Protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae against myocardial injury in septic mice / 南方医科大学学报

OBJECTIVE@#To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice.@*METHODS@#Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR.@*RESULTS@#Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05).@*CONCLUSION@#Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.

Protective effect of recombinant adult serine protease inhibitor from Trichinella spiralis on sepsis-associated acute kidney injury in mice / 中国血吸虫病防治杂志

Objective To investigate the protective effect of recombinant adult serine protease inhibitor from Trichinella spiralis (TsadSPI) on sepsis-associated acute kidney injury in mice. Methods A total of 18 male BALB/c mice were randomly divided into the sham-operation group, the model group, and the TsadSPI treatment group, of 6 mice in each group. Sepsis-associated acute kidney injury was modeled in the model group and TsadSPI treatment group by cecal ligation puncture (CLP), while mice in the sham-operation group were only given exploratory laparotomy without ligation or perforation of the cecum. After 30 min of CLP, mice in the sham-operation group and the model group were intraperitoneally injected with PBS (100 μL), and mice in the TsadSPI treatment group were intraperitoneally injected with PBS (100 μL) containing TsadSPI (2 μg). At 12 h following modeling, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and urea nitrogen (BUN) were measured to assess the liver and kidney functions, and the changes of the mouse kidney structure were observed using HE staining. In addition, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β were measured using an enzyme-linked immunosorbent assay (ELISA), and the myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB) p65 expression was determined in kidney tissues using immunohistochemical staining. Results At 12 h following CLP, there were significant differences in the serum levels of ALT (F = 41.031, P < 0.001), AST (F = 54.757, P < 0.001), Cr (F = 24.142, P < 0.001) and BUN (F = 214.849, P < 0.001) among the three groups, and higher levels of ALT, AST, Cr and BUN were measured in model group than in the sham-operation group (P < 0.001), while lower ALT, AST, Cr and BUN levels were found in the TsadSPI treatment group than in the model group (P < 0.001). HE staining showed severe mouse kidney injuries following CLP, and TsadSPI treatment resulted in remarkable alleviation of the injury. ELISA measured significant differences in the TNF-α (F = 47.502, P < 0.001) and IL-6 levels (F = 222.061, P < 0.001) among the three groups, and showed a remarkable reduction in the TNF-α and IL-6 levels in the TsadSPI treatment group as compared to those in the model group (P < 0.001). In addition, there were significant differences in serum IL-10 (F = 16.227, P < 0.001) and TGF-β levels (F = 52.092, P < 0.001) among the three groups, and higher IL-10 and TGF-β levels were seen in the TsadSPI treatment group than in the model group (P < 0.001). Immunohistochemical staining showed greater MyD88 expression and a higher nuclear positive rate of NF-κB p65 in kidney tissues in the model group than in the TsadSPI treatment group. Conclusions TsadSPI may reduce the MyD88 expression and nuclear positive rate of NF-κB p65 in mouse kidney tissues to up-regulate the expression of immunomodulatory factors and down-regulate the expression of pro-inflammatory cytokines, thereby protecting sepsis-associated acute kidney injury.

Research Advances on Treatment of Multiple Myeloma Bone Disease--Review / 中国实验血液学杂志

The main features of multiple myeloma bone disease (MBD) are hyperactivity of systemic bone destruction and inhibition of new bone formation. Its clinical manifestations include pain, osteoporosis, pathologic fractures and associated nerve compression symptoms etc. MBD is one of the most common complications of multiple myeloma (MM). Its misdiagnosis rate is higher, and the patients' quality of life and prognosis are poor. This review discusses the most recent advancement on its pathogenesis and novel therapies, so as to provide reference for clinical treatment of MBD.

Complete nucleotide sequence of a human coxsackievirus B3 strain A103/KM/09 isolated in Yunnan province, 2009 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To analyze the genetic characterization of the complete genome from a human coxsackievirus B3 strain A103/KM/09 isolated in Yunnan province, 2009.</p><p><b>METHODS</b>By using RT-PCR, all the eight fragments which containing about 1000 nucleotides and covering full viral genome, were sequenced. By using Mega 5.05,Geneious, RDP 3 and SimPlot 3.5.1 software, sequences were aligned with other enterovirus reference sequences. Phylogenetic and recombination analysis were also carried out.</p><p><b>RESULTS</b>The A103/KM/09 isolate genome showed 7389 nucleotides in length , encoding for 2185 amino acids. In the complete genome, the homology of nucleotide and amino acid among the seven coxsackievirus B3 isolates were 81.0%-88.0% and 95.7%-98.0%, respectively. There appeared 81.0% and 95.7% homology when compared with that of Nancy prototype strain. Results from the Phylogenetic analysis showed that the coxsackievirus B3 formed five distinct clades, I-V. Nucleotide divergence rates between clades were 16.2%-24.3% . The A103/KM/09 strain belonged to clade V. Clade V was further divided into four sub-clades,A-D. The nucleotide divergence between sub-clades was 4.3%-11.4%. Putative recombinant event for A103/ KM/09 was detected.</p><p><b>CONCLUSION</b>All coxsackievirus B3 isolates could be divided into five clades, with A103/KM/09 strain belonged to Clade V-D. Evolution of coxsackievirus B3 had occurred in China.</p>

Aberrant DNA methylation in cervical carcinogenesis / 癌症

Persistent infection with high-risk types of human papillomavirus(HPV) is known to cause cervical cancer; however, additional genetic and epigenetic alterations are required for progression from precancerous disease to invasive cancer. DNA methylation is an early and frequent molecular alteration in cervical carcinogenesis. In this review, we summarize DNA methylation within the HPV genome and human genome and identify its clinical implications. Methylation of the HPV long control region (LCR) and L1 gene is common during cervical carcinogenesis and increases with the severity of the cervical neoplasm. The L1 gene of HPV16 and HPV18 is consistently hypermethylated in invasive cervical cancers and can potentially be used as a clinical marker of cancer progression. Moreover, promoters of tumor suppressor genes (TSGs) involved in many cellular pathways are methylated in cervical precursors and invasive cancers. Some are associated with squamous cell carcinomas, and others are associated with adenocarcinomas. Identification of methylated TSGs in Pap smear could be an adjuvant test in cervical cancer screening for triage of women with high-risk HPV, atypical squamous cells of undetermined significance, or low grade squamous intraepithelial lesion (LSIL). However, consistent panels must be validated for this approach to be translated to the clinic. Furthermore, reversion of methylated TSGs using demethylating drugs may be an alternative anticancer treatment, but demethylating drugs without toxic carcinogenic and mutagenic properties must be identified and validated.

Epidemiological analysis of maternal death in Beijing from 1995 to 2010 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To analysis the trend of maternal death time and explore the impact of the variety of death causes and birth place to maternal death time.</p><p><b>METHODS</b>According to the data provided by Beijing Maternal and Children Health Hospital, the 372 death cases of pregnant and lying-in women from 1995 to 2010, a retrospective study was performed to analyze the death causes, maternal death time and the influencing factors.</p><p><b>RESULTS</b>The MMR declined from 27.9 per 100 000 live births from 1995 to 2000 to 14.8 per 100 000 live births from 2006 to 2010, with a decline of 46.9%. Among the maternal death within 24 hours of delivery, 79.7% (106/133) died of obstetric hemorrhage, hypertensive disorder complicating pregnancy and amniotic fluid embolism. It took up 47.8% (64/134) from 1995 to 2000, reduced to 37.5% (45/120) from 2006 to 2010. At the same time, the maternal mortality ratio within 24 hours reduced from 40.2%(54/134) to 28.3% (34/120), the variation of death time was consistent with the causes of maternal mortality (χ² = 59.109, P < 0.05). Indirect obstetric causes increased significantly from 2006 to 2010, 53.2% (33/62) of pregnant women with heart disease, cerebrovascular disease and pulmonary embolism died in prenatal or more than 120 hours postnatal. Among the maternal death delved in hospital, 29.0% (29/100) died within 24 hours, 52 cases delved at home or in private clinics, 43 cases (82.6%) died within 24 h postnatal. There were significant differences between birth place and death time (χ² = 24.500, P < 0.05).</p><p><b>CONCLUSION</b>Maternal death time changed from 24 hours of delivery to prenatal or postnatal a long time. The maternal mortality causes and hospital delivery is an important factor affecting maternal time.</p>

Study on maternal deaths in Beijing, from 1996 to 2010 / 中华流行病学杂志

Objective To provide evidence for further reducing the maternal mortality rate (MMR) through analyzing the causes of death and influencing factors on the issue.Methods Every maternal death from 1996 to 2010 was audited by experts and relevant information was collected and analyzed,retrospectively.Results (1) The overall MMR among Beijing residents was 20.2 per 100 000 live births in 1996-2000 while decreased to 14.2 per 100 000 live births from 2006 to 2010.At the same time,the MMR of migrating people decreased from 47.7 to 15.2 per 100 000 live births.(2) The proportion of women having received middle school education and above,increased from 59.8％ to 78.8％ and the non-prenatal care maternal ratio decreased from 39.1％ to 12.7％.(3) Among the 349 deaths in the period of 1996-2010,209 (59.9％) were caused by direct obstetric reasons.Proportion of obstetric hemorrhage declined from 14.4％ to 9.2％ and the amniotic fluid embolism declined from 20.7％ to 15.0％.Prolific,non-prenatal care and private clinics/home deliveries were important factors on direct obstetric reasons.71.4％ maternal mortality of indirect causes appeared abnormal during pregnancy.(4) The WHO twelve-grade classification standard on maternal deaths was adopted.Our data showed that the main reasons causing maternal deaths of Beijing residents were related to the skills of medical staffs (62.4％) and healthcare management (19.7％).The main reasons of maternal deaths among migrating people would include:poor knowledge (41.4％),inappropriate attitude(32.3％) and resources of the families(24.0％).Conclusion The MMR in Beijing continuously declined from 1996 to 2010.However,in order to keep up with the changing causes related to maternal deaths as well as to the increasing service requirements,it is necessary to develop a new model on service and management of the issue.

Genetic characteristics on the small hydrophobic protein and hemagglutinin-neuraminidase genes of mumps virus in Yunnan province,China from 2007 to 2009 / 中华流行病学杂志

Objective To analyze genetic characterization of the small hydrophobic and hemagglutinin-neuraminidase genes of mumps virus(MuV)isolated in Yunnan province,China from 2007 to 2009.Methods Fourteen MuV strains were isolated in Yunnan,China from 2007 to 2009.Using RT-PCR,the SH gene fragments contained 316 nucleotides in all strains and HN gene of six strains were sequenced.The sequences were aligned with other mumps virus sequences downloaded from GenBank using Mega 4.1 software.Results Fourteen isolated strains were closely related to other reference strains of F genotypes.In SH gene,the homology of nucleotide and amino acid among the fourteen isolated strains were 98.3%-100.0%and 96.5%-100.0%,respectively,and 92.6%%-99.4%and 87.7%-100.0% of homology when compared with that of strains isolated from other provinces in China,respectively.Wsh1 and Wsh2 strains had less homology when compared to other strains of F genotypes.The fourteen strains had homology of 84.5%-85.1%and 77.2%compared to vaccine strains on nucleotide and amino acid,respectively,and had homology of 83.4%-90.9% and 70.1%-86.0% compared to that of other genotypes.In HN gene,the homology of nucleotide and amino acid among the six isolated strains were 99.3%-99.5% and 99.1%-99.7%,respectively,and also 99.8% and 99.8% of homology respectively when compared to the SP strain in China.All the six strains had homology of 92.4%-93.2% and 95.5%-96.4% when compared to the vaecine strains on nucleotide and amino acid,respectively,and had homology of 94.7%-96.8% and 95.5%-99.1%compared to other genotypes.Conclusion Fourteen strains isolated in Yunnan from 2007 to 2009belonged to F genotype of MuV while the HN gene seemed more conservative than SH gene.

Study on the maternal mortality ratio from 1995 to 2004 among residential and migrant women in Beijing / 中华流行病学杂志

<p><b>OBJECTIVE</b>To analyze the maternal mortality ratio (MMR) of residential and migrant women in Beijing.</p><p><b>METHODS</b>A retrospective study from 1995 to 2004 was performed to analyze data from the maternal death cases.</p><p><b>RESULTS</b>The MMR of resident and migrant of Beijing from 1995 to 2004 were 17.9 and 51.3 per ten thousand respectively. The main reasons of maternal deaths among residents were embolism (21.2%), hypertensive disorder complicating pregnancy (18.3%), postpartum hemorrhage (14.4%) and ectopic pregnancy/heart disease (9.6%). The main reasons of migrant maternal deaths were postpartum hemorrhage (25.2%), embolism (19.7%), hypertensive disorder complicating pregnancy (17.3%) and liver disease (9.5%). The avoidable deaths were accounted for 18.9%.</p><p><b>CONCLUSION</b>The MMR in Beijing local residents was close to that in developed countries. To further reduce MMR in Beijing would depend on the better administration of related issues among floating population. Poor quatily delivery must be banned together with strengthening the training programs on health workers. It is also important to improve the knowledge and skills of medical staff for rescuing the complications of pregnancy and ectopic pregnancy.</p>