OBJECTIVETo study the clinicopathologic features of acquired immunodeficiency syndrome (AIDS)-related lymphadenopathy and to elucidate the salient features helpful in achieving a correct pathologic differentiated diagnosis.

METHODSEighteen cases of AIDS-related lymphadenopathy were retrieved from the files of the First Affiliated Hospital of Guangxi Medical University from 2001 to 2004. Histochemical stains, including periodic acid-Schiff, acid-fast, Giemsa, Grocott stains and immunohistochemistry (EnVision method), were used to detect the presence of pathogens in tissue sections and classify them.

RESULTSFifteen of the 18 cases (83%) were stage 4 (i.e. follicular and lymphocytic depletion). Twelve cases were co-infected with Penicillium marneffei and 4 other cases with Mycobacterium, and no pathogen was found in 1. The remaining patient was complicated with diffuse large B-cell lymphoma.

CONCLUSIONSWhen presented in early stages, AIDS-related lymphadenopathy may be overlooked, especially in routine pathology practice. Awareness of the entity in patients with persistent fever and generalized lymphadenopathy is thus crucial. Florid infection with Penicillium marneffei is also considered as an important predictor for underlying AIDS. Thorough understanding of morphologic features of AIDS-related lymphadenopathy, including possible co-infection, is essential in arriving at the correct diagnosis.

AIDS-Related Complex ; microbiology ; pathology ; AIDS-Related Opportunistic Infections ; microbiology ; pathology ; Adult ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphoma, AIDS-Related ; pathology ; Lymphoma, Large B-Cell, Diffuse ; pathology ; Male ; Middle Aged ; Mycobacterium ; isolation & purification ; Mycobacterium Infections ; microbiology ; pathology ; Mycoses ; microbiology ; pathology ; Penicillium ; isolation & purification ; Retrospective Studies

OBJECTIVETo investigate the effects of phosphorylated mitogen-activated protein kinases (MAPK), including the phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), the phosphorylated protein p38 (p-p38), the phosphorylated c-Jun N-terminal kinase (p-JNK), on phosgene inhalation-induced lung injury and its relationship with matrix metalloproteinase 9 (MMP-9).

METHODSAccording to the random number table, 30 male Wistar rats were divided into air control group (C), phosgene inhalation group (P), PD98059 (specific inhibitor of ERK1/2) group, SB203580 (specific inhibitor of p38) group, and SP600125 (specific inhibitor of JNK) group, with 6 rats in each group. The number of neutrophils in the bronchoalveolar lavage fluid (BALF) was counted and the lung wet-dry ratio (W/D) was examined. The serum levels of inflammatory factors TNF-α, IL-1β, IL-6, and IL-8 were determined with ELISA. The protein expressions of p-ERK1/2, p-p38, p-JNK, and MMP-9 in lung tissue were detected with Western blotting. The mRNA level of MMP-9 in lung tissue was detected with real-time fluorescence quantitative PCR. Data were processed with one-way analysis of variance (among groups) and SNK method (paired comparison).

RESULTSCompared with those of group C [respectively (2.0 ± 0.7)×10(4) /mL and 3.7 ± 0.6], the number of neutrophils and W/D of group P [respectively (10.7 ± 1.4)×10(4) /mL and 7.6 ± 0.4] were increased. The number of neutrophils in group SB203580 and group SP600125 was respectively (8.3 ± 1.1)×10(4), (7.9 ± 1.3)×10(4)/mL, with W/D respectively 6.1 ± 1.4, 6.1 ± 0.9, all of which decreased as compared with those of group P (with P values all below 0.01). Compared with those of group C, the levels of TNF-a, IL-1β, IL-6, and IL-8 of group P were increased, but decreased in group SB203580 and group SP600125 compared with that of group P, though still higher than those of group C, and the differences were statistically significant (P < 0.05 or P<0.01). Protein quantities of p-p38 and p-JNK were higher in group P (respectively 1.19 ± 0.22 and 1.43 ± 0.14) than in group C (respectively 0.76 ± 0.06 and 0.74 ± 0.05). Compared with those of group P, the protein levels of p-ERK1/2 (0.47 ± 0.05) in group PD98059, p-p38 (0.88 ± 0.07) in group SB203580, and p-JNK (0.91 ± 0.07) in group SP600125 were significantly reduced (P < 0.05 or P < 0.01). The protein and mRNA levels of MMP-9 were higher in group P (respectively 2.23 ± 0.18 and 4.93 ± 0.12) than in group C (respectively 1.26 ± 0.14 and 1.80 ± 0.03). The protein and mRNA levels of MMP-9 in group SB203580 (respectively 1.58 ± 0.14 and 2.96 ± 0.09) and group SP600125 (respectively 1.55 ± 0.30 and 3.00 ± 0.13) were lower than those in group P (P < 0.05 or P < 0.01).

CONCLUSIONSThe phosgene inhalation can activate the MAPK signaling protein pathway by increasing expressions of p-p38 and p-JNK, which lead to an up-regulation of MMP-9, and this may contribute to the phosgene inhalation-induced lung injury.

Animals ; Burns, Inhalation ; enzymology ; Cytokines ; metabolism ; Disease Models, Animal ; Flavonoids ; pharmacology ; Imidazoles ; pharmacology ; MAP Kinase Signaling System ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Mitogen-Activated Protein Kinases ; metabolism ; Phosgene ; Phosphorylation ; Pyridines ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVEThis study aimed to investigate the expression and role of the mitogen activated protein kinases (ERK1/2, P38, JNK) in phosgene induced lung injury in rats in vivo.

METHOD30 male wistar rats were randomized into the group as follows, Gas inhalation control group, Phosgene inhalation group, and the following groups of the inhibitors of MAPK, involving SP600125, PD98059 and SB203580, 6 animals in each group, we copy the model of phosgene-induced lung injury, used the directional flow-inhalation device, the air control group inhaled the air, and the intervention groups were given PD98059 (intraperitoneal injection), SB203580 (hypodermic injection), SP600125 (intravenous) respectively before the inhalation of phosgene. The locations and quantities of three subfamilies of MAPKs (ERK1/2, P38, JNK) and p-MAPKs (p-ERK1/2, p-P38, p-JNK) were analyzed by immunohistochemistry and Western Blot analysis respectively; The histopathological changes of lung tissues, the number of neutrophil cells and the W/D were examined.

RESULTThere were rare p-ERK1/2, p-P38 and p-JNK positive expression in alveolar and airway epithelial cells in control group. while the positive cells increased strikingly in phosgene inhalation groups, these cells involved in this process mainly included alveolar epithelial cells, air way epithelial cells, pleural mesothelial cells, infiltrative inflammatory cells, interstitium fibrocytes. After the intervention of the specific inhibitor, the positive cells decreased. As Western Blot analysis show, Protein quantities of p-P38 and p-JNK were higher in phosgene inhalation groups than those in control group, and the differences were significant (P < 0.05). Protein quantities of p-ERK1/2, p-P38 and p-JNK were lower in intervention groups than phosgene inhalation group, and the differences were significant (P < 0.05, P < 0.01). The lung injury in phosgene inhalation groups was more severer compared with the control group, the typical pathological characters of acute lung injury were discovered, the increase of the number of neutrophil cells and W/D. After the intervention of the specific inhibitor SP600125 and SB203580, the number of neutrophil cells and W/D reduced, and the differences were significant (P < 0.05, P < 0.01).

CONCLUSIONPhosgene inhalation may activate the MAPK signaling pathway, and the expression of the phosphorylation of MAPKs increased, especially the P38 ang JNK. The results may contribute to the lung injury induced by phosgene.

Animals ; Inhalation Exposure ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Lung ; metabolism ; pathology ; Lung Injury ; etiology ; metabolism ; MAP Kinase Signaling System ; Male ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Mitogen-Activated Protein Kinases ; metabolism ; Phosgene ; adverse effects ; Rats ; Rats, Wistar ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To explore the effect of miRNA-195 (miR-195) on Smad7 expression and rat hepatic stellate cells line (HSC-T6) activation incuced by transforming growth factor-β1 (TGF-β1).Methods HSC-T6 were cultured in vitro,with 5 ng · mL-1 TGF-β1 as an injury factor simulating the rats liver fibrosis models.The cells divided into six groups:control group,model group (TGF-β1 group),miR-195 mimic experimental group,miR-195.mimic NC experimental group,miR-195 inhibitor experimental group and miR-195 inhibitor NC experimental group.After the HSC-T6 treated with 5 ng · mL-1 TGF-β1for 24,48,72 h,the mRNA expression of miR-195,Smad7,and α-SMA was detected by Real-time PCR.The protein expression of Smad7 was detected by Western blot.Results Under the induced by TGF-β1,the expression of miR-195 increased gradually (P ＜ 0.01),the expression of Smad7 showed a decreasing trend (P ＜ 0.05),and the expression of oα-SMA was gradually upregulated (P ＜ 0.01) with time.Compared with the model group,miR-195 mimic could promote activation of HSC-T6 induced by TGF-β1,and increase miR-195,α-SMA mRNA expression (all P ＜0.01),as well as reduce Smad7 mRNA and protein expression (all P ＜0.01);while miR-195 inhibitor could inhibit activation of HSC-T6 induced by TGF-β1,decrease miR-195,α-SMA mRNA expression (all P ＜ 0.01),as well as upregulate Smad7 mRNA and protein expression (all P ＜ 0.01).Conclusion miR-195 is involved in pro-activation of HSC-T6 by inhibiting Smad7 expression.

Objective: This study was designed to improve complete remission(CR) rate in the patients with advanced lymphoblastic lymphoma by using early extensive induction chemotherapy. Method:A total of 11 cases of untreated lymphoblastic lymphoma in Stage Ⅲ /Ⅳ were received CVDLP regimen, including cytoxan(CTX) 1000 mg/m2 d1， vincristine(VCR) 1.5 mg/m2 d1,d8,d15,d21， Adriamycin(ADR) 40 mg/m2 d1， d2， d21， L-asparaginase(L-ASP) 10000 U/m2 d15～24， Prednison 60 mg/m2 d1～28， gradually decreased dosage at d15. methotrexate＋ Ara-C IT qw× 4. Efficacy were evaluated at d28～35. Simultaneously,retrospective analysis for 9 cases of untreated lymphoblastic lymphoma in Stage Ⅲ /Ⅳ treated with 2 cycles of CHOP were made. Efficacy were evaluated at d35. Results: CVDLP group: 10/11 cases of patients achieved CR, and 1/11 case had PR, rate of complete remission was 90.9％ ;10/11 cases had Grade Ⅳ hematological toxicity,1/11 cases had Grade Ⅲ hematological toxicity(WHO). CHOP group:3/9 got CR;5/9 got PR;1/9 had MR,rate of complete remission was 33％ . 3/9 had Grade Ⅲ hematology toxicity;6/9 had GradeⅡ hematological toxicity. Conclusion:CVDLP regimen can induce higher CR rate than CHOP regimen in untreated lymphoblastic lymphoma with Stage Ⅲ /Ⅳ , but hematology toxicity was also higher than CHOP regimen. However this induction regimen is safe and viable with strengthening supportive care.

Eukaryotic initiation factor 5A (eIF-5A) contains an unusual amino acid, hypusine, which is formed post-translationally. Although eIF-5A and its hypusine modification are essential for eukaryotic cell viability, the precise physiological function of it has remained elusive. The aim of the study is to investigate how hypusine formation modulate the proliferation, cell cycle and apoptosis in leukaemia cells. The effects of 1,7-diaminoheptane (DAH), a potent inhibitor of deoxyhypusine synthase, on proliferation and cell viability of leukemia cell lines (Mo7e, TF-1 and THP-1) and MCF-7 cells, were investigated. eIF-5A expression level was detected after cell synchronization. The results showed that inhibition of cell proliferation by DAH was in a concentration-dependent manner while apoptosis was also induced at the same time. Upon treatment of the cell lines with DAH, cell growth was inhibited. Cell cycle analysis showed that DAH induced cell growth arrest at the G(1)-S boundary of the cell cycle. In synchronized MCF-7 cells, the expression level of eIF-5A peaked at G(1) phase but very low at S and G(2)/M phases. It is concluded that hypusine formation of eIF-5A exits in the regulation of cell cycle and the results suggest that eIF-5A is involved in the expression of proteins regulating transition of G(1)-S phase of cell cycle.
Cell Line, Tumor ; Diamines ; pharmacology ; G1 Phase ; physiology ; Humans ; Lysine ; analogs & derivatives ; metabolism ; Peptide Initiation Factors ; physiology ; RNA-Binding Proteins ; S Phase ; physiology

Production of Hepatitis E Virus capsid protein by high cell density culture in recombinant E. coli has been studied in 10L and 30L fermentors. The effects of different factors on growth and producing recombinant protein of E. coli have been studied by batch culture, such as different media, the ratio of phosphate and Magnesium sulfate. Comparison of fermentation performance for recombinant E. coli in different fed-methods culture has been investigated by fed-batch culture. The effects of inducing at different stages of growth and time of inducing on growth and producing recombinant protein, also obtained by fed-batch culture. At last, the solubility of inclusion body in different urea concentrations also has been obtained by fed-batch culture. The results show that the concentration of phosphate and Magnesium sulfate in the optimal media is 80mmol/L and 20mmol/L in batch culture respectively, that induction with 1.0mmol/L IPTG at mid log phase (about 45 OD at 600nm) is suitable for growth and recombinant protein expression, the cells were approaching stationary growth phase and the maximum cell OD at 600nm of 80 was achieved in 5h of fed-batch culture, and the expression level is 29.74%. The results also indicate that the solubility of inclusion body in 4mol/L urea solution induced at 37 degrees C reaches 14mg/mL, over 80% inclusion body was resolved. The culture process achieved in 10L fermentor could be successfully scaled up to 30L fenmentor with good reproducibility.
Bioreactors ; microbiology ; Colony Count, Microbial ; Escherichia coli ; genetics ; metabolism ; Hepatitis E virus ; genetics ; Nucleocapsid Proteins ; biosynthesis ; genetics ; Protein Engineering ; methods ; Recombinant Fusion Proteins ; biosynthesis ; genetics

Objective To explore the influence of drug dosage, solvent and other main influencing factors on the successful establishment of alloxan-induced hyperglycemia mouse model and the effect on the stability of this model. Methods 160 6-8-week-old Kunming mice ofSPF grade, (male:female=1:1) were used in this study.The influences of different dosages of alloxan and solvent combinations on the successful establishment rate of the model, survival rate, body weight, fasting blood glucose, blood glucose area under curve, serum insulin level and their stabilities were dynamically observed for six weeks.Results By single intraperitoneal injection of 160 mg/kg bw alloxan ( pH 4.5 citrate sodium as solvent) , we were able to obtain a stable experimental hyperglycemic mouse model with higher levels of successful establishment rate (70%), survival rate (75%), fasting blood glucose (15-20 mmol/L), glucose area under the curve (55-65 mmol/L) and a lower but not loss of serum insulin levels (21 mIU/L).Conclusions In the present study we have carefully considered the influence of main factors such as drug dosages, solvent, etc., on the alloxan-induced experimental hyperglycemic mouse model, and successfully established this model after 6-week period observation of its stability.This model may provide a useful tool in the research of experimental diabetes and hypoglycemic functional studies.

Objective In order to provide support for the rational use of drugs,we summarize the clinical characteristics of patients with drug-induced liver injury (DILI) and statistics of the allergic drugs.Methods According to the common drug-induced liver injury diagnostic criteria of our country,the clinical data of 144 hospitalized cases in the third Xiangya hospital with DILI were analyzed retrospectively,then,potential pathogenic drugs were summarized.Results A total of 144 patients with DILI were enrolled in this study:male account for 53.47％ (77/144 cases),female account for 46.53％ (67/144 cases).The average age was (44.32 ± 16.02) years old,and 50.70％ (73/144 cases) of the patients were over 40 years old.Liver injury was caused by several kinds of drugs,23.61％ (34/144 cases) were traditional Chinese medicine,20.83％ (30/144 cases)were immunosuppressive agents,15.97％ (23/144 cases) were anti-tuberculosis drugs,7.64％ (11/144 cases) were antineoplastic drugs.18.75％ (27/144 cases) patients were cured,22.92％ (33/144 cases) patients got better while others account for 58.33％ (84/144 cases),and the average hospitalization days of patients with DILI were 16 days.Age,gender and duration of the disease had no significant effect on prognosis (P ＞ 0.05),while there were significant differences between liver function indexes and prognosis (P ＜0.05).Conclusion In this study,the incidence of DILI was higher in elderly people.A variety of drugs were able to cause DILI,including traditional Chinese medicine,immunosuppressive agents and anti-tuberculosis drugs.

BACKGROUNDWith the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.

METHODSAll infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.

RESULTSA total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.

CONCLUSIONSOur study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

China ; Female ; Humans ; Infant ; Infant Mortality ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; statistics & numerical data ; Male ; Morbidity ; Respiratory Distress Syndrome, Newborn ; mortality ; Retrospective Studies ; Surveys and Questionnaires