Background

Expanding HIV testing is important among individuals at increased risk for sexual HIV transmission in China, but little is known about prior HIV testing experiences among sexually transmitted disease (STD) patients.

Methods

This cross-sectional study of 1792 outpatients from six public sexually transmitted disease (STD) clinics in Guangdong Province recorded detailed information about ever having been tested for HIV infection in addition to socio-demographic variables, health seeking, clinical STD history, and HIV stigma using a validated survey instrument.

Results

456 (25.4%) of the STD patients in this sample had ever been tested for HIV infection. STD patients who were male, had higher income, more education, were at City A and City C, received STD services at public facilities, had used intravenous drugs, and had a history of an STD were more likely to ever receive an HIV test in multivariate analysis. Low perceived HIV risk was the most common reason for not receiving an HIV test. Only 7.7% of the sample reported fear of discrimination or loss of face as influencing their lack of HIV testing.

Conclusion

Incomplete prior HIV screening among STD patients in China suggests the need for broadening HIV testing opportunities at STD clinics and similar clinical settings attended by those with increased sexual risk.

Background

Female sex workers (FSWs) have become one of the key populations for HIV/STI control in China. Categorization of FSWs can help prioritize HIV/STI intervention efforts. We examined two possible categorizations of FSWs and the relationship with syphilis infection risk in Liuzhou City, China.

Methods

From October 2009 to February 2010, a total of 583 FSWs recruited by respondent-driven sampling in a cross-sectional survey were tested for syphilis and interviewed to collect socio-demographic and behavioural information. Respondents were categorized based on transaction price for vaginal sex and type of sex work location. The relationship between the two categorizations and syphilis infection risk was assessed using univariate and multivariate logistic regression analysis.

Results

The prevalence rates of lifetime and active syphilis infection were 8.6% and 4.1% respectively. Lifetime and active syphilis prevalence were higher among FSWs in the lowest price category (52.7% and 25.4% respectively) and those working in streets (69.7% and 39.8% respectively) or through telephone (46.3% and 17.0% respectively). Multivariate analysis showed that lifetime syphilis prevalence was significantly higher among street-(Adjusted odds ratio AOR 38.7, 95% CI 10.7-139.9) and telephone-based FSWs (AOR 10.8, 95% CI 3.3-35.1), and that active syphilis prevalence was significantly higher among street-based FSWs (AOR 15.2, 95% CI 3.7-62.1) after adjusting for demographic and behavioural factors.

Conclusions

Categorization based on sex work location was more closely related to the risk of syphilis infection than the price classification. Street- and telephone-based FSWs had significantly higher risk of syphilis infection. Focused interventions among these particular high-risk FSWs subgroups are warranted.

Background

Sexually transmitted infections (STIs) have become a major public health problem among female sex workers (FSWs) in China. There have been many studies on prevalences of HIV and syphilis but the data about Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections are limited in this population in China.

Methods

A cross-sectional study was performed among FSWs recruited from different types of venues in 8 cities in China. An interview with questionnaire was conducted, followed by collection of a blood and cervical swab specimens for tests of HIV, syphilis, NG and CT infections.

Results

A total of 3,099 FSWs were included in the study. The overall prevalence rates of HIV, syphilis, NG and CT were 0.26%, 6.45%, 5.91% and 17.30%, respectively. Being a FSW from low-tier venue (adjusted odds ratios [AOR]=1.39) had higher risk and being age of ≥ 21 years (AOR=0.60 for 21–25 years; AOR=0.29 for 26–30 years; AOR=0.35 for 31 years or above) had lower risk for CT infection; and having CT infection was significantly associated with NG infection.

Conclusions

The high STI prevalence rates found among FSWs, especially among FSWs in low-tier sex work venues, suggest that the comprehensive prevention and control programs including not only behavioral interventions but also screening and medical care are needed to meet the needs of this population.

The interleukin-23 (IL-23) and its receptor (IL-23R) mediate the direct antitumor activities in human hematologic malignancies including pediatric acute leukemia. Two potentially functional genetic variants (IL-23R rs1884444 T>G and rs6682925 T>C) have been found to contribute to solid cancer susceptibility. In this study, we conducted a case-control study including 545 acute myeloid leukemia (AML) patients and 1,146 cancer-free controls in a Chinese population to assess the association between these two SNPs and the risk of AML. We found that IL-23R rs1884444 TG/GG and rs6682925 TC/CC variant genotypes were associated with significantly increased risk of AML [rs1884444: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.01–1.62; rs6682925: adjusted OR = 1.30, 95%CI = 1.01–1.67], compared to their corresponding wild-type homozygotes, respectively. These findings indicated that genetic variants in IL-23R may contribute to AML risk in our Chinese population.

Background

Serum phosphorus control is critical for chronic kidney disease (CKD) 5D patients. Currently, clinical profile for an oral phosphorus binder in the mainland Chinese population is not available.

Objective

To establish the efficacy, safety, and tolerability of lanthanum carbonate in CKD 5D patients.

Design

Multicenter, randomized, double blind, placebo-controlled study. A central randomization center used computer generated tables to allocate treatments.

Setting

Twelve tertiary teaching hospitals and medical university affiliated hospitals in mainland China.

Participants

Overall, 258 hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) adult patients were enrolled.

Intervention

After a 0–3-week washout period and a 4-week lanthanum carbonate dose-titration period, 230 patients were randomized 1:1 to receive lanthanum carbonate (1500 mg-3000 mg) or placebo for a further 4-week maintenance phase.

Main outcome measures

Efficacy and safety of lanthanum carbonate to achieve and maintain target serum phosphorus concentrations were assessed.

Results

In the titration phase, serum phosphorus concentrations of all patients decreased significantly. About three-fifths achieved target levels without significantly disturbing serum calcium levels. At the end of the maintenance period, the mean difference in serum phosphorus was significantly different between the lanthanum carbonate and placebo-treated groups (0.63±0.62 mmol/L vs. 0.15±0.52 mmol/L, P < 0.001). The drug-related adverse effects were mild and mostly gastrointestinal in nature.

Conclusion

Lanthanum carbonate is an efficacious and well-tolerated oral phosphate binder with a mild AE profile in hemodialysis and CAPD patients. This agent may provide an alternative for the treatment of hyperphosphatemia in CKD 5D patients in mainland China.

Trial registration

No. ChiCTR-TRC-10000817

Summary

Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. To identify mutations that drive medulloblastoma we sequenced the entire genomes of 37 tumours and matched normal blood. One hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma: several target distinct components of the epigenetic machinery in different disease subgroups, e.g., regulators of H3K27 and H3K4 trimethylation in subgroup-3 and 4 (e.g., KDM6A and ZMYM3), and CTNNB1-associated chromatin remodellers in WNT-subgroup tumours (e.g., SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours, identified genes that maintain this cell lineage (DDX3X) as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumourigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development.

The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states. Our current understanding of Wnt signaling in osteogenesis elucidates the molecular mechanisms of classic osteogenic pathologies. Activating and inactivating aberrations of the canonical Wnt signaling pathway in osteogenesis results in sclerosteosis and osteoporosis respectively. Recent studies have sought to target the Wnt signaling pathway to treat osteogenic disorders. Potential therapeutic approaches attempt to stimulate the Wnt signaling pathway by upregulating the intracellular mediators of the Wnt signaling cascade and inhibiting the endogenous antagonists of the pathway. Antibodies against endogenous antagonists, such as sclerostin and dickkopf-1, have demonstrated promising results in promoting bone formation and fracture healing. Lithium, an inhibitor of glycogen synthase kinase 3β, has also been reported to stimulate osteogenesis by stabilizing β catenin. Although manipulating the Wnt signaling pathway has abundant therapeutic potential, it requires cautious approach due to risks of tumorigenesis. The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential.

Nicholas Tan and colleagues use a decision analytic model to quantify the impact of the ten-year national syphilis control plan in China and conclude that earlier and more extensive screening are also necessary for reaching policy goals.

Background

Syphilis is a major public health problem in many regions of China, with increases in congenital syphilis (CS) cases causing concern. The Chinese Ministry of Health recently announced a comprehensive 10-y national syphilis control plan focusing on averting CS. The decision analytic model presented here quantifies the impact of the planned strategies to determine whether they are likely to meet the goals laid out in the control plan.

Methods and Findings

Our model incorporated data on age-stratified fertility, female adult syphilis cases, and empirical syphilis transmission rates to estimate the number of CS cases associated with prenatal syphilis infection on a yearly basis. Guangdong Province was the focus of this analysis because of the availability of high-quality demographic and public health data. Each model outcome was simulated 1,000 times to incorporate uncertainty in model inputs. The model was validated using data from a CS intervention program among 477,656 women in China. Sensitivity analyses were performed to identify which variables are likely to be most influential in achieving Chinese and international policy goals. Increasing prenatal screening coverage was the single most effective strategy for reducing CS cases. An incremental increase in prenatal screening from the base case of 57% coverage to 95% coverage was associated with 106 (95% CI: 101, 111) CS cases averted per 100,000 live births (58% decrease). The policy strategies laid out in the national plan led to an outcome that fell short of the target, while a four-pronged comprehensive syphilis control strategy consisting of increased prenatal screening coverage, increased treatment completion, earlier prenatal screening, and improved syphilis test characteristics was associated with 157 (95% CI: 154, 160) CS cases averted per 100,000 live births (85% decrease).

Conclusions

The Chinese national plan provides a strong foundation for syphilis control, but more comprehensive measures that include earlier and more extensive screening are necessary for reaching policy goals.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Every year, 1.5 million pregnant women are infected with syphilis, a bacterial infection that is usually transmitted during sexual contact but that can also pass from a mother to her unborn child. In many of these women, the disease is detected through routine antenatal testing and is successfully treated with penicillin. But among those women who are not treated, about half experience adverse outcomes—the death of their baby during early or late pregnancy (fetal death and stillbirth, respectively) or soon after birth (neonatal death), or the birth of an infected baby. Babies born with syphilis (congenital syphilis) often fail to thrive and can develop problems such as blindness, deafness, and seizures if not treated. In 2008, syphilis in pregnancy contributed to 305,000 fetal deaths, stillbirths, and neonatal deaths, and 215,000 babies were affected by other adverse consequences of congenital syphilis. Yet congenital syphilis is simple and cheap to eliminate—a few injections of penicillin can clear the infection in a pregnant woman, and screening all pregnant women for syphilis is feasible even in low-resource settings.

Why Was This Study Done?

Congenital syphilis has recently reemerged in China. In the 1990s, there were very few cases of congenital syphilis in China, but by 2009, the reported incidence of congenital syphilis had risen to 139 cases per 100,000 live births. In 2010 the Chinese Ministry of Health announced a ten-year National Syphilis Prevention and Control Plan (NSCP) that, in line with World Health Organization (WHO) recommendations, aims to reduce the incidence of congenital syphilis to fewer than 30 cases per 100,000 live births by 2015 and to fewer than 15 cases per 100,000 live births by 2020. China's strategy for achieving these targets includes increasing prenatal syphilis screening coverage to 80% in urban areas and 60% in rural areas, increasing treatment rates among infected women to 90% in urban areas and 70% in rural areas, and increasing syphilis awareness among adults. But will this strategy be sufficient? Here, the researchers develop a mathematical model to quantify the likely impact of the NSCP's strategy on the incidence of congenital syphilis in southern China.

What Did the Researchers Do and Find?

The researchers developed a decision analytic model in which women move through a sequence of health states from uninfected, through infection and pregnancy, and to the development of congenital syphilis, and fed data collected in Guangdong Province between 2005 and 2008 on women's fertility, female syphilis cases, and syphilis transmission rates into the model. The researchers checked that their model provided estimates of the incidence of congenital syphilis that matched the reported incidence for Guangdong Province (internal validation) and the reported incidence in a congenital syphilis intervention program in Shenzhen, Guangdong (external validation). They then used their model to identify which parts of the NSCP strategy are likely to have the greatest effect on the incidence of congenital syphilis. Increasing prenatal screening coverage was the single most effective strategy for the reduction of congenital syphilis, but neither this strategy alone nor implementation of the whole NPSC strategy achieved the plan's target outcomes. By contrast, a four-pronged approach (95% coverage of prenatal screening, 75% of screening during the first two-thirds of pregnancy, 95% treatment completion, and having an accurate screening test) reduced the estimated incidence of congenital syphilis cases to 27 per 100,000 live births.

What Do These Findings Mean?

These findings suggest that although the NSCP is a strong foundation for control of congenital syphilis in China, more comprehensive measures will be needed to reach the plan's policy goals. In particular, the findings suggest that earlier and more extensive screening will be needed to reduce the incidence of congenital syphilis to below 30 cases per 100,000 live births, WHO's benchmark for congenital syphilis control. The accuracy of these findings is limited by the assumptions included in the model and by the data fed into it. Moreover, because the data included in the model came from Guangdong Province, these findings may not apply elsewhere in China or in other countries. Nevertheless, this study illustrates the importance of using multi-pronged approaches to address the complex problem of congenital syphilis control and identifies some strategies that are likely to improve the control of this important public health problem.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001375.

The World Health Organization provides information on sexually transmitted infections, including details of its strategy for the global elimination of congenital syphilis, the investment case for the elimination of mother-to-child transmission of syphilis, and regional updates on progress towards elimination (some information is available in several languages)

The US Centers for Disease Control and Prevention has a fact sheet on syphilis

The UK National Health Service Choices website also has a page on syphilis

MedlinePlus provides information on congenital syphilis and links to additional syphilis resources (in English and Spanish)

Haiti: Congenital Syphilis on the Way Out is a YouTube video describing the introduction of rapid diagnostic tests for syphilis in remote parts of Haiti

Objective

To present our experience of combining transperitoneal mini-laparoscopic pyeloplasty (mini-LP) and concomitant ureteroscopy-assisted pyelolithotomy (U-P) for ureteropelvic junction obstruction (UPJO) complicated by renal caliceal stones in the same session.

Methods

Between May 2007 and December 2011, mini-LP and concomitant U-P was performed in nine patients with UPJO and ipsilateral renal caliceal stones. Stone location and burden were preoperatively assessed. After pyelotomy with appropriate length (about 4 mm), a 16-Fr catheter sheath replaced the uppermost or lowermost laparoscopic trocar and was introduced directly into the renal pelvis under the guidance of a guide wire and laparoscopic vision. A 7.5F rigid ureteroscopy passed through the catheter sheath into the plevis. Intracorporeal lithotripsy and/or pressure irrigation via a pump was used for caliceal stone removal. Subsequently, laparoscopic pyeloplasty was performed in a standard fashion. Postoperative imaging was assessed.

Results

The calculi sizes ranged from 2 to 11 mm (mean, 7.1 mm) and an average of 3 stones per patient was removed (range, 1 to 6 stones). Complete stone clearance confirmed by postoperative imaging was achieved in all patients. Mean operative time was 210 minutes, and estimated blood loss was 20 mL. Mean hospital stay was 5 days (4–7). Stent was removed after 4–8 weeks. No intraoperative or postoperative complications were noted during a mean follow-up of 18.5 months (range, 6 to 24 months).

Conclusions

Mini-LP and concomitant U-P are simple and effective alternatives for the simultaneous management of UPJO complicated by coexisting ipsilateral renal caliceal stones.

SUMMARY

RIG-I and MDA5 detect viral RNA in the cytoplasm and activate signaling cascades leading to the production of type-I interferons. RIG-I is activated through sequential binding of viral RNA and unanchored lysine-63 (K63) polyubiquitin chains, but how polyubiquitin activates RIG-I and whether MDA5 is activated through a similar mechanism remain unresolved. Here we showed that the CARD domains of MDA5 bound to K63 polyubiquitin and that this binding was essential for MDA5 to activate the transcription factor IRF3. Mutations of conserved residues in MDA5 and RIG-I that disrupt their ubiquitin binding also abrogated their ability to activate IRF3. Polyubiquitin binding induced the formation of a large complex consisting of four RIG-I and four ubiquitin chains. This hetero-tetrameric complex was highly potent in activating the antiviral signaling cascades. These results suggest a unified mechanism of RIG-I and MDA5 activation and reveal a unique mechanism by which ubiquitin regulates cell signaling and immune response.

Background

Accessibility of syphilis testing services is critical in syphilis control programs for female sex workers (FSWs), but few FSWs attend public STI clinics or other testing sites. Introduction of free rapid syphilis testing (RST) into outreach programs for FSWs will help improve test uptake.

Methods

Commercial sex venues were identified in two cities in South China. In cooperation with health advocacy organizations, health outreach teams from local public health or medical facilities approached all types of sex venues in study areas to offer free RST. Acceptability and uptake of RST among FSWs were evaluated.

Results

A total of 2812 FSWs were offered RST and 2670 (95.0%) accepted syphilis testing. 182 (6.8%) FSWs had a positive RST result among whom 136 (74.7%) were willing to attend an STD clinic for confirmatory testing and treatment. More than half (89, 66.4%) of those with syphilis were not willing to notify their sex partners. Multivariate logistic analysis showed that syphilis test uptake was associated with residing in Jiangmen (AOR, 1.78; 95% CI, 1.15–2.77), older age (AOR, 2.11, 95% CI, 1.17–3.79 for age of 31 years or above), and not working at a service venue (AOR, 1.60; 95% CI, 1.10–2.34).

Conclusions

RST at sex venues is well accepted by FSWs when it is integrated into ongoing outreach services. Such programs provide excellent opportunities for expanding syphilis screening efforts among specific subgroups of FSW who are difficult to reach through clinic-based programs.

Context

Neuroblastoma is diagnosed over a wide age range from birth through young adulthood, and older age at diagnosis is associated with a decline in survivability.

Objective

To identify genetic mutations that are associated with age at diagnosis in patients with metastatic neuroblastoma.

Design, Setting and Patients

We performed whole genome sequencing of DNA from diagnostic tumors and their matched germlines from 40 patients with metastatic neuroblastoma obtained between 1987 and 2009. Age groups at diagnosis included infants (0-<18 months), children (18 months-<12 years), and adolescents and young adults (≥12 years). To confirm the findings from this discovery cohort, validation testing using tumors from an additional 64 patients obtained between 1985 and 2009 was also performed. Formalin-fixed paraffin-embedded tumor tissue was used for immunohistochemistry and fluorescent in situ hybridization. Telomere lengths were analyzed using the whole genome sequencing data, quantitative polymerase chain reaction and fluorescent in situ hybridization.

Main Outcome Measure

Somatic recurrent mutations in tumors from patients with neuroblastoma correlated with the age at diagnosis and telomere length.

Results

We identified mutations in the ATRX gene in 100% (5/5) (95% CI, 50% – 100%) of tumors from patients in the adolescent and young adult group, 17% (5/29) (95% CI, 7% – 36%) of tumors from children, and 0% (0/6) (95% CI, 0% – 40%) of tumors from infants in the discovery cohort (n=40). In the validation cohort (n=64), we identified mutations in the ATRX gene in 33% (9/27) (95% CI, 17% – 54%) of tumors from patients in the adolescent and young adult group, 16% (4/25) (95% CI, 6% – 35%) of tumors from children, and 0% (0/12) (95% CI, 0% – 24%) of tumors from infants. We identified mutations in the ATRX gene in 44% (14/32) (95% CI, 28% – 62%) of tumors from patients in the adolescent and young adult group, 17% (9/54) (95% CI, 9% – 29%) of tumors from children, and 0% (0/18) (95% CI, 0% – 17%) of tumors from infants in the combined cohort (n=104). ATRX mutations were associated with an absence of ATRX protein in the nucleus and with long telomeres.

Conclusions

ATRX mutations were associated with age at diagnosis in children and young adults with stage 4 neuroblastoma.

Clinical Protocol

“Molecular Characterization of Neuroblastic Tumor: Correlation with Clinical Outcome” (clinical trials.gov: NCT00588068).

Background

Telomeres are the protective arrays of tandem TTAGGG sequence and associated proteins at the termini of chromosomes. Telomeres shorten at each cell division due to the end-replication problem and are maintained above a critical threshold in malignant cancer cells to prevent cellular senescence or apoptosis. With the recent advances in massive parallel sequencing, assessing telomere content in the context of other cancer genomic aberrations becomes an attractive possibility. We present the first comprehensive analysis of telomeric DNA content change in tumors using whole-genome sequencing data from 235 pediatric cancers.

Results

To measure telomeric DNA content, we counted telomeric reads containing TTAGGGx4 or CCCTAAx4 and normalized to the average genomic coverage. Changes in telomeric DNA content in tumor genomes were clustered using a Bayesian Information Criterion to determine loss, no change, or gain. Using this approach, we found that the pattern of telomeric DNA alteration varies dramatically across the landscape of pediatric malignancies: telomere gain was found in 32% of solid tumors, 4% of brain tumors and 0% of hematopoietic malignancies. The results were validated by three independent experimental approaches and reveal significant association of telomere gain with the frequency of somatic sequence mutations and structural variations.

Conclusions

Telomere DNA content measurement using whole-genome sequencing data is a reliable approach that can generate useful insights into the landscape of the cancer genome. Measuring the change in telomeric DNA during malignant progression is likely to be a useful metric when considering telomeres in the context of the whole genome.

qnr, aac(6′)-Ib-cr, qepA, and oqxAB genes were detected in 5.7%, 4.9%, 2.6%, and 20.2% of 1,022 Escherichia coli isolates from humans, animals, and the environment, respectively, collected between 1993 and 2010 in China. The prevalence of oqxAB in porcine isolates (51.0%) was significantly higher than that in other isolates. This is the first report of oqxAB-positive isolates from ducks and geese and as early as 1994 from chickens.

One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which alters the expression of IL3 by affecting the binding affinity of transcription factor SP1. Further analysis indicated that IL3 and its receptors are continuously expressed in the developing mouse brain, reaching highest levels at postnatal day 1–4. Furthermore, we found IL3 receptor alpha (IL3RA) was mainly expressed in neural progenitors and neurons, and IL3 could promote proliferation and survival of the neural progenitors. The expression level of IL3 thus played pivotal roles in the expansion and maintenance of the neural progenitor pool and the number of surviving neurons. Moreover, we found that IL3 activated both estrogen receptors, but estrogen didn’t directly regulate the expression of IL3. Our results demonstrate that genetic variation in the IL3 promoter regulates human brain volume and reveals novel roles of IL3 in regulating brain development.

Protein lysine acetylation is a type of reversible post-translational modification that plays a vital role in many cellular processes, such as transcriptional regulation, apoptosis and cytokine signaling. To fully decipher the molecular mechanisms of acetylation-related biological processes, an initial but crucial step is the recognition of acetylated substrates and the corresponding acetylation sites. In this study, we developed a position-specific method named PSKAcePred for lysine acetylation prediction based on support vector machines. The residues around the acetylation sites were selected or excluded based on their entropy values. We incorporated features of amino acid composition information, evolutionary similarity and physicochemical properties to predict lysine acetylation sites. The prediction model achieved an accuracy of 79.84% and a Matthews correlation coefficient of 59.72% using the 10-fold cross-validation on balanced positive and negative samples. A feature analysis showed that all features applied in this method contributed to the acetylation process. A position-specific analysis showed that the features derived from the critical neighboring residues contributed profoundly to the acetylation site determination. The detailed analysis in this paper can help us to understand more of the acetylation mechanism and can provide guidance for the related experimental validation.

Osteoporosis (OP) is characterized by low bone mineral density (BMD) and has strong genetic determination. However, specific genetic variants influencing BMD and contributing to pathogenesis of osteoporosis are largely uncharacterized. Current genetic studies in bone filed, which aimed at identification of OP risk genes, are mostly focused on DNA, RNA, or protein level individually, lacking integrative evidences from the three levels of genetic information flow to confidently ascertain the significance of genes for osteoporosis. Our previous proteomics study discovered that superoxide dismutase 2 (SOD2) in circulating monocytes (CMCs, i.e., potential osteoclast precursors) was significantly up-regulated at protein level in vivo in Chinese with low vs. high hip BMD. Herein, at mRNA level, we found that SOD2 gene expression was also up-regulated in CMC (p < 0.05) in Chinese with low vs. high hip BMD. At DNA level, in 1,627 unrelated Chinese subjects, we identified eight SNPs at SOD2 gene locus that were suggestively associated with hip BMD (peak signal at rs11968525, p = 0.048). Among the eight SNPs, three SNPs (rs7754103, rs7754295, and rs2053949) were associated with SOD2 mRNA expression level (p < 0.05), suggesting that they are expression quantitative trait locus (eQTL) regulating SOD2 gene expression. In conclusion, the present integrative evidences from DNA, RNA, and protein levels supported SOD2 as a susceptibility gene for osteoporosis.

Background

Internal medicine includes several subspecialties. This study aimed to describe change trend of impact factors in different subspecialties of internal medicine during the past 12 years, as well as the developmental differences among each subspecialty, and the possible influencing factors behind these changes and differences.

Methods

Nine subspecialties of internal medicine were chosen for comparison. All data were collected from the Science Citation Index Expanded and Journal Citation Reports database.

Results

(1) Journal numbers in nine subspecialties increased significantly from 1998 to 2010, with an average increment of 80.23%, in which cardiac and cardiovascular system diseases increased 131.2% rank the first; hematology increased 45% rank the least. (2) Impact Factor in subspecialties of infectious disease, cardiac and cardiovascular system diseases, gastroenterology and hepatology, hematology, endocrinology and metabolism increased significantly (p<0.05), in which gastroenterology and hepatology had the largest increase of 65.4%. (3) Journal impact factor of 0–2 had the largest proportion in all subspecialties. Among the journals with high impact factor (IF>6), hematology had the maximum proportion of 10%, nephrology and respiratory system disease had the minimum of 4%. Among the journal with low impact factor (IF<2), journal in nephrology and allergy had the most (60%), while endocrinology and metabolism had the least (40%). There were differences in median number of IF among the different subspecialties (p<0.05), in which endocrinology and metabolism had the highest, nephrology had the lowest. (4) The highest IF had a correlation with journal numbers and total paper numbers in each field.

Conclusion

The IF of internal medicine journals showed an increasingly positive trend, in which gastroenterology and hepatology increase the most. Hematology had more high IF journals. Endocrinology and metabolism had higher average IF. Nephrology remained the lowest position. Numbers of journals and total papers were associated with the highest IF.

Introduction

Human height is a highly heritable trait considered as an important factor for health. There has been limited success in identifying the genetic factors underlying height variation. We aim to identify sequence variants associated with adult height by a genome-wide association study of copy number variants (CNVs) in Chinese.

Methods

Genome-wide CNV association analyses were conducted in 1,625 unrelated Chinese adults and sex specific subgroup for height variation, respectively. Height was measured with a stadiometer. Affymetrix SNP6.0 genotyping platform was used to identify copy number polymorphisms (CNPs). We constructed a genomic map containing 1,009 CNPs in Chinese individuals and performed a genome-wide association study of CNPs with height.

Results

We detected 10 significant association signals for height (p<0.05) in the whole population, 9 and 11 association signals for Chinese female and male population, respectively. A copy number polymorphism (CNP12587, chr18:54081842-54086942, p = 2.41×10−4) was found to be significantly associated with height variation in Chinese females even after strict Bonferroni correction (p = 0.048). Confirmatory real time PCR experiments lent further support for CNV validation. Compared to female subjects with two copies of the CNP, carriers of three copies had an average of 8.1% decrease in height. An important candidate gene, ubiquitin-protein ligase NEDD4-like (NEDD4L), was detected at this region, which plays important roles in bone metabolism by binding to bone formation regulators.

Conclusions

Our findings suggest the important genetic variants underlying height variation in Chinese.

The tumor suppressor candidate gene RASSF1A encodes a microtubule-associated protein that is implicated in the regulation of cell proliferation, migration, and apoptosis. Several studies indicate that down-regulation of RASSF1A resulting from promoter hypermethylation is a frequent epigenetic abnormality in malignant melanoma. In this study, we report that compared with melanocytes in normal skins or benign skin lesions, RASSF1A is down-regulated in melanoma tissues as well as cell lines, and its expression negatively correlates with lymph node metastasis. Following ectopic expression in RASSF1A–deficient melanoma A375 cell line, RASSF1A reduces cell viability, suppresses cell cycle progression but enhances apoptotic cell death. In vivo, RASSF1A expression inhibits the tumorigenic potential of A375 cells in nude mice, which also correlates with decreased cell proliferation and increased apoptosis. On the molecular level, ectopic RASSF1A expression leads to differential expression of 209 genes, including 26 down-regulated and 183 up-regulated ones. Among different signaling pathways, activation of the apoptosis signal-regulating kinase 1 (ASK1)/p38 MAP kinase signaling is essential for RASSF1A-induced mitochondrial apoptosis, and the inhibition of the Akt/p70S6 kinase/eIF4E signaling is also important for RASSF1A-mediated apoptosis and cell cycle arrest. This is the first study exploring the biological functions and the underlying mechanisms of RASSF1A during melanoma development. It also identifies potential targets for further diagnosis and clinical therapy.

Background

HIV testing is still stigmatized among many high-risk groups in China while routine syphilis testing has been widely accepted at STI clinics. This project used the platform of a rapid syphilis screening test to expand HIV test uptake. The objective of this study was to use multilevel modeling to analyze determinants of syphilis and HIV testing uptake at STI clinics in China.

Methods

2061 STI patients at six clinics in Guangdong Province were offered free rapid syphilis and free rapid HIV testing. Test uptake was defined by patient receipt of results and a multilevel model was used to analyze predictors of uptake.

Results

This was the first syphilis or HIV test for the large majority (1388, 77.7%) of participants. Syphilis test uptake and HIV test uptake were high (1681, 81.6%, syphilis test uptake; 1673, 81.2% HIV test uptake). HIV test uptake was significantly concordant with syphilis test uptake (τb = 0.89, p < 0.001). The most parsimonious model of HIV test refusal included the following variables: being married, having a previous HIV test, being unaccompanied, and participating in the last two months of the study.

Conclusions

STI-clinic based screening for syphilis and HIV represents an excellent opportunity for scaling up integrated services, especially in South China where syphilis and sexually transmitted HIV cases are both rapidly increasing. Effective integration of HIV testing into routine clinical practice requires an understanding not only of individual test uptake but also of the broader social context of HIV testing.

Background and methods

Paclitaxel, a widely used antitumor agent, has limited clinical application due to its hydrophobicity and systemic toxicity. To achieve sustained and targeted delivery of paclitaxel to tumor sites, liposomes composed of egg phosphatidylcholine, cholesterol, and distearolyphosphatidyl ethanolamine-N-poly(ethylene glycol) (PEG2000) were prepared by a lipid film method. In addition, the liposomes also contained truncated fibroblast growth factor fragment-PEG-cholesterol as a ligand targeting the tumor marker fibroblast growth factor receptor. Physicochemical characteristics, such as particle size, zeta potential, entrapment efficiency, and release profiles were investigated. Pharmacokinetics and biodistribution were evaluated in C57BL/6 J mice bearing B16 melanoma after intravenous injection of paclitaxel formulated in Cremophor EL (free paclitaxel), conventional liposomes (CL-PTX), or in targeted PEGylated liposomes (TL-PTX).

Results

Compared with CL-PTX and free paclitaxel, TL-PTX prolonged the half-life of paclitaxel by 2.01-fold and 3.40-fold, respectively, in plasma and improved the AUC0→t values of paclitaxel by 1.56-fold and 2.31-fold, respectively, in blood. Biodistribution studies showed high accumulation of TL-PTX in tumor tissue and organs containing the mononuclear phagocyte system (liver and spleen), but a considerable decrease in other organs (heart, lung, and kidney) compared with CL-PTX and free paclitaxel.

Conclusion

The truncated fibroblast growth factor fragment-conjugated PEGylated liposome has promising potential as a long-circulating and tumor-targeting carrier system.