[Risk factors for metabolic bone disease of prematurity in very/extremely low birth weight infants: a multicenter investigation in China].

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation (P < 0.05). Compared with the non-MBDP group, the MBDP group had significantly higher incidence rates of neonatal sepsis, anemia, hypocalcemia, and retinopathy of prematurity (P < 0.05). The MBDP group had a significantly lower mean feeding speed, a significantly higher age when reaching total enteral feeding, and a significantly longer duration of parenteral nutrition (P < 0.05). The use rate of caffeine citrate in the MBDP group was significantly higher, but the use rate of erythropoietin was significantly lower than that in the non-MBDP group (P < 0.05). The multivariate logistic regression analysis showed that gestational age < 32 weeks, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis were risk factors for MBDP (P < 0.05). CONCLUSIONS: A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

[A multicenter survey of antibiotic use in very and extremely low birth weight infants in Hunan Province].

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (rs=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (rs=0.196, P<0.01). CONCLUSIONS: Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.

21-gene recurrence score and adjuvant chemotherapy decisions in patients with invasive lobular breast cancer.

AIM: To determine the effect of the 21-gene recurrence score (RS) on outcome and chemotherapy decision in breast invasive lobular carcinoma (ILC). MATERIALS & METHODS: We included 6467 patients with early stage and estrogen receptor-positive ILC from the Surveillance, epidemiology, and end results database. RESULTS: A total of 9.1, 31.4, and 70.1% of patients with low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. A higher RS was independently associated with poor breast cancer-specific survival, and receipt of chemotherapy was not related to better breast cancer-specific survival in low-, intermediate-, or high-risk RS groups. CONCLUSION: The 21-gene RS could impact chemotherapy decision making in early-stage ILC. However, adjuvant chemotherapy does not appear to improve outcome in high-risk RS cohort.

Expression of pro-inflammatory cytokines in the auditory cortex of rats with salicylate-induced tinnitus.

Tinnitus often results in severe psychological distress. The present study hypothesized that tinnitus acts as a chronic stressor and induces dysregulation of the production of cytokines. The gap pre­pulse inhibition of acoustic startle paradigm was applied to test tinnitus­like behavior in rats. Following this, the mRNA and protein expression levels of interferon (IFN)­Î³, tumor necrosis factor (TNF)­α, interleukin (IL)­6 and N­methyl D­aspartate receptor subunit 2A (NR2A) were measured in rats subjected to acute and chronic salicylate treatment, using reverse transcription­quantitative polymerase chain reaction and western blot analysis, respectively. The gap prepulse inhibition of acoustic startle paradigm detected the tinnitus­like behavior of rats. The expression of TNF­α and NR2A genes were increased in the auditory cortex (AC) following long­term administration of salicylate, whereas the expression of IFN­Î³ genes decreased; however, the mRNA levels reversed back to normal baseline 14 days following the cease of salicylate administration. IL­6 gene expression, however, was not fundamentally altered by salicylate treatment. The data demonstrated that chronic salicylate administration induces tinnitus, in part, via dysregulation of cytokines and specific membrane receptors in the AC.

[Protective Effect of Lycium ruthenicum on Peripheral Blood System Against Radiation Injury in Mice].

OBJECTIVE: To study the protective effect of Lycium ruthenicum on peripheral blood system against radiation injury in mice. METHODS: Kunming mice were randomly divided into control group, model group, positive group and Lycium ruthenicum high dose (8 g/kg), middle dose (4 g/kg) and low dose (2 g/kg)treatment groups that experimented three days after irradiation. In the same way, groups were set at 7 days and 14 days after irradiation respectively. Lycium ruthenicum extract were administered orally to the mice in the three Lycium ruthenicum treatment groups and normal saline were administered orally to the mice in control group and model group for 14 days. Positive group were treated with radioprotective agent amifostine (WR-2721) at 30 min before irradiation. Except control group, mice in other groups received quantity of 5 Gy X-radiation whole body evenly with one time. Hemogram, organ index, DNA, Caspase-3, Caspase-6 and P53 contents were observed at the 3rd, 7th and 14th day after irradiation. RESULTS: Lycium ruthenicum significantly increased the total red blood cell count, hemoglobin count, the indexes of spleen and thymus and bone marrow DNA contents (P < 0.05), as well as decreased Caspase-3 and Caspase-6 contents in serum and the expression of P53 in intestinal crypt epithelial cells. CONCLUSION: The results showed that Lycium ruthenicum had protective effects on peripheral blood system against radiation injury in mice.

[Expression and significance of Twist1 and MMP-2 in endometrial endometrioid adenocarcinoma].

OBJECTIVE: To investigate the expression of Twist1 and MMP-2 protein and their significance in endometrial endometrioid adenocarcinoma. METHODS: The expression of Twist1 and MMP-2 protein in 70 cases of endometrial endometrioid adenocarcinoma was detected on tissue chips using immunohistochemical staining. RESULTS: The positive rates of Twist1 and MMP-2 protein expression were 65.7% and 67.1%, respectively. Both of the high expressions of Twist1 and MMP-2 were positively correlated with FIGO staging and tumor myometrial invasion (P < 0.05, respectively). Also the high expression of Twist1 was positively correlated with ovarian metastasis and the expression of MMP-2 was positively correlated with tumor grading (P < 0.05). The patients' overall survival and relapse-free survival in the group of high Twist1 expression were shorter than that in the group of low Twist1 expression (P < 0.05). The expression of MMP-2 was positively correlated with Twist1 expression (P < 0.01, respectively). CONCLUSIONS: The expression of Twist1 may be closely correlated with the tumor invasion, metastasis and prognosis in patients with endometrial endometrioid adenocarcinoma. The expression of Twist1 has a close relationship with MMP-2 in endometrial endometrioid adenocarcinoma.

Quantification of andrographolide sodium bisulphite in urine after intravenous injection to rats by LC-MS/MS.

A liquid chromatography-tandem mass spectrometry method for the determination of andrographolide sodium bisulphite (ASB) in rat urine was established and validated. To our knowledge, the analytical method is the first developed assay for the determination of ASB in urine samples. Dehydroandrographolide (DAG) was used as an internal standard. ASB and DAG were separated on a C(18) column and detected at negative ion mode using the mass transitions of m/z 413.2→287.2 and m/z 331.2→303.3, respectively. Good linearity was obtained over the range of 50-5000 ng/mL and the correlation coefficient was better than 0.99. The intra- and inter-day accuracy at all levels fell in the ranges of 85.8-101.4% and 87.9-97.5%, and the intra- and inter-day precision (RSD) were in the ranges of 4.3-11.2% and 8.4-13.3%, respectively. The recovery ranged from 96.1% to 98.3% and the matrix effects from 96.2% to 98.1%. Good stability was found under tested conditions. The method was successfully applied to a urinary excretion study of ASB in rats following intravenous administration of 80 mg/kg ASB.

[Investigation of birth state and disease spectrum in 1,434 hospitalized neonates].

OBJECTIVE: To investigate the birth state of neonates and the disease spectrum of hospitalized neonates from a primary hospital, and compare with the national data of the same period. METHODS: A retrospective investigation was carried out in 1,434 neonates born or hospitalized in this hospital from January 2005 to December 2005. RESULTS: During the investigation period, there were 1,100 neonates born in the department of obstetrics. The incidence of premature birth was 2.3%. The caesarean birth accounted for 54.2%, significantly higher than the national average (49.2%, p<0.01). The neonatal mortality was 0.2%. The incidences of antepartum hemorrhage, threatened abortion, and pregnancy infection in preterm infant' s mothers were significantly higher than those in full-term infant' s mothers. A total of 344 neonates were admitted to the department of pediatrics during the investigation period. Preterm infants accounted for 38.0% which was higher than the national average (26.2%; p<0.01). Beside preterm infants, asphyxia, respiratory distress syndrome (RDS), sepsis and intracranial hemorrhage were shown to have a significantly higher proportion than the national averages. The mortality of hospitalized neonates was 0.9%. CONCLUSIONS: The higher cesarean section rate should be controlled in our hospital. Prenatal health care and fetal monitoring should be strengthened to decrease the incidence of premature birth, RDS, sepsis and intracranial hemorrhage, thus reducing the mortality of neonates.

[Correlation of vascular endothelial growth factor D, microlymphatic density and microvessel density with development and metastasis of rectal cancer].

OBJECTIVE: To investigate the correlation of vascular endothelial growth factor D (VEGF-D) expression, microlymphatic density (MLD) and microvessel density (MVD) levels with the development and metastasis of rectal cancer. METHODS: Eighty specimens from resected middle-lower rectal cancer diagnosed by pathology were examined by immunohistochemistry for VEGF-D,MLD and MVD. Simultaneously, 40 biopsy specimens from rectal polyps and 80 specimens from normal rectal tissue were examined as controls. Correlation between the expression of above three factors and the tumor size, gross morphology, histological type, metastasis, differentiation grade, infiltration depth, Dukes stage, lymph node metastasis and long-distance metastasis before operation were investigated with Spearman method. RESULTS: (1) Positive expression rate of VEGF-D was 55 % (44/80) in rectal cancer, and zero in rectal polyps and normal rectal tissues. The expression of VEGF-D in rectal cancer was significantly higher than that in rectal polyps and normal rectal tissues(P<0.05). MLD was significantly higher in rectal cancer (2.80+/-1.31) than that in rectal polyps (0.50+/-0.72) and normal rectal tissues(0.25+/-0.44)(P<0.05).Meanwhile MVD was significantly higher in rectal cancer (80.10+/-23.18) than that in rectal polyps (27.00+/-11.01) and normal rectal tissues (10.45+/-5.34) (P<0.05). (2) VEGF-D, MLD and MVD were positively correlated with lymph node metastasis and long-distance metastasis before operation (P<0.05). (3) VEGF-D was positively correlated with MLD (P<0.05) and MLD was positively correlated with MVD as well(P<0.05). CONCLUSIONS: Lymphangiogenesis exists in rectal cancer tissues. VEGF-D and MLD can be used as good predictors of lymphangiogenesis and they are the important factors affecting biological behavior of rectal cancer. Lymphangiogenesis and angiogenesis may have a cooperative function in the development of rectal cancer.

[Study of quality on rhubarb from different habitats in Qinghai Province].

OBJECTIVE: To investigate the effect of different habitats on rhubarb quality. METHOD: The rhubarb samples from various parts of Qinghai province were analysed by fingerprint. RESULTS AND CONCLUSION: The distribution and quality of wild Tangute rhubarb is better than Palmate sorrel rhubarb. The quality of high altitude sampes are better than low altitudes. The quality which from the grassland of plateau is better than chestnut soil area's, and the wild is better than that of planting.

Antiviral therapeutic efficacy of foscarnet in hepatitis B virus infection.

Foscarnet (PFA), a viral DNA polymerase inhibitor, is a clinical agent for herpes viruses. The goal of the study was to evaluate the therapeutic efficacy of PFA in hepatitis B virus (HBV) infection. Intravenous infusion of PFA (1 g/day) for 4 weeks significantly reduced serum HBeAg (p<0.01) and HBV DNA copies (p<0.05) in 31 patients who were diagnosed with active chronic HBV infection (CHB) and had not received antiviral treatment previously. Alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and gamma glutamyl transpeptidase (gamma-GT) of the patients declined (p<0.001, 0.001 and 0.01, respectively). Kidney function (blood creatinine and urea nitrogen) remained unchanged. Another 21 lamivudine-resistant CHB patients with mutations at the tyrosine-methionine-aspartate-aspartate motif (YMDD) displayed a response to PFA similar to that mentioned above, with reductions in HBeAg (p<0.05), HBV DNA (p<0.01) and liver enzymes (ALT and AST, p<0.001; gamma-GT, p<0.05). Moreover, PFA reduced serum HBeAg (p<0.01), HBV DNA (P<0.05), AST (p<0.05) and ALT (p<0.02) in a cohort of 13 severe CHB patients with advanced liver damage. PFA was also evaluated in vitro and in vivo. PFA inhibited HBV DNA replication in HBV-transfected human HepG2 cells (2.2.15 cells) with reduced amount of HBV RC-DNA and DS-DNA. In the duck HBV-infected ducklings, PFA reduced viral DNA and duck HBsAg in the serum (p<0.01 for both).

Synthesis of 1-(3-phthalimido-2-oxobutyl)-4-substituted- phenylpiperazines and their anti-HIV reverse transcriptase activity.

AIM: Synthesis of 1-(3-phthalimido-2-oxobutyl)-4-substituted- phenylpiperazines (5-15). METHODS: The starting material nitrogen mustard hydrochloride (16), reacted with the corresponding substituted anilines to afford piperazine hydrochlorides (17-27), which were then coupled with 1-bromo-3-phthalimidobutan-2-one (4) to give the target compounds. RESULTS: Eleven target compounds (5-15) were synthesized, which were characterized by 1HNMR, IR and elemental analysis. CONCLUSION: Anti-HIV-1 RT using HIV reverse transcriptase P-66 protein test showed that compounds 11, 14, 10 and 13 possessed inhibitory effects against HIV-1 reverse transcriptase (RT), with IC50 29.80, 35.20, 43.77 and 63.76 mumol.L-1, respectively.