonia among patients with AIDS. Methods Total 1908 AIDS patients who have therapy in Longtan hospital of Guang Xi province since May 2007 to Nov 2009, 15 patients (0.79%) who were co-infected with Rhodacoccus equi, and average age was 35± 13 years, we retrospectively reviewed clinical manifestations, chest radiology and microbiology of nine HIV-infected patients complicated with Rhodococcus equi pneumonia. Results 14 patients presented with pneumonia or lung abscess, the clinical manifestations included fever ( 100% ), cough and expectoration ( 93. 3% ),bellyache (26. 7% ), etc. And 5 patients Hb lower than 60 g/L, CD_4~+ T cell count was between (1 -51 ) ×10~6/L, average was (20 ± 16) × 10~6/L, Patients presented with consolidation of lung. X-ray, or CT of lung showed large patchy consolidation image, inanition, atelectasis in the lung. Rhodococcus equi could be cultured from sputum, blood, tissue obtained through lung puncture, broncho-alveolar lavage fluid, etc.Though susceptible antibiotics were used, the focus in the lung was absorbed slowly, All of 15 patients begin with HAART, after 33day to 2years follow up 4 patients die and alive patients have perfect immune-rebuilt.Conclusions Rhodacuccus equi infection, an unusual disease, can be seen in AIDS patients and can be cured only with long-term effective antibiotic.

Objective To investigate the features of B7-H1 expression on peripheral myeloid dendritic cells (mDCs) in patients with HIV infection and evaluate the correlations between B7-H1expression and disease progression. Methods Peripheral blood samples from 82 treatment-naive patients with HIV infection, 28 viral complete responders (CRs) under antiretroviral therapy (ART) and 14 healthy controls (HCs) were collected. Flow cytometry was applied to investigate the expression of B7-H1 on mDCs and CD4 cell counts. Plasma HIV-1 viral load was detected by bDNA. Results The frequency of B7-H1expression on mDCs were 14. 15%±2.63%, 3. 31% ±0.51% and 0.52%±0. 10% in AIDS patients,asymptomatic HIV infected individuals and HCs respectively. As compared with HCs, B7-H1 was significantly up-regulated on mDCs in HIV/AIDS patients. The order was as follows: AIDS patients >asymptomatic HIV infected individuals > HCs ( all P < 0. 05 ). Interestingly, the expression of B7-H1 on mDCs in long-term nonprogressors (LTNPs) was 3. 12% ±1.14%. And it was lower than that in typical progressors (TPs) [8. 12% ±1.37% (P=0.001)]. Moreover, the expression of B7-H1 was negatively correlated with CD4 cell counts and positively correlated with plasma viral load in these patients (r =-0.631, P <0.01 and r =0.482, P <0.01 respectively). The expression of B7-H1 on mDCs was significantly lower in ART complete responders than that in AIDS patients (6. 59% ± 1.43% vs 14. 15% ±2. 63% ) ( P <0. 01 ). Expression of B7-H1 on mDCs decreased markedly in patients whose CD4 cell counts greatly elevated after a successful antiretroviral treatment. Conclusion The expression of B7-H1 on mDCs is significantly up-regalated in HIV/AIDS patients. With a close correlation with disease status, it acts as a marker of disease progression.

Objective This study aimed to evolution of genotypic drug resistance prevalence in treatment-failing patients in Shenzhen. Methods Peripheral venous blood samples were collected from 41AIDS patients whom failing combination antiretroviral therapy, and were amplified by nested PCR; then the amplified fragments were sequenced and analyzed. Results Partial pol sequences of 38 samples were successfully amplified, and 3 samples have not found any mutations in their pol sequences. K103N, G190A,Y181C, K101P, M184V, D67N, K70R, T215Y and K219 were most common mutations. According to the genotypie analysis, 100% of the patients (35/35) showed high and intermediate level resistance to nevirapine(NVP) and efavirenz (EFV); above 50% of the patients showed high and intermediate level resistance to zidovudine( AZT), lamivudine (3TC), stavudine (D4T) and didanosine (DDI) ; only a few patients showed intermediate and low level drug resistance to protease inhibitors(PIs). Patients whom take D4T + DDI + NVP regimens were most common to appear drug mutation. Conclusions The high prevalence of drug resistance to NNRTIs and NRTIs among patients faling combination antiretroviral therapy in Shenzhen. That is the main reason for treatment failure in AIDS patients. Now most of mutations were detected against NNRTIs and NRTIs, only a few against Pls. Our finding suggested that a second-line antiretroviral therapy regimens is needed among the patients failing therapy and the bensted-Pls maybe are good choice.

Objective To apply diffusion tensor imaging (DTI) for investigating the correlation between leukoaraiosis (LA) lesion's fraction anisotropy (FA) as well as average diffusion coefficient (DCavg) and LA severity, so as to explore DTI changes in microstructure of white marrow with normal ordinary MRI and its correlation with cognitive function. Methods Sixty LA patients and 30 healthy elderly people accepted DTI examination to detect the value of DCavg and FA of LA lesion and normal white marrow. The Mini-Mental State Examination (MMSE) was used for assessing cognitive function. Results LA severity (0 grade to 3 grade)was positively associated with DCavg, i.e. the more severe was LA, the higher DCavg was(0. 66±0. 05 to 1.09±0. 06, P <0. 05) ; and it was negatively associated with FA, i.e.the more severe was LA, the lower FA was(0. 42±0. 04 to 0. 26±0. 03, P < 0. 05 ). Neuropsychology tests (Mini-Mental State Examination, MMSE ) had asignificant relationship with DCavg and FA of normal appearing white matter( NAWM ) in LA patients( P <0. 05 ), especially in anterior horn( Pearson Correlation Coefficient 0. 422, P < 0. 05 ) and in centrnm semiovale ( Pearson Correlation Coefficient - 0. 495, P <0. 01 ). Conclusions In DTI examination, DCavg and FA of LA displays characteristic changes.Therefore, DTI can detect the macrostructaral changes of white marrow with normal MRI and these changes are related to cognitive function.

Objective To evaluate the indication and safety of video assisted thoracic surgery (VATS) for chest tumors. Methods Data of 144 consecutive patients receiving VATS between January and November 2009 in Cancer hospital Chinese Academy of Medical Sciences were retrospectively reviewed.Results There was no conversion to open thoracotomy. Overall morbidity rate was 2. 08% (3/144) and mortality rate was 0. 69% (1/144). There were no significant differences for operative time, number of nodal dissection, morbidity rate, mortality rate, overall hospitalization and postoperative length of stay between VATS lobectomy group and open thoracotomy (OT) lobectomy group. Chest tube duration was shorter in the VATS lobectomy group than OT lobectomy group and more early-stage lung cancer patientswere found in VATS group. There were no significant differences for number of nodal dissection, chest tube duration, morbidity rate, mortality rate, and postoperative length of stay between VATS lung wedge resection group and OT lung wedge resection group. Operative time and overall hospitalization were shorter in the VATS wedge resection group than OT wedge resection group. Conclusion Morbidity and mortality rate of VATS were acceptable. VATS lobectomy can be used as an alternative surgical technique for early-stage lung cancer. For lung wedge resection, VATS was superior than OT.

Objective To investigate the effects of various factors upon subclinical chorioamnionitis (SCCAS) during pregnancy and delivery. Methods A total of 796 cases of pregnancy in full-term birth at our hospital from December 2006 to December 2008 were reviewed. The data of maternal age, gravidity,parity, gestational age, prenatal care, history of vaginitis, premature rupture of membranes, occupation,educational status and delivery mode were recorded. And then the relationship between one of them and chorioamniotis were analyzed by χ~2 test. Results The overall incidence of SCCAS was 39. 95% in full-term birth. The pregnant women, who had no prenatal care or no occupation, or had a history of vaginitis or premature rupture of membranes, were found to have a higher incidence (P <0. 05 or P <0. 01 ). However,there were no statistical significance ( P > 0. 05 ) between SCCAS and other seven factors, such as gravida age, gravidity, parity, gestational age, educational status, delivery mode and living conditions. Conclusion Women with full-term birth, even in the absence of symptoms, may have already suffered from acute or chronic chorioamnioitis. The incidence is associated with prenatal care, history of vaginifis and premature rupture of membranes.

Objective To investigate the status of simulation education of anesthesiology in China.Methods Five hundreds questionnaires were mailed to chairmen of department of anesthesiology in teaching hospitals in 29 provinces and autonomous regions in China. The retrieved questionnaires and data were processed and analyzed with statistics. Results Sixty one questionnaires were retrieved, and retrived rate is 12. 2%. The result indicated that the theory and knowledge of anesthesiology was adopted for the training of medical students and residents in 2% teaching hospitals, theory and knowledge of anesthesiology combined with problem-based learning discussion in 52% teaching hospitals, theory and knowledge of anesthesiology combined with problem-based learning discussion and simulation training in 46% teaching hospitals. The order of simulation devices possessed was as follows: Basic Life Support (BLS) (79. 6% ), training model for clinical anesthesia techniques (53. 1% ) and Advances Life Support (ALS) (51.0%). There were only six teaching hospitals utilized Human Patient Simulator for anesthesia training. The result of evaluation of simulation education showed that 91.2% anesthesiologists recognized it as applicable, 90. 1%anesthesiologists recognized it as medical ethic requirement and 86. 0% anesthesiologists recognized it as partly close to clinical situation. The degree of cognition of anesthesiologists to simulation education was ordered as follows: manipulation correcting ability (92. 6% ), procedure controllability ( 87.0% ), training adjustability ( 76. 0% ) and patients safety ( 68. 5% ). Conclusion The simulation education of anesthesiology in China is still in the preliminary period. The executive departments of education should enhance supports to the simulation education in both hard ware and in soft ware.

Objective To acquire information on the IVD (intervertebral disc) proteome and analyze the differences of identified proteins during IVD development and maturation by a shotgun proteomics approach so as to identify the global protein expression patterns of IVD tissues from fetus and adults.Methods A 24-week fetus, a 25- and a 30-year-old adult IVD samples were collected and SDS-PAGE,RP-HPLC MS/MS shotgun analyses were performed. Bioinformational analysis with International Protein Index (IPI) database and functional classification with Gene Ontology Annotation (GOA) database were used to evaluate the results. Results A total of 524 proteins were identified in fetal IVD sample while 181and 172 proteins were observed in 25 and 30-year-old samples respectively. Fotty-eight proteins existed in three samples while 84 proteins in the 25-years-old and 30-years-old samples but not in fetus. Only 174high-quality proteins existed in fetal sample while 20 high-quality proteins in 25-year-old and 30-year-old samples. The physico-chemical characteristics of identified proteins displayed similar trends in three samples. Conclusions This study represents the first presentation of a global proteomic map of fetal and adult IVD samples using shotgun technology. Substantial differences exist in number and variety of proteins between development and mature IVD. This contributes to our overall knowledge in of biochemical components, metabolic regulation and biological mechanics in IVD.

：Objective To investigatethe value of NMO-IgG in the diagnosis of neuromyelitis optica (NMO). Methods A total of 80patients with NMO, high-risk NMO (HR-NMO), multiple sclerosis(MS) ,clinical isolatedsyndrome (CIS) and other neurological diseases ( subacute combined degeneration,cerebralinfarction, intracranial hemorrhage and neurofibroma) were included in to the study. Thetiters of all patients' serum NMO-IgG were detected by indirect immunofluorence. ResultsThere were significant differences in NMO, HR-NMO MS, and CIS between patients with severeoptical neuritis, transverse myelitis, normal brain MRI scan, spinal-cord lesion > 3segments and serum NMO-IgG positive (P <0. 05). The level of serum NMO-IgG of NMO,HR-NMO was higher than that of MS, while the level of serum NMO-IgG of MS was slightlyhigher than that of CIS and other diseases. The sensitivity and specificity of NMO-IgGwere 82.6% versus 96. 2% in the diagnosis of NMO. Conclusion NMO-IgG is valuable fordiagnosing NMO and differentiating it from MS.

Objective To understand the variations of sensory gating P50 in naive schizophrenia during follow-up and the relations with positive and negative symptom scale (PANSS). Methods The data of auditory evoked potential P50 were recorded by USA Nicolet Brova instrument from 58 naive schizophrenia patients (Sch) and 108 normal controls (NC) at baseline, Months 1, 2 and 3 after treatment. And a simultaneous assessment of PANSS was made. Results ( 1 ) At baseline, as compared with NC, Sch group had a sensory gating deficit, reflected by a higher S2/S1 ( Cz: NC :0. 43 (0. 27, 0. 58) ; Sch: 0. 77 (0. 58,1.04); Z= -9.23, P<0. 01), lower S1-S2 (Cz: NC: 2.65(1.55, 4.79)μV; Sch: 0.92( -0.13,2.32)μV; Z= -6.01, P<0.01) and decreased more (1-S2/S1) (Cz: NC:0.57(0.43, 0.73); Sch:0. 23 ( - 0. 04, 0. 42) ; Z = - 10. 61, P < 0. 01 ). (2) During follow-up, Sch group still had a sensory gating deficit. Compared with NC, Sch group had a more elevated S2-P50 amplitude, higher S2/S1, lower S1-S2 and ( 1-S2/S1 ) at Cz, Fz and Pz brain sites (P <0. 05-0. 01 ), and no significantly differences with S2-P50 amplitude, S2/S1, S1 -S2 and ( 1-S2/S1 ) during follow-up ( P > 0. 05). At baseline, Sch group had a much lowered S1-P50 amplitude than NC group at Cz and Fz brain sites (Cz: Sch: 4. 1 μV ±2. 1 μV,NC: 5.6 μV ±3.3 μV, t= -1.47,P=0.001; Fz: Sch: 3.9 μV ±2. 1 μN, NC: 5.6 μN ±3.9 μN, t=-1.63, P = 0. 003 ). At Month 3, Sch group showed an improved S1-P50 amplitude to normal level at Cz brain site, but S1-P50 amplitude improved at Fz brain site but it was lower than NC group (Sch: 3.9 μV±1.9 μV, NC: 5.6 μV ± 3.9 μV, t = - 1.62, P = 0. 03). (3) At Month 3, Sch group showed a much lowered PANSS scale, positive symptom scale, negative symptom scale and general psychiatric symptoms scale than that at baseline (baseline: 138 ± 15, 33 ±7, 41 ±5, 65±8; Month 3 : 80±15, 17±4, 24 ±4,38±9 respectively, P <0. 01 ). Spearman correlation revealed that P50 was not correlated with PANSS at baseline ( P > 0. 05 ). After treatment S2/S1 and ( 1 - S2/S1 ) correlated with positive symptom scale and thought disorde and S1-S2 positively with thought disorder in schizophrenia (P < 0. 05 ). Conclusion Sensory gating deficit is closely related with thought disorder in naive schizophrenia. And it may be an important pathogenesis of naive schizophrenia. P50 sensory gating deficit is probably a diathesis marker in schizophrenia.

Objective To observe the postoperative residual non-functioning pituitary adenomas (PR-NFPAs) without postoperative radiotherapy and to analyze the natural history of PR-NFPAs' growth in order to provide a basis for selecting appropriate strategies of clinical treatment. Methods We evaluated the natural history of 20 patients with PR-NFPAs who did not receive postoperative radiotherapy and drug therapy. Through MRI images, the residual tumor volumes of those patients were serially measured. We further calculated the monthly growth rate and the tumor volume doubling time (TVDT) and analyzed the correlations between the patient age, gender, volume of residual tumor, cavernous sinus (CS) invasion and TVDT. Results All patients received observation alone. Among which, 17 adenomas increased in volume and 3 remained unchanged during a follow-up period of 7 months to 17 years ( mean 3.90 yr). The mean patient age was 41.8 years. As to 17 patients with tumor regrowth, the tumor volume at the beginning of MRI observation period was 4. 73 cm~3 and tumor volume at the last MRI observation was 16. 98 cm~3. During the mean 4-year follow-up period, the average monthly growth rate of PR-NFPAs was 7. 87% and the mean TVDT was 724 days. Such factors as patient age, gender, volume of residual tumor and CS invasion did not affect the TVDT of PR-NFPAs. Conclusion The tumor growth rate of PR-NFPAs is not significantly correlated with the patient gender, age, volume of residual tumor and CS invasion. In conjunctions with the volume of PR-NFPAs and the distance between residual adenoma and optic chiasm, we should take the TVDT into consideration and determine the appropriate and safe follow-up period.

Objective To detect the changes of expressions of Ⅱ type collagen and matrix metalloproteinases-7 ( MMP-7 ) of acetabular cartilage in early DDH ( developmental dysplasia of hip) and to investigate the relevance between Ⅱ type collagen and MMP-7 and the retrogression mechanism of acetabular cartilage. Methods The animal model of DDH was successfully established in 8 rabbits by applying the method of knee extension in which left lower extremity as experimental group and right one as control group.And the stains of HE and toluidine blue were applied on the samples of acetabular cartilage to observe the changes of chondrocytes and extracellular matrix ( ECM ). The techniques of immunohistocbemical staining and Western blot were employed to respectively qualify and quantitate the expression of Ⅱ type collagen and MMP-7. Results Pathohistological observation indicated the signs of retrogressive changes of acetabular cartilage in experimental group, including a loss of ECM in toluidine blue stain and a cluster of chondrocytes in HE stain. The positive numbers of Ⅱ type collagen and MMP-7 by immunohistochemical staining in experimental group were beth higher than that of control group. The quantitative amounts of Ⅱ type collagen and MMP-7 by Western blot in experimental group were both higher than that of control group. Both significant differences existed between two groups ( P < 0. 05 ). Conclusion The expression of Ⅱ type collagen and MMP-7 is correlated to a retrogression of acetabular cartilage and increases obviously in early DDH. The amount and intensity of Ⅱ type collagen and MMP-7 are probably the rationale of differential retrogression of cartilage.

Objective To investigate the expression and regulation of adiponectin in human renal glomerular endothelial cells (HRGEC). Method The adiponectin expression in human renal tissue was examined with immunohistochemistry assay, and the adiponectin mRNA and protein expression of HRGECwas confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively.PCR product was sequenced. To investigate the regulation action of TNF-α, the adiponectin produced by HRGEC was semi-quantitatively determined with real-time PCR in mRNA level and quantitatively measured with dissociation enhanced lanthanide fluorescence immunoassay (DELFIA) in protein level, respectively.Results (1) Positive adiponectin staining was observed on human glomerular capillary wall with immunohistochemistry assay. (2) Adiponectin mRNA expression in HRGEC was detected by RT-PCR, and the DNA sequence of this PCR product is consistent with adiponectin DNA sequence in Gene Bank.Adiponectin protein was also found in the supernatant of cultured HRGEC by Western blot. (3) Compared with control groups, the adipouectin mRNA expression in HRGEC determined by real-time PCR was significantly up-regulated after 250 IU/ml and 500 IU/ml TNF-α stimulation for 24 h ( P < 0. 05 and P <0. 01 ), and the adiponectin protein levels in culture supernatant measured by DELFIA were also significantly increased in these two groups ( P < 0. 05 and P < 0. 01 ). (4) Compared with control groups, the adiponectin mRNA expression in HRGEC was significantly up-regulated after 500 IU/ml TNF-α stimulation for 6 h, 12 h and 24 h (P<0.05, P<0. 05 and P<0. 01), and the adiponectin protein levels in culture supernatant were also significantly increased after stimulation for 24 h and 48 h ( P < 0. 01 ). ConclusionsHRGEC is able to synthesize adiponectin, and TNF-α can up-regulate its mRNA and protein expression.

Objective To investigate the impact of citrullination upon the antigenicity of fibrinogen peptides and explore the molecular mechanism of autoimmunity against citrullinated fibrinogen in the pathogenesis of rheumatoid arthritis (RA). Methods Human fibrinogen was citrullinated in vitro by peptidylarginine deiminase ( PAD). Stimulation of citrullinated fibrinogen on PBMC ( peripheral blood mononuclear cell) from RA patients and controls was studied by measuring cellular proliferation. Then the bindings of peptides derived from fibrinogen alpha chain and its citrullinated substitute to HLA-DR4 molecule were analyzed by the prediction software. One peptide was chosen and its arginine residues were altered by citrulline residues. Wild-type and altered peptides were synthesized and their bindings to HLA-DR4molecules examined by peptide binding assay respectively. The effects of two peptides upon T cells were determined by T cell proliferation assay. Results Compared with controls, the cellular responses to citrullinated fibrinogen or wild protein were slightly higher in RA patients. However no statistical difference was found (P > 0. 05 ). As predicted, the citrullinated substitute peptide from fibrinogen alpha chain was more prone to bind to HLA-DR4 molecule than wild-type peptide and could induce a stronger proliferation of T cells than wild-type peptide (SI, 2. 26±0. 14 vs 1.65±0. 53, P<0. 01 ) in the experiments of cell lines.Conclusions Citrullination can enhance the antigenicity of fibrinogen peptides by increasing the binding of fibrinogen peptides to HLA-DR4 molecules and inducing the specific T cell activation.

Newly diagnosed epilepsy patients are mainly treated with antiepileptic drugs (AEDs), most of them stop seizures after taking one AED, some need to use multiple AEDs to control seizures, and some patients still can't control their disease after receiving multiple drugs, which is called "refractory" or "drug-resistant" epilepsy, accounting for about 1/3 of epilepsy patients ~ [1]. How to diagnose and treat these patients early and whether they can be prevented is an important problem in the diagnosis and treatment of epilepsy at present.

A 46-year-old woman was admitted to hospital on July 19, 2009 due to blowing-like murmur in her left ear for 1 month, numbness in her left face for half a month, dizziness and vomiting for 1 week. One month ago, the patient suddenly felt blowing-like murmur in her left ear without obvious inducement, and the murmur was persistent, consistent with heart beat. Half a month ago, the patient suddenly experienced acupuncture-like severe pain in her left face, which was relieved after a few seconds, and then persistent numbness in her left face appeared, distributed in the second and third branches of the trigeminal nerve. The patient went to the local hospital, and MRI showed that there was bulbous flow at the CP angle of the left tentorial margin, disordered blood vessel shadows around it (Figure 1), and empty blood vessels were visible at the left midbrain (Figure 2); MRA of the head showed that the meningopituitary trunk was obviously thickened, the tentorial marginal branch of the cerebellum supplied blood to the tentorial area, and there was hemangioma-like dilation, and the drainage vein was vaguely drained to the transverse sinus (Figure 3).

Patients with renal transplantation treated with immunosuppressive agents or coinfected with hepatitis B and hepatitis C viruses are likely to have primary liver cancer ~ [1-3]. The reasons are that the immune function is low after the application of immunosuppressive agents, and the rate of hepatitis virus infection is increased due to renal transplantation and hemodialysis.

A 60-year-old male was admitted to hospital on July 10, 2008 due to progressive dementia accompanied by slow movement for more than 3 months. He was in coma for 1 week. At the beginning of April 2008, the patient developed progressive memory loss without obvious inducement, accompanied by slow movement, unstable gait, slow response, no headache, no nausea and vomiting, occasional fever, and his body temperature was 38.5℃. He visited Shanghai Tenth People's Hospital for many times, and no obvious abnormalities were found in head CT examination and cerebrospinal fluid examination. He was given "Shuangyiping, Huatuo Regeneration Pill" and other treatments, but the effect was not good. The patient's dementia progressively aggravated, and he entered a coma state in the past 1 week, with incontinence. The patient had no history of cardiovascular and cerebrovascular diseases. Physical examination: passive posture, confusion, slow response to orbital pressure, and no stasis and ecchymosis in the skin and mucosa of the whole body.