LncRNA INHBA-AS1 promotes colorectal cancer cell proliferation by sponging miR-422a to increase AKT1 axis.

OBJECTIVE: In recent years, long non-coding RNAs (lncRNAs) have emerged for regulating the development, as well as progression in colorectal cancer (CRC), which assists in finding new targets for CRC treatment. A previous study indicated that INHBA-AS1 promotes oral squamous cell progression by sponging miR-143-3p. However, the exact function possessed by lncRNA INHBA-AS1 in CRC development remains unclear. PATIENTS AND METHODS: The expression level of INHBA-AS1 in CRC tissues and cell lines was determined by qRT-PCR. The functional role of INHBA-AS1 in CRC was investigated by a series of in vitro assays. RNA immunoprecipitation (RIP), bioinformatics analysis was utilized to explore the potential mechanisms of INHBA-AS1. RESULTS: The present study identified INHBA-AS1 as a kind of lncRNA with high expression in CRC tissues and cells. Functionally, NHBA-AS1 downregulation in CRC cells suppressed CRC cell proliferation as well as colony formability. Mechanistically, INHBA-AS1/miR-422a/AKT1 established the ceRNA network to regulate MMP-2, -7, -9 expressions that participated the modulation of CRC progression. CONCLUSIONS: In summary, LncRNA INHBA-AS1 contributes to CRC progression through AKT1 pathway, and provides a new mechanism to regulate CRC development, as well as a potential target for treating CRC.

[Advances in the research of stem cell tissue-engineering].

Recently, more and more researches use stem cells as seed cells. Three-dimensional culture and use of bioreactors can expand the scale of stem cells culture and increase the efficiency of culture, which can better simulate the microenvironment in vivo when combing cytokines, co-culture, biomaterials, or gene delivery to promote the directional tissue differentiation. In addition, in situ tissue regeneration technique can achieve tissue engineering in vivo for tissue repair and regeneration. This review elaborates advance of research in tissue engineering of stem cell in various aspects, and potential problems and challenges of tissue engineering of stem cell are discussed in depth.

[Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin in Asian adult patients with chronic HCV genotype 1b infection and compensated cirrhosis].

Objective: To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. Methods: An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. Results: A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. Conclusion: Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.

SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival.

Sperm-associated antigen 5 (SPAG5) is involved in various biological processes. However, the roles of SPAG5 in bladder urothelial carcinoma (BUC) are unknown. This study showed that upregulation of SPAG5 was detected frequently in primary BUC tissues, and was associated with significantly worse survival among the 112 patients that underwent radical cystectomy (RC). Up and downregulating the expression of SPAG5 enhanced or inhibited, respectively, the proliferation of BUC cells in vitro and in vivo, and suppressed or enhanced, respectively, apoptosis in vitro and in vivo. Moreover, SPAG5 increased the resistance of BUC cells to chemotherapy-induced apoptosis. Mechanistic investigations showed that SPAG5 promotes proliferation and suppresses apoptosis in BUC at least partially via upregulating Wnt3 through activating the AKT/mTOR signaling pathway. The importance of the SPAG5/AKT-mTOR/Wnt3 axis identified in BUC cell models was confirmed via immunohistochemical analysis of a cohort of human BUC specimens that underwent RC. Collectively, our data suggested that in patients with BUC who underwent RC, high SPAG5 expression is associated with poor survival. In addition, targeting SPAG5 might represent a novel therapeutic strategy to improve the survival of patients with BUC.

Impact Factors and Attitudes Toward Organ Donation Among Transplantation Patients and Their Caregivers in China.

PURPOSE: This study's purpose was to investigate the attitudes toward organ donation among renal transplantation patients and their caregivers. In addition, we sought to explore the impact factors that affect their attitudes toward deceased organ donation. DESIGN AND METHODS: A self-administrated questionnaire was used, which consisted of two parts: 1) demographic data, and 2) transplantation and donation-related data. This study was conducted in three transplantation follow-up centers in three hospitals using a cross-sectional approach. SPSS 17.0 software was used to analysis descriptive and inferential statistics for data. The responses were analyzed using descriptive statistics and logistic regression analysis. RESULTS: We received 426 effective questionnaires. The renal transplantation patients' mean age was 40.84 years. Among these patients, 67.8% were willing to accept the organ transplantation surgery for their relatives, 67.4% were willing to donate a living kidney to a close relative, 62.7% were willing to donate organs after death, 53.5% were willing to register in the national organ donation system, and 51.4% were willing to sign the organ donation consent when facing their relatives becoming a potential organ donor. Age, marriage status, education level, understanding of transplantation procedures and understanding of donation procedures had statistical significance in the difference of the attitudes toward donate their organs after death (P < .05). CONCLUSIONS: Renal transplantation patients in our study are more willing to donate organs after death than their caregivers, but both their attitudes toward deceased donation were not very optimistic. There is a significant relationship between participants' willingness and knowledge of organ donation; patients with more understanding of the transplantation and donation procedure were more willing to donate organs after death. Affected by traditional values such as Confucianism, many people still cannot accept registering in the national organ donation system or sign the organ donation consent when facing their relatives becoming potential organ donors. CLINICAL RELEVANCE: There is a need to give adequate training regarding donation to increase donation rates. The government must provide education from the perspective of scientific knowledge to change the traditional views of the public, which may then increase the donation rate in China.

Low miR-34c expression is associated with poor outcome in de novo acute myeloid leukemia.

INTRODUCTION: MicroRNA-34c (miR-34c) has been found to play important roles in tumorigenesis. However, little is known about miR-34c expression and the impact on prognosis in acute myeloid leukemia (AML). METHODS: Real-time quantitative PCR (qRT-PCR) was performed to analyze the status of miR-34c expression in 122 patients with de novo AML and 62 normal controls. RESULTS: MiR-34c expression in AML was significantly downregulated compared to controls (P < 0.001). Receiver operating characteristic curves (ROC) indicated the distinguishing value of miR-34c for discriminating whole-cohort AML, non-M3 AML, and cytogenetically normal AML (CN-AML) patients from healthy controls. No significant differences were found between low miR-34c-expressing and high miR-34c-expressing patients in age, sex, hemoglobin, platelet count, percentage of blasts in bone marrow (BM), WHO classifications, karyotypes, and eight gene mutations, but low miR-34c cases had higher white blood cells (WBC) than high miR-34c cases (P = 0.035). MiR-34c low-expressed patients had similar rates of complete remission (CR) as miR-34c high-expressed patients in whole-cohort AML, non-M3 AML, and CN-AML patients (P = 0.347, 0.314 and 0.167, respectively). Kaplan-Meier analysis indicated that patients with low miR-34c level had markedly shorter overall survival (OS) time in whole-cohort AML, non-M3 AML, and CN-AML patients (P = 0.033, 0.024 and 0.001, respectively). Furthermore, multivariate analysis confirmed that low miR-34c expression was an independent risk factor not only in whole-cohort AML (P = 0.040) but also in non-M3 AML (P = 0.015) and CN-AML patients (P = 0.021). CONCLUSIONS: Our findings indicate that low miR-34c level is a novel promising biomarker in predicting prognosis in patients with de novo AML.

[Venous-to-arterial carbon dioxide difference to arteriovenous oxygen content difference ratio combined with lactate to predict prognosis of patients with septic shock].

OBJECTIVE: To investigate the prognostic significance of venous-to-arterial carbon dioxide difference to arteriovenous oxygen content difference ratio (Pv-aCO2/Ca-vO2 ratio) combined with lactate in patients with septic shock during the early phases of resuscitation. METHODS: A retrospective study was conducted for 104 septic shock patients. All patients received an initial fluid resuscitation according to the Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012(SSC2012). Patients were classified into four groups according to lactate levels and Pv-aCO2/Ca-vO2 ratio at 6 h of resuscitation: group A, lactate≥2.0 mmol/L and Pv-aCO2/Ca-vO2>1.0; group B, lactate≥2.0 mmol/L and Pv-aCO2/Ca-vO2≤1.0; group C, lactate<2.0 mmol/L and Pv-aCO2/Ca-vO2>1.0; group D, lactate<2.0 mmol/L and Pv-aCO2/Ca-vO2≤1.0. The hemodynamic parameters and oxygen metabolism parameters were recorded at baseline and 6 h after fluid resuscitation. Sequential organ failure assessment (SOFA) score at day 1, day 3 were calculated. The 28-day mortality rate was recorded. RESULTS: (1) Group A had the highest SOFA score at day 3 and group D the lowest, which were respectively 10.8±3.3, 6.7±3.6, 5.6±3.1, 4.1±2.2 in four groups. Accordingly, the 28-day mortality rate of group A was the highest and group D the lowest, which were respectively 83.3%, 59.1%, 60.0%, 14.3% in four groups. The differences were statistically significant (P<0.05). (2) The Cox regression analysis of 28 d mortality revealed that lactate levels (RR=4.306, 95%CI 1.979-9.369) and Pv-aCO2/Ca-vO2 ratio (RR=2.888, 95%CI 1.676-4.976) at T6 were independent predictors to 28-day mortality. (3) The AUCROC of Pv-aCO2/Ca-vO2 ratio combined with lactate [0.910(95%CI 0.857-0.963)] was significantly greater than the AUCROC of wither lactate [0.762(95%CI 0.673-0.852), Z=2.775; P=0.006) or Pv-aCO2/Ca-vO2 ratio [0.781(95%CI 0.693-0.868), Z=2.458; P=0.014) alone. CONCLUSION: Combination of Pv-aCO2/Ca-vO2 ratio and lactate level at early stage of resuscitation in patients with septic shock is better than single parameter to predict the prognosis.

Mortality Predictors in Acute Respiratory Distress Syndrome Renal Transplant Recipients With ESKAPE/rESKAPE Pneumonia.

BACKGROUND: A sustained immunosuppressive state in renal transplant recipients is a factor that can contribute to increased incidence of acute respiratory distress syndrome (ARDS) due to pneumonia. ARDS renal recipients with ESKAPE (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp.) pneumonia are probably related to high morbidity and mortality. We therefore sought to investigate the frequency of ESKAPE and resistant ESKAPE (rESKAPE) pathogens isolated from respiratory tract specimens of renal recipients with ARDS and determine the risk factors for mortality. METHODS: A retrospective analysis of ARDS renal recipients with ESKAPE/rESKAPE pneumonia was reviewed. Multiple logistic regression analysis was conducted to identify the independent risk factors associated with infection-related mortality. RESULTS: During the study period, 88 ESKAPE pathogens obtained from respiratory tract specimens of 54 ARDS renal recipients were documented including 33 A. baumannii, 24 P. aeruginosa, 17 S. aureus, 6 K. pneumoniae, 8 Enterobacter species, and 0 E. Faecium. Among these ESKAPE organisms, 61.4% (54/88) were antimicrobial resistant. The risk factors for mortality independently associated with ARDS renal recipients with ESKAPE pneumonia were severe ARDS (odds ratio [OR] 4.3 (95% confidence interval [CI] 1.1-16.4), P = .032), serum creatinine level >1.5 mg/dL (OR 4.2 95% CI (1.0-17.9), P = .05) and body temperature less than 38°C (OR 5.0 (95% CI 1.3-19.6), P = .02) at ARDS onset. The independent determinants of mortality were associated with ARDS renal recipients with rESKAPE pneumonia were serum creatinine level >1.5 mg/dL (OR 13.7, 95% CI 1.3-142.1, P = .028) and body temperature less than 38°C (OR 5.5 (95% CI 1.1-26.6) at ARDS onset, P = .035). CONCLUSIONS: The majority of EPKAPE isolates were antimicrobial resistant. Mortality in ARDS renal recipients with ESKAPE/rESKAPE pneumonia was associated with the severity of ARDS, elevated serum creatinine level, or depressed febrile response at ARDS onset.

Association between the 8q24 rs6983267 T/G polymorphism and prostate cancer risk: a meta-analysis.

Recent studies have indicated that single nucleotide polymorphisms (SNPs) within the 8q24 region may be a risk factor for prostate cancer (PCa). Here, we performed a meta-analysis to evaluate the association between the 8q24 rs6983267 T/G polymorphism and PCa risk. A systematic literature search was carried out in multiple electronic databases independently by two investigators. Pooled odds ratios (ORs) and 95% confidence intervals for 8q24 rs6983267 T/G and PCa were calculated using a fixed-effect model (the Mantel-Haenszel method). In total, 24 case-control studies from 19 articles were included in our meta-analysis. Our analysis indicated that there is a significant PCa risk associated with the rs6983267 polymorphism in a dominant model (GG vs GT+TT, pooled OR = 1.298, P < 0.001); recessive model (GG+GT vs TT, pooled OR = 1.302, P < 0.001); and homozygote comparison (GG vs TT, pooled OR = 1.494, P < 0.001). Similarly, in a subgroup analysis of European and Asian descent, our results revealed that there are associations between rs6983267 T/G polymorphism and PCa susceptibility with the dominant model (GG vs GT+TT), recessive model (GG+GT vs TT), and homozygote comparison (GG vs TT). To investigate the association between rs6983267 and risk of PCa under different clinical conditions, further analyses were conducted regarding different clinical characteristics including the Gleason score, tumor stage, and PSA level to provide a more comprehensive view of PCa risk and this SNP. Publication bias was assed using the Begg test and the Egger test, and none was detected.

Frequency and clinical outcomes of ESKAPE bacteremia in solid organ transplantation and the risk factors for mortality.

BACKGROUND: Although bacteremias caused by the 6 ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have recently been highlighted as a serious complication in solid organ transplant (SOT), more information is urgently needed. We sought to investigate the frequency and clinical outcomes of ESKAPE bacteremia in SOT and determine the risk factors for mortality. METHODS: A retrospective analysis of bacteremia after SOT was reviewed. Risk factors for mortality caused by ESKAPE bacteremia were identified. RESULTS: Eighty-four episodes of bacteremia were caused by ESKAPE strains. Of these strains, 41 were caused by resistant ESKAPE (rESKAPE) organisms. The only factor for bacteremia-related mortality independently associated with ESKAPE was septic shock (odds ratio [OR] = 21.017, 95% confidence interval [CI] = 5.038-87.682, P < 0.001). The factors for bacteremia-related mortality independently associated with rESKAPE bacteremia were septic shock (OR = 16.558, 95% CI = 6.620-104.668, P = 0.003) and age ≥40 years (OR = 7.521, 95% CI = 1.196-47.292, P = 0.031). CONCLUSIONS: To improve the outcomes of transplantation, more effective therapeutic treatments are of paramount importance when older SOT recipients with bacteremia due to ESKAPE/rESKAPE organisms present with septic shock.

Mannose-binding lectin 2 and ficolin-2 gene polymorphisms influence the susceptibility to bloodstream infections in kidney transplant recipients.

INTRODUCTION: Both mannose-binding lectin (MBL) and ficolin (FCN) interact with carbohydrate structures on microbial surfaces. Polymorphisms at the promoter and exon 1 of the MBL2 gene, which are responsible for low serum levels of MBL, have been shown to play important roles to increase the risk of post-transplant infections. Three gene polymorphisms in the promoter region of FCN2 and 2 in exon 8 (+6424 G > T) are associated with serum levels of FCN2 or binding capacity toward N-acetylglucosamine on microbial surfaces. METHODS: We prospectively analyzed 81 kidney transplant recipients for 6 well-known functional single-nucleotide polymorphisms in the MBL2 and 5 in the FCN2 gene of the recipients determined by gene sequencing. The bloodstream infections collected prospectively were associated with MBL2 and FCN2 genotypic variants over the first year after kidney transplantation. RESULTS: Multivariate analyses only found an association of recipient QQ + PQ genotypes of MBL2 5'-UTR +4 (odds ratio [OR] = 3.677, 95% confidence intervals [CI] = 1.127-11.998, P = .031) and FCN2 exon 8 Thr 236 Met(+6359 C > T) (OR = 4.917, 95% CI = 1.229-19.667, P = .024) with the incidence of bacteremia. CONCLUSION: Recipient QQ + PQ genotypes of MBL2 5'-UTR +4 and recipient FCN2 exon 8 Thr 236 Met(+6359 C > T) variants showed significant impacts on the risk of developing bloodstream infections after kidney transplantation.

Genetic association of tumor necrosis factor-ß, interleukin-10, and interleukin-1 gene cluster polymorphism with susceptibility to pneumonia in kidney transplant recipients.

INTRODUCTION: Pneumonia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was therefore conducted to investigate whether or not the polymorphisms of tumor necrosis factor (TNF)ß, interleukin (IL)-10, IL-1ß, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to pneumonia within the first year after kidney transplantation. METHODS: Subjects comprised 33 kidney transplant recipients with pneumonia and 63 noninfected kidney transplant recipients. Genomic DNA from these 96 kidney transplant recipients was extracted from peripheral blood leukocytes. The regions containing the NcoI polymorphic site at position +252 of TNFß gene, the RsaI polymorphic site at position -592 of IL-10 gene, and the AvaI polymorphic site at position -511 of IL-1ß gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI, RsaI, and AvaI restriction enzyme, respectively. The polymorphic regions with intron 2 of the IL-1 ra gene (IL-1 RN) containing variable numbers of a tandem repeat of 86 base pairs, were amplified by PCR. RESULTS: Univariate analysis showed that recipient IL-10, IL-1ß, and IL-1 RN polymorphisms were not associated with the presence of pneumonia (P = .589, .940, and .286, respectively). However, compared with GG genotype, recipient TNFß +252AA + AG genotype was significantly associated with susceptibility to pneumonia (P = .006). Age of 45 years or older was not significantly associated with susceptibility to develop pneumonia but had a tendency to develop it (P = .119). After adjusting for age of 45 years or older, recipient TNFß+252 AA + AG genotype (odds ratio = 5.366, 95% confidence intervals = 1.470 - 19.589, P = .011) independently predicted the risk for pneumonia within the first year after kidney transplantation in the multivariate analysis. CONCLUSION: These results suggested that recipient TNFß gene polymorphism may be useful in predicting pneumonia, hence identifying individuals who could benefit from preventive treatment and a less potent immunosuppression regimen.

The risk factors for mortality in deceased donor liver transplant recipients with bloodstream infections.

BACKGROUND: Information on risk factors for mortality among deceased donor liver transplant recipients with bloodstream infections (BSIs) was sought using a retrospective analysis from January 2002 to January 2012. METHODS: We performed deceased donor liver transplantations in 135 subjects who experienced 77 episodes of BSIs. We assessed risk factors for mortality among 43 of them using univariate and multivariate logistic regression analysis. RESULTS: The 43 recipients (31.9%) who developed BSI showed a mean age of 45.1 (45.1 ± 14.1 years). The majority of infections were nosocomial in origin (97.7%), with more than half being polymicrobial (53.5%). There were 24 deaths among these recipients (55.8%). The univariate analysis identified the following variables as risk factors for BSI-related mortality: polymicrobial (P = .029), platelet count <50,000/mm(3) (P = .02), creatinine > 1.5 mg/dL (P = .008), and septic shock (P < .001). Multivariate logistic regression showed the independent risk factors for mortality to be a serum creatinine > 1.5 mg/dL and septic shock. CONCLUSION: The risk factors significantly associated with increased mortality in deceased donor liver transplant recipients with BSIs are higher serum creatinine levels and septic shock. Despite appropriate antimicrobial treatment, BSIs accompanied by septic shock or higher serum creatinine levels were associated with high mortality rates. It is therefore essential to protect renal function to reduce the incidence of BSIs.

Genetic association of interleukin-1ß (-511C/T) and its receptor antagonist (86-bpVNTR) gene polymorphism with susceptibility to bacteremia in kidney transplant recipients.

BACKGROUND: Bacteremia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was conducted to determine the influence of the polymorphisms of interleukin-1 ß (IL-1 ß) and IL-1 receptor antagonist gene (IL-1RN) on the susceptibility to bacteremia within the first year after kidney transplantation. METHODS: Twenty-one bacteremic and 60 noninfected kidney transplant recipients, underwent extraction genomic DNA, from peripheral blood leukocytes. The region containing the AvaI polymorphic site at position -511 of 1L-I ß gene was amplified by a polymerase chain reaction (PCR) and subsequently digested with AvaI restriction enzyme. The polymorphic regions within intron 2 of IL-1RN, containing variable numbers of a tandem repeat of 86 base pairs, were amplified by PCR. RESULTS: We observed greater frequency of the IL-1 ß -511CC genotype and IL-1 ß -511C allele among bacteremic versus noninfected recipients (P = .023 and P = .015, respectively). In contrast, the current study failed to show significant difference, either in genotypic or allelic frequency, for the IL-1RN polymorphisms regarding the incidence of bacteremia (P = .508 and P = .507, respectively). After adjustment we observed recipient IL-1 ß -511CC genotype (odds ratio [OR] = 4.400, 95% confidence interval [CI] = 1.517-12.759, P = .006) and recipient IL-1 ß-511C allele (OR = 2.444, 95% Cl = 1.172-5.100, P = .015) to predict independently the risk for bacteremia within the first year after kidney transplantation. CONCLUSION: The present work provided evidence that recipient IL-1 ß -511CC genotype or IL-1 ß -511C allele was associated with susceptibility to bacteremia within the first year after kidney transplantation. These results suggested that genotyping data may afford a more accurate prediction of bacteremia and the design of strategies to protect the most vulnerable patients.

Low-level prenatal lead exposure and neurobehavioral development of children in the first year of life: a prospective study in Shanghai.

We used a prospective study design to assess the effects of prenatal low-level lead exposure on the development of urban, inner-city children in Shanghai. Umbilical cord blood samples wee consecutively collected from 605 live newborns. Two hundred and fifty-seven samples were excluded from the study due to clotting. Lead levels were determined on 348 cord blood samples. The geometric mean was 9.2 micrograms/dl. Based on their cord blood lead levels, infants were classified into two exposure groups: 104 in a relatively low lead group (lead levels < or = 30 percentile), and 104 in a relatively high lead group (lead levels > or = 70 percentile). Seventy-five subjects failed to complete the study, and 133 babies were included in the final cohort: 69 babies in the high lead group and 64 in the low lead group. At 3, 6, and 12 months, the Bayley Scales of Infant Development were administered and capillary blood lead levels were measured. Detailed information was obtained on a wide range of variables relevant to infant development. At all three ages, the Mental Development index (MDI) scores, adjusted for confounders, were inversely related to the infants' cord blood lead levels. The difference of the mean adjusted MDI scores between low and high lead groups was 3.4 at 3 months, 6.3 at 6 months, and 5.2 at 12 months of age. These differences were statistically significant at all time points. No significant association between cord blood lead levels and the Psychomotor Development Index (PDI) scores was detected at all three visits after adjustment for confounders. Postnatal lead levels were unrelated to concurrent developmental status. We conclude that prenatal low-level lead exposure, which is relatively common in Shanghai, is associated with an adverse developmental impact on children through the first year of life.

Umbilical cord blood lead levels in Shanghai, China.

This study was designed to determine the cord blood lead (BPb) levels of babies born in one urban area of Shanghai, and to preliminarily identify the demographic, social environment and prenatal factors which have an effect on the cord BPb concentrations. From August to November 1993, umbilical cord blood samples were obtained from 605 live newborns in the Yangpu Maternal and Child Hospital. 257 samples were excluded from measurement because of clotting. In 348 cord samples, the geometric mean of cord BPb levels was 9.2 micrograms/dl, with a 95% confidence interval of the mean 8.86-9.54 (micrograms/dl). 142 babies (40.8%) had cord BPb levels of 10 micrograms/dl or greater. As a result of this high percentage of newborns with BPb levels equal to or greater than 10 micrograms/dl, we estimate that each year in the Shanghai City about 60,000 newborns are at risk for developing neuropsychological deficiencies caused by maternal lead exposure during pregnancy. To investigate the factors affecting cord blood levels, the subjects with levels greater than the 70th percentile (10.7 micrograms/dl) (n = 104) and less than the 30th percentile (7.4 micrograms/dl) (n = 104) were selected to compare the demographic, environment and prenatal medical history. Increased BPb levels at birth were associated with maternal passive smoking, a family member being occupationally exposed to lead, proximity to major traffic way, household coal combustion, neighborhood coal combustion, low level of maternal occupations, and the increasing occurrence of having the high lead foodstuff pidan (preserved duck egg) during pregnancy. We conclude that prenatal lead exposure has become an important health issue for young children in Shanghai.

Probing the determinants of disulfide stability in native pancreatic trypsin inhibitor.

The effects of single amino acid replacements on the stability of the 14-38 disulfide bond in the native form of bovine pancreatic trypsin inhibitor (BPTI) were measured. A total of 17 mutant proteins, with substitutions at one of 7 residues located 5-15 A from the disulfide in the native wild-type protein, were examined. The replacements were found to decrease the thermodynamic stability of the disulfide, as measured by exchange with thiol-disulfide reagents, by 0.6-5 kcal/mol, corresponding to a range of nearly 100 mV in redox potentials. The effects of the substitutions on disulfide stability were roughly correlated with the changes in side-chain volume, suggesting that optimal packing is a major factor in determining the stability of the disulfide in the wild-type protein. With only one exception, the substitutions also led to increases, as large as 50-fold, in the rates of disulfide reduction by dithiothreitol. The increased rates of reduction suggest that at least a fraction of the mutational destabilization of the disulfide is due to strain in the native protein that is relieved in the transition state for reduction. The stability of the disulfide in a peptide corresponding to the segments that are linked together by the 14-38 disulfide in native BPTI was found to be about 5 kcal/mol less than that of the disulfide in the intact wild-type protein. Together, the results with the mutant proteins and the peptide indicate that the stability of the disulfide in the native protein depends on both the local environment of the disulfide and on the ability of the rest of the protein to favor a conformation that promotes disulfide formation.

A comparative study of growth hormone (GH) and GH-releasing hormone(1-29)-NH2 for stimulation of growth in children with GH deficiency.

In this study, 60 patients with proven growth hormone deficiency (GHD) of hypothalamic origin were randomized into three equal groups, and received growth hormone-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2), 30 or 60 micrograms/kg/day, or growth hormone (GH), 0.1 IU/kg/day, for 6 months. There were no significant differences in growth between the two groups given GHRH(1-29)-NH2, but growth in the GH group was significantly better than in the other two groups (p < 0.01). Mean height velocities at 6 months were 9.2, 9.3 and 14.6 cm/year for the three groups, respectively. Plasma GHRH concentrations increased steadily over the 6-month treatment period, with higher levels in the group on the higher dose. During GHRH(1-29)-NH2 treatment, serum concentrations of insulin-like growth factor I rose initially, but then fell to values similar to those before treatment. No GH antibodies were detected, but all 20 patients on high-dose GHRH(1-29)-NH2 and 19 of 20 patients on low-dose GHRH(1-29)-NH2 developed GHRH antibodies. These had almost disappeared by 9 months after stopping treatment. There was no correlation between antibody titres and increase in height. No serious side-effects were seen, but three patients receiving GHRH(1-29)-NH2 reported mild irritation at the injection site. These results from the continuous infusion of GHRH(1-29)-NH2 over 6 months suggest that this treatment, or the related use of a depot preparation, is unlikely to be as effective as GH for the promotion of growth in GHD.

Growth promoting effect of zinc supplementation in infants of high-risk pregnancies.

This study was made to determine whether zinc deficiency is one of the factors involved in growth retardation of infants of high-risk pregnancies. The high risk factors were hypertension of pregnancy, diabetes mellitus, congenital heart disease, chronic nephritis, rheumatic heart disease and hyperthyroidism. 102 neonatal infants were divided into 3 groups: breast fed group, 37 cases; test group, 32 cases formula-fed with supplementary zinc 1.14-2.28 mg/kg/d; and control group, 33 cases formula-fed and supplemented with Vitamin B complex as placebo. The groups were divided by double-blind and randomized method. There were no differences in the 3 groups in sex ratio, growth status and serum zinc concentration at the beginning of the study. Anthropometric data were obtained at 0, 3 and 6 months.

The adverse effect of marginally higher lead level on intelligence development of children: a Shanghai study.

We surveyed 128 preschool children in a lead-polluted area in Shanghai to study the relationship between blood lead level and neuropsychological functions, assessed by age-appropriate psychological tests. The geometric means of blood lead level was 21.7 + -10.8 micrograms/dl. Of 47 children aged below 30 months, there was no significant difference in BSID indices between the high and low lead subjects, although the high lead children tended to have poorer development scores than the low lead ones. On the other hand, of 81 children older than 46 months, the WPPSI IQ scores showed highly significant negative correlation with blood lead level. Step-wise regression and multiple analysis of covariance techniques were employed to find out and control the confounding factors. Even when 21 non-lead variables were considered, the IQ difference between high and low lead groups remained statistically significant. We concluded that the children, especially those older than 46 months, in the area investigated, did suffer from lead toxicity causing impairment in intelligence development. We support the view that marginally higher lead level in children should be taken seriously.