The clinical significance of and the factors associated with macrolide resistance and poor macrolide response in pediatric Mycoplasma pneumoniae infection: A retrospective study.

BACKGROUND: Macrolide-resistant Mycoplasma pneumoniae (MRMP) infection is increasing worldwide. However, its clinical significance is still uncertain. METHODS: The data of the Laboratory Medicine Department of Chang Gung Memorial Hospital in northern Taiwan was searched for children with molecular confirmed macrolide-susceptible Mycoplasma pneumoniae (MSMP) and MRMP infections between January 2011 and December 2018. The clinical features, laboratory data, and chest image presentations were compared between patients with MRMP and MSMP infections and between patients with good and poor macrolide response, respectively. RESULTS: Records from 158 patients were recovered. Of the enrolled patients 34 (22%) suffered MRMP infection, 27 (17%) had pleural effusions, and 47 (32%) had poor macrolide response. The macrolide resistance rate was 12% in 2011, 20% between 2015 and 2016, and 50% between 2017 and 2018, respectively. Other than a poor macrolide response, the MRMP and MSMP infections are clinically indistinguishable. The presence of pleural effusion and MRMP infections were found to be independently associated with a poor macrolide response, with odds ratios (95% confidence interval) of 14.3 (4.9-42.0) and 14.6 (5.4-40), respectively. The macrolide resistance rate of the patients with a poor macrolide response was 49% and 18% among all the patients enrolled and the patients with a pleural effusion, respectively. CONCLUSION: The macrolide resistance rate had possibly increased in recent years in Taiwan and should be continuously monitored. In addition, the macrolide response could be misleading in predicting a macrolide resistance especially for the patients with a pleural effusion.

Characterization of Hepatitis B Virus in Tenofovir-Treated and Untreated Chronically Infected Mothers and Their Immunoprophylaxis Failure Infants.

BACKGROUND: Maternal tenofovir disoproxil fumarate (TDF) therapy during late pregnancy can reduce mother-to-infant transmission of hepatitis B virus (HBV). We investigated HBV mutations associated with maternal TDF therapy and their role in infant immunonophylaxis failure (IPF). METHODS: Serum samples from untreated (n = 89) and TDF-treated (n = 68), highly viremic, chronically infected mothers and their infants were analyzed for HBV DNA by nested polymerase chain reaction (PCR) and direct sequencing. RESULTS: At delivery, compared with untreated mothers, TDF-treated mothers had a lower HBV DNA titer and a higher frequency of basal core promoter (BCP) gene mutations, but they had similar frequencies in pre-S/S and pre-core/core mutations. The 14 mothers harboring surface "a" determinant mutants did not transmit the mutants to their immunized infants. Such mutants were found in 3 of 13 IPF infants; the 13 mothers had wild-type hepatitis B surface antigen (HBsAg). In univariable analysis, maternal HBV DNA titer (odds ratio [OR]: 1.54; 95% confidence intervals [CI]: 1.02-2.33; P = .039), genotype C (OR: 4.18; 95% CI: 1.28-13.62; P = .018) and pre-S1 wild-type sequence (OR: 6.33; 95% CI: 1.85-21.68; P = .003) at delivery were associated with infant IPF. Multivariable analyses showed that maternal genotype C (OR: 3.71; 95% CI: 1.11-12.36; P = .033) and pre-S1 wild-type (OR: 6.34; 95% CI: 1.79-22.44; P = .004) were associated with infant IPF independently of maternal viremia. CONCLUSIONS: Along with high maternal HBV DNA titer at delivery, maternal genotype C and pre-S1 wild-type sequence were potential risk factors for infant IPF, although BCP mutations were not. The offspring of pregnant women harboring "a" determinant mutants as major strains seemed to be protected by immunoprophylaxis. CLINICAL TRIALS REGISTRATION: NCT01312012.

Delivery management of suspected or confirmed COVID-19 positive mothers.

The Coronavirus Disease-2019 (COVID-19) pandemic has brought catastrophic impact on the world since the beginning of December 2019. Extra precautionary measures against COVID-19 during and after delivery are pivotal to ensure the safety of the baby and health care workers. Based on current literature, it is recommended that delivery decisions be discussed between obstetricians and neonatologists prior to delivery, and designated negative pressure delivery rooms should be arranged for COVID person under investigation (PUI). During delivery, a minimal number of experienced staff attending delivery should don personal protective equipment (PPE) and follow the neonatal resuscitation program (NRP). Positive pressure ventilation is best used in a negative pressure room if available. At-risk babies should be transported in an isolette, and tested for COVID-19 in a negative pressure room soon after bathing. Skin-to-skin contact and breast milk feed should continue under certain circumstances. Although newborns with COVID-19 infections often present with symptoms that mimic sepsis and one third of affected patients may demand some form of respiratory support, short-term prognoses are favorable and most recover within two weeks of symptoms onset. In this article, we will further elaborate on topics covering timing and mode of delivery, antenatal steroid, vertical transmission, delivery room management, airway management, transport, testing and isolation after birth, skin-to-skin contact, breast milk feeding, clinical features, outcomes, and discharge plans. In addition, we also share our experiences of encountering neonates born of suspected COVID-19 positive mothers.

Breastfeeding in Relation to Neonatal Jaundice in the First Week After Birth: Parents' Perceptions and Clinical Measurements.

Background: Parents may consider interrupting breastfeeding to manage neonatal jaundice (NJ). Our aims were to determine correlations of breastfeeding with NJ by examining infants' manifestations in the first week after birth and to understand parents' perceptions toward NJ in relation to breastfeeding. Materials and Methods: This prospective cross-sectional study was conducted in a tertiary medical center by examining infants and administering a questionnaire survey to their parents. All healthy infants admitted to the well-baby nursery were eligible for enrollment. A 16-item questionnaire was distributed to parents of enrolled infants from October 2017 to February 2019. Items of the questionnaire included perceptions and knowledge of NJ. In addition, clinical information of enrolled infants was obtained from medical records. Hyperbilirubinemia was defined as a peak transcutaneous bilirubinometer value ≥15 mg/dL. Results: In total, 449 parents completed the consent form and participated in the study. Results showed that exclusive breastfeeding was more common in infants with a vaginal delivery (p < 0.001), who were nonprimiparous (p = 0.004) and who had weight loss of >7% (p < 0.001). There was no significant correlation of exclusive breastfeeding with hyperbilirubinemia (p = 0.414). Approximately two-thirds of parents were worried about NJ occurring in their child. Most parents were aware of phototherapy as management of NJ. However, their knowledge of risk factors, complications, and assessments of NJ was relatively deficient. Overall, 29.6% of parents rated breastfeeding as a risk factor for NJ, and 24% of parents indicated that cessation of breastfeeding was a management option for NJ. Conclusions: The results indicated that NJ in the first few days after birth poses a significant barrier to breastfeeding. Our findings provide critical information for plotting strategies to enhance parents' willingness to continue breastfeeding.

Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis.

The hydroxylase cytochrome P450 1A1 (CYP1A1) is regulated by the inflammation-limiting aryl hydrocarbon receptor (AhR), but CYP1A1 immune functions remain unclear. We observed CYP1A1 overexpression in peritoneal macrophages (PMs) isolated from mice following LPS or heat-killed Escherichia. coli (E. coli) challenge. CYP1A1 overexpression augmented TNF-α and IL-6 production in RAW264.7 cells (RAW) by enhancing JNK/AP-1 signalling. CYP1A1 overexpression also promoted 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) production in activated RAW, while a 12(S)-HETE antibody attenuated and 12(S)-HETE alone induced inflammatory responses. Macrophages harbouring hydroxylase-deficient CYP1A1 demonstrated reduced 12(S)-HETE generation and LPS-induced TNF-α/IL-6 secretion. CYP1A1 overexpression also impaired phagocytosis of bacteria via decreasing the expression of scavenger receptor A (SR-A) in PMs. Mice injected with CYP1A1-overexpressing PMs were more susceptible to CLP- or E. coli-induced mortality and bacteria invading, while Rhapontigenin, a selective CYP1A1 inhibitor, improved survival and bacteria clearance of mice in sepsis. CYP1A1 and 12(S)-HETE were also elevated in monocytes and plasma of septic patients and positively correlated with SOFA scores. Macrophage CYP1A1 disruption could be a promising strategy for treating sepsis. Video abstract.

Correction to: Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis.

An amendment to this paper has been published and can be accessed via the original article.

Risk assessment of prolonged jaundice in infants at one month of age: A prospective cohort study.

Prolonged jaundice is a commonly evaluated condition. The aim of this study was to assess the risk factors of jaundice in healthy infants at one month of age. This prospective cohort study enrolled 509 healthy infants from 2013 to 2018. Those with gestational age (GA) less than 35 weeks, birth weight less than 2000 grams, and illness were not enrolled. Jaundice was defined as a transcutaneous bilirubin value ≥5 mg/dL at 25-45 days of age. Umbilical cord blood samples were obtained to examine seven common gene variants. The incidence of prolonged jaundice was 32.2%. Prolonged jaundice was more common in infants with exclusive breastfeeding (p < 0.001), GA 35~37 w (p = 0.001), stool passage >4 times/d (p < 0.001), previous phototherapy (p < 0.001), and gene variant of G to A at nt 211 of UGT1A1 (p = 0.004). A multivariate logistic regression analysis demonstrated the greatest risk for prolonged jaundice was exclusive breastfeeding (OR = 2.818, 95% CI = 1.851-4.292), followed by previous phototherapy (OR = 2.593, 95% CI = 1.716-3.919), GA 35~37 w (OR = 2.468, 95% CI = 1.350-4.512), and G to A at nt 211 of UGT1A1 (OR = 1.645, 95% CI = 1.070-2.528). In conclusion, infants with exclusive breastfeeding, GA 35~37 w, previous phototherapy, or G to A at nt 211 of UGT1A1 are at greater risk of prolonged jaundice. Healthcare professionals should consider these risk factors in their assessment of prolonged jaundice.

Research progress on osteoarthritis treatment mechanisms.

Osteoarthritis is a common disease and is frequently encountered in the older population; the incidence rises sharply with age. It is estimated that more than 360 million people suffer from OA. However, the pathogenesis of osteoarthritis remains unclear, and we cannot effectively prevent the progression of OA. The aim of this review was to explore the molecular markers and signaling pathways that induce chondrocyte apoptosis in OA. We searched, using the key words osteoarthritis, chondrocyte apoptosis, autophagy, endoplasmic reticulum stress, molecular targets, and biomarkers, in PubMed, Web of Science, and Google Scholar from 1994 to 2017. We also reviewed the signaling pathways and molecular markers associated with chondrocyte apoptosis and approaches aimed at inhibiting the apoptosis-inducing mechanism to at least delay the progression of cartilage degeneration in OA. This article provides an overview of targeted therapies and the related signaling pathways in OA.

Comparative Survey of Holding Positions for Reducing Vaccination Pain in Young Infants.

Background. Infant holding position may reduce vaccination pain. However, the optimal position for young infants remains controversial. Objectives. To compare the effectiveness of holding infants in the supine position and the effectiveness of holding infants in upright position for relieving acute pain from vaccine injection. Methods. This prospective cohort study enrolled 6-12-week-old healthy infants. We examined infant pain responses by evaluating the following three categories: (1) crying, (2) irritability, and (3) facial expression. Results. In total, 282 infants were enrolled, with 103 and 179 held in the supine and upright positions, respectively. At 30 s after vaccination, the infants in the supine position showed a larger decrease in crying (p < 0.001), irritability (p = 0.002), and pained facial expression (p = 0.001) than did those in the upright position. However, there was no significant difference in pain response between two groups at 180 s after intervention. Conclusion. In 2-month-old infants, the supine position may reduce acute pain more effectively than does the upright position. Our findings provide a clinical strategy for relieving vaccination pain in young infants.

Comparison of iatrogenic pain between rotavirus vaccination before and after vaccine injection in 2-month-old infants.

Oral rotavirus vaccine (RV) administration in conjunction with other injectable vaccines has been used worldwide. However, whether the sequence of RV administration is associated with the reduction of injection-induced pain remains unclear. In this randomized controlled trial, we enrolled 6-12-wk-old healthy infants. The pain response of the infants was scored on the basis of their crying, irritability, facial expression, gagging and distress. A multivariate logistic regression model was used to compare the pain response after adjustment for possible confounders. We enrolled 352 infants, of whom 176 infants received RV before injection (experimental group) and 176 infants received an RV after injection (comparison group). Sex, number of injections, main caregiver, feeding type, and RV type did not differ significantly between the 2 groups. Multivariate regression analyses showed that, at 30 s after the intervention, the episode of gagging was more frequent in the comparison group than in the experimental group (p = 0.004). At 180 s after the intervention, the infants cried more often in the comparison group (p < 0.001). Furthermore, the infants in the experimental group more often relaxed (p < 0.001), rested quietly (p = 0.001), and were smiling (p = 0.001) than did those in the comparison group. Our results indicate that compared with oral RV administration after injection, oral RV administration before injection is more effective in reducing injection-induced pain in 2-mo-old infants. The findings can provide a clinical strategy for relieving pain from vaccination in young infants.

Risk assessment of gene variants for neonatal hyperbilirubinemia in Taiwan.

BACKGROUND: Hyperbilirubinemia is a common disorder during neonatal period in Taiwan. Gene variants may play an important role in the development of neonatal hyperbilirubinemia. The current study investigated the association between neonatal hyperbilirubinemia and common gene variants involving the production and metabolism of bilirubin. METHODS: This prospective study enrolled 444 healthy infants born in the Chang Gung Memorial Hospital at Taipei from 2013-2015. Hyperbilirubinemia was defined as a total bilirubin ≥ 15 mg/dL. A log-binomial model was used to assess the risk of gene variants. RESULTS: The most common genetic variant was short heme oxygenase (HO)-1 promoter GT-allele (<24 repeats) (39.4 %), followed by GA at nt388 in hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) (31.1 %), GA at nt211 in UDP-glucuronosyltransferase 1A1 (UGT1A1) (29.3 %), ABO incompatibility (16.2 %), alpha thalassemia (5.0 %), and G6PD deficiency (3.2 %). The log-binomial analysis demonstrated greater risks of hyperbilirubinemia in infants with GA at nt211 in UGT1A1 (RR = 1.548; 95 % CI = 1.096-2.187), short HO-1 promoter GT-repeat (RR = 2.185; 95 % CI = 1.527-3.125), and G6PD deficiency (RR = 1.985; 95 % CI = 1.010-3.901). The other gene variants - including blood type, alpha thalassemia, and SLCO1B1 - carried no significant risk. CONCLUSIONS: G6PD deficiency, short HO-1 promoter GT-repeat and GA at nt211 in UGT1A1 are risk factors of neonatal hyperbilirubinemia. The data provide clinical evidence to explain the high incidence of neonatal hyperbilirubinemia in Taiwan.

Effect of partial splenic embolization on the immune function of cirrhosis patients with hypersplenism.

OBJECTIVE: To discover the effect of partial splenic embolization on the immune function of cirrhotic patients with hypersplenism. METHODS: Patients involved in the study were enrolled and divided into three groups, including control group, experimental group, and complication group. Numbers of CD3(+), CD4(+) and CD8(+) T cells and CD4(+)CD25(+)CDl27(low/-) Treg cells in the peripheral blood of patients before surgery, 1 month, 6 months, 1 year, and 2 years after surgery were analyzed by fluorescence active cell sorting (FACS). Contents of immunoglobulins (IgA, IgG and IgM) were analyzed by auto immunoassay analyzer. RESULTS: In the peripheral blood of patients from experimental group, numbers of CD3(+), CD4(+) and CD8(+) T cells initially declined, but afterwards increased to normal level; in the peripheral blood of patients from complication group, CD3(+) and CD8(+) T cells showed the same trend, but the number of CD4(+) T cells was below normal level at all detection times. Furthermore, CD3(+), CD4(+) and CD8(+) T cells in the peripheral blood of patients from complication group were initially less than those in experimental group, and afterwards were comparable between two groups. In patients from both experimental group and complication group, the number of CD4(+) CD25(+) CDl27(low/-)Treg cells increased 1 month and 6 months after surgery, and gradually restored to normal level. CD4(+)CD25(+)CDl27(low/-) Treg cell counts in patients from complication group were initially more than those in patients from experimental group 1 month and 6 months after surgery, but then they were comparable. Furthermore, contents of immunoglobulins (IgA, IgG and IgM) were comparable in three groups at all detection times. CONCLUSION: Partial splenic embolization influenced the immune function of cirrhotic patients with hypersplenism in the short term but the immune function could afterwards gradually restore to normal. Our results implicated that measures that prevent infection and improve immune function were necessary in early stage after undergoing PSE in order to reduce complications.

Stool fatty acid soaps, stool consistency and gastrointestinal tolerance in term infants fed infant formulas containing high sn-2 palmitate with or without oligofructose: a double-blind, randomized clinical trial.

BACKGROUND: Formula-fed (FF) infants often have harder stools and higher stool concentrations of fatty acid soaps compared to breastfed infants. Feeding high sn-2 palmitate or the prebiotic oligofructose (OF) may soften stools, reduce stool soaps, and decrease fecal calcium loss. METHODS: We investigated the effect of high sn-2 palmitate alone and in combination with OF on stool palmitate soap, total soap and calcium concentrations, stool consistency, gastrointestinal (GI) tolerance, anthropometrics, and hydration in FF infants. This double-blind trial randomized 165 healthy term infants 25-45 days old to receive Control formula (n = 54), formula containing high sn-2 palmitate (sn-2; n = 56), or formula containing high sn-2 palmitate plus 3 g/L OF (sn-2+OF; n = 55). A non-randomized human milk (HM)-fed group was also included (n = 55). The primary endpoint, stool composition, was determined after 28 days of feeding, and was assessed using ANOVA accompanied by pairwise comparisons. Stool consistency, GI tolerance and hydration were assessed at baseline, day 14 (GI tolerance only) and day 28. RESULTS: Infants fed sn-2 had lower stool palmitate soaps compared to Control (P = 0.0028); while those fed sn-2+OF had reduced stool palmitate soaps compared to both Control and sn-2 (both P < 0.0001). Stool total soaps and calcium were lower in the sn-2+OF group than either Control (P < 0.0001) or sn-2 (P < 0.0001). The HM-fed group had lower stool palmitate soaps, total soaps and calcium (P < 0.0001 for each comparison) than all FF groups. The stool consistency score of the sn-2+OF group was lower than Control and sn-2 (P < 0.0001), but higher than the HM-fed group (P < 0.0001). GI tolerance was similar and anthropometric z-scores were <0.2 SD from the WHO growth standards in all groups, while urinary hydration markers were within normal range for all FF infants. CONCLUSIONS: Increasing sn-2 palmitate in infant formula reduces stool palmitate soaps. A combination of high sn-2 palmitate and OF reduces stool palmitate soaps, total soaps and calcium, while promoting softer stools. TRIAL REGISTRATION: This study was registered on http://www.clinicaltrials.gov: number NCT02031003.

[Application of propofol sedation in patients undergoing continuous venous-venous haemodiafiltration].

OBJECTIVE: To study the use of propofol sedation in patients undergoing continuous venous-venous haemodiafiltration (CVVHDF) and assess the curative effects. METHODS: A retrospective study was conducted. Data from 74 patients with continuous sedation of propofol in emergency intensive care unit (ICU) from April 2009 to June 2011 were analyzed. There were 26 cases suffering from acute renal failure in CVVHDF group and 48 critical cases in non-CVVHDF group. Propofol administration duration, dose, the clearance rate and the average recovery time in both groups were analyzed, and plasma concentrations of propofol at inflow side and outflow side of CVVHDF circuit in 26 patients with CVVHDF were determined. RESULTS: Compared with non-CVVHDF group, it took a longer administration time (298.37±28.73 hours vs. 173.44±17.27 hours, P<0.05) and higher dose (35.89±0.76 g vs. 21.82±0.62 g, P<0.05) in CVVHDF group. There were no statistical significances on clearance rate at 2, 6, 24 hours after administration (2 hours: 13.85±1.15 ml/min vs. 14.41±1.21 ml/min, 6 hours: 5.92±0.52 ml/min vs. 6.32±0.59 ml/min, 24 hours: 4.75±0.41 ml/min vs. 5.33±0.45 ml/min) and recovery time (8.89±1.46 minutes vs. 8.47±1.37 minutes) between CVVHDF and non-CVVHDF groups (all P>0.05). Plasma concentrations of propofol at inflow side and outflow side of CVVHDF circuit were not different after propofol administration in 26 CVVHDF patients. CONCLUSIONS: Compared with patients in non-CVVHDF group, the patients who received propofol in CVVHDF required higher total dosage and longer delivery time to maintain a good sedation. In both two groups clearance rate of propofol and maintenance of a stable blood concentration were the same. The use of a proper dose of propofol in CVVHDF did not affect wake up time of the patients, there were no complications.

Characteristics of the first human milk bank in Taiwan.

BACKGROUND: The benefits of feeding human milk to infants, even in prematurity, have been well documented. Well-organized donor milk processing has made the milk bank a good source of nutrition for premature or sick infants if their own mother's milk is not sufficient or suitable. The Taipei City Hospital Milk Bank was established in 2005 and is the first nonprofit human milk bank to operate in Taiwan. METHODS: The milk bank has adopted standards of practice laid down by the Human Milk Banking Association of North America and United Kingdom Association for Milk Banking. The clinical characteristics of the eligible milk donors, the recipients, and the donor milk were reviewed retrospectively. RESULTS: In the past 6 years, 816 eligible donors donated a total or 13,900 L (mean 17.03 L/donor) of breast milk. The mean age of these donors was 31.3 years, and 79.7% of them had college education. Most had term delivery (91.2%), with mean birth weight of their babies being 3120 g; 68.9% of the donors were primiparas. A total of 551 infants had received bank milk, with these indications: prematurity (65.4%), malabsorption (7.6%), feeding intolerance (7.2%), maternal illness (5.1%) and post-surgery (4.6%). The pass rate of raw donor milk was around 72.1%. The most common reasons to discard raw milk were Gram-negative rods contamination (72.8%) and ≥10 colony-forming units/mL of coagulase-negative Staphylococcus (62.3%). Only 0.63% of donor milk post pasteurization showed bacterial growth. CONCLUSION: Proper management and operation of a human milk bank can support breastfeeding, and provide a safe alternative to artificial formula for feeding preterm or ill infants in Taiwan. Sustainability of the milk bank needs more propagation and financial support by health authorities.

Dose-dependent effects of nicotine on proliferation and differentiation of human bone marrow stromal cells and the antagonistic action of vitamin C.

A range of biological and molecular effects caused by nicotine are considered to effect bone metabolism. Vitamin C functions as a biological antioxidant. This study was to evaluate the in vitro effects of nicotine on human bone marrow stromal cells and whether Vitamin C supplementation show the antagonism action to high concentration nicotine. We used CCK-8, alkaline phosphatase (ALP) activity assay, Von Kossa staining, real-time polymerase chain reaction and Western Blot to evaluate the proliferation and osteogenic differentiation. The results indicated that the proliferation of BMSCs increased at the concentration of 50, 100 ng/ml, got inhibited at 1,000 ng/ml. When Vitamin C was added, the OD for proliferation increased. For ALP staining, we found that BMSCs treated with 50 and 100 ng/ml nicotine showed a higher activity compared with the control, and decreased at the 1,000 ng/ml. Bone morphogenetic protein-2 (BMP-2) expression and the calcium depositions decreased at 100 and 1,000 ng/ml nicotine, while the addition of Vitamin C reversed the down regulation. By real-time PCR, we detected that the mRNA expression of collagen type I (COL-I) and ALP were also increased in 50 and 100 ng/ml nicotine groups (P < 0.05), while reduced at 1,000 ng/ml (P < 0.05). When it came to osteocalcin (OCN), the changes were similar. Taken all together, it is found that nicotine has a two-phase effect on human BMSCs, showing that low level of nicotine could promote the proliferation and osteogenic differentiation while the high level display the opposite effect. Vitamin C could antagonize the inhibitory effect of higher concentration of nicotine partly.

Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-κB pathway.

Thymoquinone (TQ), the predominant bioactive constituent derived from the medicinal spice Nigella sativa (also known as black cumin), has been applied for medical purposes for more than 2,000 years. Recent studies reported that thymoquinone exhibited inhibitory effects on the cell proliferation of several cancer cell lines. This study was performed to investigate the antitumor and anti-angiogenic effects of thymoquinone on osteosarcoma in vitro and in vivo. Our results showed that thymoquinone induced a higher percentage of growth inhibition and apoptosis in the human osteosarcoma cell line SaOS-2 compared to that of control, and thymoquinone significantly blocked human umbilical vein endothelial cell (HUVEC) tube formation in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and western blot analysis, and found that thymoquinone significantly downregulated NF-κB DNA-binding activity, XIAP, survivin and VEGF in SaOS-2 cells. Moreover, the expression of cleaved caspase-3 and Smac were upregulated in SaOS-2 cells after treatment with thymoquinone. In addition to these in vitro results, we also found that thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing NF-κB and its regulated molecules. Collectively, our results demonstrate that thymoquinone effectively inhibits tumor growth and angiogenesis both in vitro and in vivo. Moreover, inhibition of NF-κB and downstream effector molecules is a possible underlying mechanism of the antitumor and anti-angiogenic activity of thymoquinone in osteosarcoma.

[Proliferation, differentiation and BMP-2 expression of osteoblasts cultured in the plane under suitable electrical stimulation].

OBJECTIVE: To observe proliferation and differentiation of osteoblasts cultured in the plane on appropriate electrical stimulation, to specify whether it promote the proliferation, and observe expression of BMP-2 on electrical stimulation. METHODS: Osteoblasts were extracted from the skull of rabbit offspring and cultured. Cells after the 2nd generations were cultured. In experimental group, cells had electrical stimulation, and same stimulation time and intensity were given. In control group cells had not electrical stimulation. The proliferation and differentiation were detected at different time, and BMP-2 protein expression was analyzed. RESULTS: The cell morphology of experimental group in 8 days under the light microscope was observed and showed a lot of proliferation of osteoblasts, pleomorphic changes, in 6 to 8 days a small amount of Calcified spots was also observed; while in the control group, proliferation was slower. Differentiation of the experimental group was significantly, alkaline phosphatase staining and calcium nodules were positive, quantitative analysis of alkaline phosphatase increaseed significantly. Experimental group showed that BMP-2 was gradually increased by immunohistochemistry analysis. CONCLUSION: Electrical stimulation can promote the proliferation and differentiation of osteoblasts and achieved the increasement the number of cells in short-term, intracellular staining by immunohistochemistry showed the increasement in expression of BMP-2.

Breast milk jaundice and maternal diet with chinese herbal medicines.

Our objective was to identify the association between maternal diet with Chinese herbal medicines and prolonged jaundice of breast-fed infants. Healthy infants at 25 to 45 days of age were eligible for enrollment into this prospective study. Jaundice was defined as a transcutaneous bilirubin (TcB) value ≥ 5 mg/dL. A questionnaire survey asking feeding type, stool pattern, and maternal diet was conducted at the time of TcB measurement. A total of 1148 infants were enrolled, including 151 formula-fed, 436 combination-fed, and 561 breast-fed infants. The incidences of jaundice were 4.0% in formula-fed infants, 15.1% in combination-fed infants, and 39.8% in breast-fed infants (P < 0.001). In addition, jaundice was noted in 37.1% of preterm infants and 25.0% of term infants (P < 0.001). Furthermore, jaundice was more common in breast-fed infants whose mothers did not consume the traditional Chinese herbal medicines than in breast-fed infants whose mothers did consume such medicines (P < 0.001). In conclusion, this cohort study has identified late-preterm birth and breast feeding as the contributory factors for prolonged jaundice of apparently well infants. The data indicate that postpartum diet with Chinese herbal medicines is associated with breast milk jaundice.

[Use of titanium elastic intramedullary nails in the treatment of adult midshaft clavicular fractures: technical skills, precautions and complications].

OBJECTIVE: To discuss surgical skills,precautions and complications of using titanium elastic intramedullary nails in the treatment of adult midshaft clavicular fractures and evaluate the therapeutic efficacy. METHODS: From June 2006 to January 2009, 28 patients with completely displaced midshaft clavicular fractures (15 simple fractures, 8 wedge fractures and 5 comminuted fractures) were enrolled in the study,included 19 males and 9 females with a mean age of 39.0 years (range 19-67 years). The injury was on the left side in 14 cases and on the right side in 14 cases. The mean course of disease was 2.9 days. The shoulders of the patients were swollen, deformed and disabled before operation. X-rays revealed complete displacement of the clavicle. The mean clavicular shortening after injury was 6.76% vs. that measured after bone healing. The Constant-Murley Shoulder Scoring System was used to assess shoulder function, and the DASH Score was used to assess the disability degree of the upper arm. RESULTS: Closed operation with titanium elastic intramedullary nails was undertaken in 26 cases, and open reduction was performed in the remaining two cases. Satisfactory reduction was achieved in all patients, who were followed up for a mean of 10 months (range 6-15 months). The mean union time was 11.5 weeks. No severe complication occurred in any patient. The mean clavicular shortening after bone healing was 3.38%, which was significantly different as compared with the mean clavicular shortening after injury. Constant-Murley Shoulder Score was (97.0 +/- 4.2), and DASH score was (3.4 +/- 4.8). Anatomical reduction, functional recovery and appearance were satisfactory in all patients. CONCLUSION: Treatment of adult midshaft clavicular fractures with titanium elastic intramedullary nails is advantageous and may prove to be an alternative option for nonsurgical treatment and plate osteosynthesis of midshaft clavicular fractures in adults.