Research progress of small molecule modulators targeting Toll-like receptor 2 / 药学学报

Toll like receptors (TLRs) are the earliest discovered natural immune pattern recognition receptors (PRRs). The abnormality of TLR signal transduction pathway is the key factor leading to chronic inflammatory, cancer, nervous system disease and cardiovascular diseases. The development of TLR agonists and inhibitors has attracted much attention. Currently known TLR2 agonists, such as lipopeptides or their derivatives, have certain limitations in drug development due to their difficult synthesis, easy hydrolysis, and triggering inflammatory cytokine storms, while inhibitors have been rarely reported. New small molecule TLR2 agonists or inhibitors with higher stability are more likely to be developed as tumor immunotherapy or anti-inflammatory drugs.

Comparation of neurally adjusted ventilator assist and synchronized intermittent mandatory ventilation on respiratory function in premature infants with respiratory distress syndrome / 中国小儿急救医学

Objective To investigate the effect of neurally adjusted ventilator assist(NAVA) and synchronized intermittent mandatory ventilation(SIMV) on respiratory function in premature infants with respiratory distress syndrome.Methods A total of 54 preterm infants who were diagnosed neonatal respira-tory distress syndrome after birth and needed invasion mechanical ventilation in our hospital from Oct.2014 to Dec.2016 were given SIMV for 4 hours and NAVA mode ventilation for 4 hours,with a total of 4 cycles.The peak inspiratory pressure(PIP),tidal volume(TV),Compliance,respiratory rate(RR),Edi peak,Edi min, FiO2and mean airway pressure(MAP) were monitored every 30 minutes, and pressure of carbon dioxide (PaCO2)were monitored every 2 hours in different modes.Results The mean values of PIP[(19.5 ± 3.1) cmH2O,1 cmH2O=0.098 kPa],RR[(51.4 ± 7.9)breaths/min],Edi peak[(5.1 ± 3.2)μV],FiO2[(38.2 ± 12.9)%],MAP[(12.0 ± 0.8)cmH2O],PaCO2[(41.2 ± 9.3)mmHg,1 mmHg=0.133 kPa] and Edi min[(1.2 ± 1.4)μV] in NAVA mode were significantly lower than those in SIMV mode[(22.9 ± 3.4) cmH2O,(56.9 ± 8.3)breaths/min,(7.9 ± 4.9)μV,(39.9 ± 14.1)%,(13.2 ± 0.7)cmH2O,(47.1 ± 10.4)mmHg,(2.0 ± 1.7)μV,respectively](P<0.05).But the mean values of TV,Compliance in SIMV mode[(6.2 ± 1.0)ml/kg,(0.25 ± 0.33)ml/cmH2O,respectively] were significantly lower than those in the NAVA mode[(7.2 ± 0.9)ml/kg,(0.37 ± 0.21)ml/cmH2O,respectively](P<0.05).The downward trend of PIP,RR,Edi peak,FiO2,Edi min,MAP and upward trend of TV,Compliance were found during the first circle from NAVA mode to SIMV mode.The decrease and increase of above ventilator parameters were more obvious in NAVA mode compared with SIMV mode.Conclusion The respiratory muscle load is reduced, TV increases,and pulmonary compliance improves during NAVA ventilation.NAVA is better than SIMV in improving respiratory function of premature infants with respiratory distress syndrome. NAVA has lung protective effect.

Efficacy and complication of caffeine citrate and aminophylline in primary apnea of premature infants:a comparative analysis / 中国小儿急救医学

Objective To investigate the effects of caffeine citrate and aminophylline in treatment of primary apnea of premature infants and its related complications. Methods A total of 152 preterm infants who were diagnosed primary apnea within 10 days after birth were randomly divided into caffeine citrate group(n=77) and aminophylline group(n =75). The changes in the time of the apnea disappeared after treating,needing oxygen,non-invasive and invasive mechanical ventilation,and the incidence of bronchopul-monary dysplasia ( BPD ) , necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus (PDA),intercranial hemorrhage(ICH)were compared between the two groups. Results The time of the apnea disappeared after treating[(47. 4 ± 5. 3) h],needing oxygen[(20. 5 ± 7. 6) d],non-invasive mechani-cal ventilation[(8. 7 ± 4. 2) d] and invasive mechanical ventilation[(1. 0 ± 1. 3) d] in the caffeine citrate group were significantly lower than those in the aminophylline group [ ( 54. 8 ± 6. 2 ) h, ( 24. 4 ± 8. 5 ) d, (10.4±5.3)d,(10.4±5.3)d,respectively](P0. 05). Conclusion The caffeine citrate has a better efficacy in the treating primary apnea of preterm infants than aminophylline. It can also decrease the incidence of BPD,PDA and ICH in premature infants.

Rapid and Accurate Sequencing of Enterovirus Genomes Using MinION Nanopore Sequencer / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Knowledge of an enterovirus genome sequence is very important in epidemiological investigation to identify transmission patterns and ascertain the extent of an outbreak. The MinION sequencer is increasingly used to sequence various viral pathogens in many clinical situations because of its long reads, portability, real-time accessibility of sequenced data, and very low initial costs. However, information is lacking on MinION sequencing of enterovirus genomes.</p><p><b>METHODS</b>In this proof-of-concept study using Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) strains as examples, we established an amplicon-based whole genome sequencing method using MinION. We explored the accuracy, minimum sequencing time, discrimination and high-throughput sequencing ability of MinION, and compared its performance with Sanger sequencing.</p><p><b>RESULTS</b>Within the first minute (min) of sequencing, the accuracy of MinION was 98.5% for the single EV71 strain and 94.12%-97.33% for 10 genetically-related CA16 strains. In as little as 14 min, 99% identity was reached for the single EV71 strain, and in 17 min (on average), 99% identity was achieved for 10 CA16 strains in a single run.</p><p><b>CONCLUSION</b>MinION is suitable for whole genome sequencing of enteroviruses with sufficient accuracy and fine discrimination and has the potential as a fast, reliable and convenient method for routine use.</p>

Placental pathology and neonatal brain injury / 中国小儿急救医学

Placental pathologies include placental insufficiency,infection,meconium stained,abnormal planting and placental vascular anastomosis,et al.All those can lead to fetal and neonatal hypoxia ischemia or premature birth,which can cause brain damage.

Efficacy of different preparations of budesonide combined with pulmonary surfactant in the treatment of neonatal respiratory distress syndrome: a comparative analysis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the efficacy of different preparations of budesonide combined with pulmonary surfactant (PS) in improving blood gas levels and preventing bronchopulmonary dysplasia (BPD) in preterm infants with neonatal respiratory distress syndrome (NRDS).</p><p><b>METHODS</b>A total of 184 preterm infants who developed NRDS within 4 hours after birth were randomly administered with PS + continuous inhalation of budesonide aerosol (continuous aerosol group), PS+budesonide solution (solution group), PS + single inhalation of budesonide aerosol (single aerosol group), and PS alone, with 46 neonates in each group. The changes in arterial blood gas levels, rate of invasive mechanical ventilation after treatment, time of assisted ventilation, rate of repeated use of PS, and the incidence of BPD were compared between the four groups.</p><p><b>RESULTS</b>On the 2nd to 4th day after treatment, pH, PCO2, and oxygenation index (FiO2/PaO2) showed significant differences among the four groups, and the continuous aerosol group showed the most improvements of all indicators, followed by the solution group, single aerosol group, and PS alone group. The continuous aerosol group had a significantly shorter time of assisted ventilation than the other three groups (P<0.05). The solution group had a significantly shorter time of assisted ventilation than the single aerosol and PS alone groups (P<0.05). The rate of invasive mechanical ventilation after treatment, rate of repeated use of PS, and incidence of BPD showed significant differences among the four groups (P<0.05), and the continuous aerosol group had the lowest rates, followed by the solution group.</p><p><b>CONCLUSIONS</b>A combination of PS and continuous inhalation of budesonide aerosol has a better efficacy in the treatment of NRDS than a combination of PS and budesonide solution. The difference in reducing the incidence of BDP between the two administration methods awaits further investigation with a larger sample size.</p>

Medicinal vesiculation combined with quick cupping at Shenque (CV 8) for allergic rhinitis with syndrome of yang deficiency: a randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To compare the clinical efficacy differences between medicinal vesiculation combined with quick cupping at Shenque (CV 8) and regular medication for allergic rhinitis with syndrome of yang deficiency.</p><p><b>METHODS</b>Eighty-two cases were randomly divided into an observation group (42 cases) and a control group (40 cases). The observation group was treated with medicinal vesiculation combined with quick cupping at Shenque (CV 8). The medicinal vesiculation was applied at Feishu (BL 13), Gaohuang (BL 43), Fengmen (BL 12), Mingmen (GV 4) on the dog days in the summer, one treatment on the 1st dog-day, 2nd dog-day and last dog-day respectively with an interval of 10 days between two treatments. Three treatments were taken as one course, and totally one course was given. The quick cupping was applied at Shenque (CV 8), once a day, ten treatments were taken as one course, and totally three courses was given. The control group was treated with oral administration of loratadine and nasal spray of budesonide. The loratadine was given 10 mg per time, once a day for continuous 14 days; budesonide was given once a day, ten treatments were taken as one course, and totally three courses was given. The clinical efficacy in two groups after treatment was observed, and the contents of immune globulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5) and tumor necrosis factor-α (TNF-α) in peripheral serum were measured before and after the treatments.</p><p><b>RESULTS</b>Of all the 82 patients, 79 cases completed the treatment, and 1 patient in the observation group and 2 patients in the control group dropped out. The effective rate was 87.8% (36/41) in the observation group, which was superior to 78.9% (30/38) in the control group (P<0.05). After treatment, both groups effectively reduced the contents of IgE, IL-4, IL-5 and TNF-α, and the observation group had superior effect on reducing IgE and IL-4 to the control group (P<0.05).</p><p><b>CONCLUSION</b>The medicinal vesiculation combined with quick cupping at Shenque (CV 8) have better effect for allergic rhinitis with syndrome of yang deficiency than oral administration of loratadine and nasal spray of budesonide.</p>

Analysis of the initial efficacy of nedaplatin combined with megestrol in concurrent chemoradiotherapy for advanced cervical cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the early efficacy of nedaplatin combined with megestrol in concurrent chemoradiotherapy for advanced cervical cancer.</p><p><b>METHODS</b>Forty-two cases of cervical cancer (FIGO IIb to IVa) were divided randomly into two groups: radiotherapy alone (21 cases) and radiation plus chemotherapy (Nedaplatin) group. The same radiotherapy was given to the two groups. Patients of the RT + C group received nedaplatin 30 mg/m2 in intravenous drip infusion once weekly on day 1, for 4 to 5 weeks, and megestrol 160 mg orally every day during the radiation therapy.</p><p><b>RESULTS</b>The early outcome: the complete remission rate was 81.0% and partial remission rate was 19.0% in the RT + C group, significantly better than the CR (38.1%) and PR (42.9%) in the RT group. The 1-year survival rates in the two groups were 100% (21/21) and 81.0% (17/21), respectively, with a significant difference between the two groups (P<0.05).</p><p><b>CONCLUSIONS</b>The combination of nedaplatin and megestrol with concurrent chemoradiotherapy can improve the early outcome of advanced cervical cancer, with somewhat increased but tolerable adverse effects.</p>

Dose-effect relationship between androgen and neural protection in neonatal rats with hypoxic-ischemic brain damage and adverse effects of androgen / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore brain-protective effect of androgen, its dose-effect relationship and long-term adverse reaction.</p><p><b>METHOD</b>Seventy two 3-day-old SD rats were randomized into androgen group (n = 32), HIBD model group (n = 32) and sham operated group (n = 8). The androgen group and HIBD model group were further randomized into 30 mg/kg group, 60 mg/kg group, 120 mg/kg group and 240 mg/kg group, respectively. In androgen group and HIBD group, every rat was given testosterone or peanut oil, one time a day. Three days later, HIBD model was established by occlusion of the left common carotid artery and inhalation of 8% oxygen plus 92% nitrogen for 2.5 hours. Adult rats' ability of learning and memory was determined by water maze test. Escape latencies were recorded and analyzed by statistics. Vaginal cells of all female rats were examined everyday for identifying their estrous cycle. Female rats were allowed to live with normal adult male rats if the female rats were in estrous period. Vaginal cells were examined everyday until sperm was seen, which was the signal of gestation. Pregnancy rate and the number of embryos were recorded and analyzed by statistics. Acropetal coefficient was calculated. The testes and epididymis were taken from adult male rats, histopathological sections were made, and the structure of testis and epididymis were studied under light microscope.</p><p><b>RESULT</b>In Morris experiment, escape latencies (EL) of HIBD group were much longer than those of sham operation group (27.71 ± 3.19) s, time of first enter target (1(st) ET) was later than that of sham operation group (5.34 ± 0.83) s, times of target cross (TC) was less than that of sham operation group (18.88 ± 1.89) (P < 0.01, P = 0.0005). EL of androgen group (34.89 ± 3.68, 33.71 ± 3.38, 33.84 ± 3.45, 35.43 ± 2.43) were much shorter than that of HIBD group, 1(st) ET (5.39 ± 1.51, 6.28 ± 2.07, 5.09 ± 1.61, 5.85 ± 0.87) was earlier than that of HIBD group, TC (12.75 ± 2.05, 14.88 ± 3.36, 14.88 ± 2.36, 14.38 ± 1.60) was more than that of HIBD group (P < 0.01, P = 0.0001). Among the four doses groups of androgen group, EL, 1(st) ET and TC had no statistical significance (P > 0.05, P = 0.159). There were no statistical significance between male rats of androgen group [Testes acropetal coefficient (0.89 ± 0.07, 0.92 ± 0.08, 0.88 ± 0.11, 0.87 ± 0.09), epididymis acropetal coefficient (0.25 ± 0.02, 0.24 ± 0.05, 0.26 ± 0.04, 0.23 ± 0.05)], HIBD group and sham operation group (P > 0.05, P = 3.207). Among the four doses groups of androgen group had no statistical significance (P > 0.05, P = 6.663). There were no statistical significance between female rats of androgen group (pregnancy rate, 100%; times, 14.52 ± 3.34, 14.69 ± 2.28, 14.98 ± 2.67, 15.38 ± 3.07), HIBD group and sham operation group in pregnancy rate and times.</p><p><b>CONCLUSION</b>The intellectual ability of rats decreased after HI. Androgen could reduce the effect of HI on intellectual ability. Androgen had no adverse reaction to the reproductive capacity of adult rats.</p>

Influence of the of ultramicro-dosage heparin combining with low-molecule dextran on D-dimer in serum of infant patients with severe pneumonia / 中国医师进修杂志

Objeetive To observe the curative effect of ultramicro-dosage heparin (UMDH) combining with low-molecule dextran (LMD) on the D-dimer positive infant with severe pneumonia.Methods sixty-eight infant patienls.whose D-dimer in serum were positive,were randomly divided into two gmaps cutaneous injection for 4 times.Arier the D-dimer in serum became negative,the drug was stpped.In the heparin combining with LMD (HCLMD) group,the UMDH (same dosage as above) was used combining with the LMD.The dosage for LMD was 5 ml/kg once with general-speed intravenous drip and 1-2 times a day,which should be continued until the D-dimer in serum became negative.Results After 2-day's trestment,there was no obvious differences in the negative transfer rate of D-dimer between two groups(P＞0.05).However,after 3-4 day's treatment,the negative transfer rate in HCLMD group was absloutely higher than that in heparin group,there were obvious differences in two groups(P＜0.05).As for the death rate of illness,the death rate in HCLMD group was lower than that in hepari.group,being respectively 5.88% and 17.65%.Conclusion The use of UMDH combining with small-dosage LMD dextran can quickly improve the high condemation situation of blood and reverse the condition of infant patients with severe pneumonia.

Effects of androgen on phosphacan and NG2 proteoglycan expression and neurite regeneration in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of androgen on the expression of phosphacan and NG2 proteoglycan (NG2) and neurite regeneration in neonatal rats with hypoxic-ischemic brain damage (HIBD) and the potential mechanism underlying the protective effect of androgen against HIBD.</p><p><b>METHODS</b>One hundred and twenty neonatal Sprague-Dawley rats were randomly divided into three groups: sham-operated, HIBD and androgen treatment. HIBD was induced by the ligation of left common carotid artery and hypoxia exposure. The androgen treatment group rats were injected with testosterone propionate (25 mg/kg) immediately after HIBD. Phosphacan and NG2 expression in the cortex and the hippocampus was detected with the immunohistochemical method 24 and 72 hrs and 7 and 10 days after hypoxia-ischemia (HI). The ultrastructure and neurite regeneration of neurons in the cortex and the hippocampus were observed under a transmission electron microscope.</p><p><b>RESULTS</b>The neurite regeneration was obvious in the sham-operated group, but seldom in the HIBD group. The androgen treatment group showed increased neurite regeneration compared with the HIBD group. There were fewer phosphacan and NG2 positive cells in the cortex and the hippocampus in the sham-operated group. Phosphacan and NG2 expression in the cortex and the hippocampus was observed at 24 hrs, increased at 72 hrs, and peaked at 7 days after HI in the HIBD group and remained at a higher expression 10 days after HI than in the sham-operated group. The levels of phosphacan and NG2 expression in the cortex and the hippocampus in the androgen treatment group were significantly reduced compared with those in the HIBD group 24 and 72 hrs and 7 and 10 days after HI (P<0.01).</p><p><b>CONCLUSIONS</b>Phosphacan and NG2 may be important inhibitory factors for neurite regeneration following HIBD in neonatal rats. The neuroprotection of androgen against neonatal HIBD is produced possibly through an inhibition of phosphacan and NG2 expression.</p>

Effects of androgen on the expression of brain aromatase cytopigment and nerve growth factor in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of androgen on the expression of aromatase cytopigment P450 (AROM) and nerve growth factor (NGF) in the brain and brain ultrastructure in neonatal rats with hypoxic-ischemic brain damage (HIBD) in order to investigate the mechanism underlying the protective effect of androgen against HIBD.</p><p><b>METHODS</b>Ninety-six seven-day-old Sprague-Dawley rats were randomly divided into three groups: sham-operation, HIBD and androgen treatment (n=32 each). HIBD was induced by the ligation of left common carotid artery and hypoxia exposure. The rats in the androgen treatment and the HIBD groups were injected intraperitoneally with testosterone propionate (25 mg/kg) and arachis oil respectively immediately after hypoxia-ischemia (HI). After 24 and 72 hrs and 7 and 10 days of HI, AROM and NGF expression in the cortex and the hippocampus was detected with the immunohistochemical method. The ultrastructural changes of neurons in the cortex and the hippocampus were observed under a transmission electron microscope.</p><p><b>RESULTS</b>Nerve cells of the HIBD group showed obvious injuries including cell organ decreasing, cellularoedema, nuclear swelling, chromatic agglutination, mitochondria decreasing and swelling, as well as an increase in apoptotic cells. Compared with the HIBD group, the nerve cells in the androgen treatment group had integrated nuclear membrane, well-distributed chromatin and abundant cell organs, and less cell apoptosis and increased axon regeneration. There was a positive expression of NGF and AROM in the brain cortex and the hippocampus in the HIBD group 24 hrs after HI. The expression of NGF and AROM increased significantly 72 hrs after HI, peaked 7 days after HI and then began to decrease but remained at a higher level than that in the sham-operation group 10 days after HI. The NGF and AROM expression in the cortex and the hippocampus in the androgen treatment group was significantly higher than that in the sham-operation and the HIBD groups 72 hrs, and 7 and 10 days after HI.</p><p><b>CONCLUSIONS</b>Androgen treatment can promote axon regeneration and morphous recovery of neurons and decrease neural apoptosis in neonatal rats with HIBD. The neuroprotection of androgen is produced possibly through an increase in the expression of NGF and AROM in the brain.</p>

Protection of androgen against hypoxic-ischemic brain damage in neonatal rats and possible mechanisms / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Some research has shown that androgen has a neuroprotection against hypoxia-ischemia brain damage (HIBD). However, the relevant mechanism has not been fully elucidated. This study aimed to explore the neuroprotection of androgen against HIBD in neonatal rats and the possible mechanism.</p><p><b>METHODS</b>Sixty-four seven-day-old Sprague-Dawley (SD) rats were randomly assigned into three groups: Sham-operation, HIBD and Androgen. The HIBD model was induced by ligation of the left carotid common artery along with hypoxia exposure in neonatal rats from the latter two groups. The Sham-operation group was not subjected to hypoxia-ischemia (HI). The Androgen intervention group received an injection of testosterone propionate (25 mg/kg) immediately after HIBD. Bcl-2 and Bax protein expressions in the cortex and hippocampal CA region were detected by immunohistochemical method at 6, 24 and 72 hrs and at 7 days after HI. The contents of SOD and MDA in the brain tissue homogenate were measured by the thiobarbituric acid (TBA) method and the xanthine oxidase luminescence method respectively at 6, 24 and 48 hrs after HI.</p><p><b>RESULTS</b>There were few Bcl-2 and Bax immune positive cells in the cortex or hippocampus in the left hemisphere in the Sham-operation group at 6 hrs after operation. This was significantly different from the HIBD control and Androgen intervention groups (P < 0.01). The expression of Bcl-2 protein in the cortex and hippocampus of the Androgen intervention group was significantly higher than that of the HIBD control group at 6, 24 and 72 hrs after HI (P < 0.05 or 0.01). The expression of Bax protein in the cortex and hippocampus of the Androgen intervention group was significantly lower than that of the HIBD control group at 24 hrs after HI (P < 0.05). The SOD content in the brain tissue homogenate of the HIBD control group was significantly reduced, in contrast, the MDA content in the brain tissue homogenate of the HIBD control group increased significantly at 6 hrs after HI compared with the Sham-operation group (P < 0.05). The SOD content was reduced to a nadir and the MDA content increased to a peak at 24 hrs after HI in the HIBD control group. Androgen intervention increased significantly the SOD activity at 6,24 and 48 hrs after HI and decreased significantly the MDA content at 6 and 24 hrs after HI as compared with the HIBD control group (P < 0.05 or 0.01).</p><p><b>CONCLUSIONS</b>The neuroprotection of androgen against neonatal HIBD is produced possibly through an increase of Bcl-2 protein expression and a reduction in Bax protein expression, thus decreasing neuronal apoptosis after HI. There may also be a reduction in the consumption of antioxidant and an inhibition of the formation of oxidant free radicals to alleviate neuronal damage following HI.</p>

DNA content and its correlation with biological behavior of non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the relationship between DNA content and biological behavior and its prognostic significance in non-small cell lung cancer.</p><p><b>METHODS</b>Tumor DNA content was determined by flow cytometry in the specimens from 58 patients with resected non-small cell lung cancer. The DNA content of each cell subpopulation was expressed as the DNA index (DI), and an internal standard was provided by the normal pulmonary parenchymal cells in the same specimen. The prognostic value of DNA content in non-small cell lung cancer was assessed by Cox's model analysis.</p><p><b>RESULTS</b>In qualitative analysis, there was no relationship between DNA ploidy (diploidy or aneuploidy) and the following factors: tumor size, metastasis of lymph node, clinical stage, pathologic type, pathologic grade or survival. In quantitative analysis, high DNA index was observed in tumor size > 3 cm, metastasis of lymph node, stage III/IV, adenocarcinoma and shorter survival, which was statistically significant. Cox's model analysis showed that DNA index was a prognostic factor in non-small cell lung cancer and DNA index > 2.0 was an independent prognostic factor.</p><p><b>CONCLUSION</b>DNA index analysis is useful for the evaluation of the biological behavior and the prognosis of non-small cell lung cancer.</p>