Objective To explore the etiology and pathogenesis of Hirschsprung disease(HD) and the role of nitric oxide in pathophysiology of HD. Methods The whole amount preparations of dilative and transitional segments were stained by NADPH\|diaphorase histochemistry mothod,and colonic walls were digested by dispase. Then the NOS positive nervous structure were observed by light and scanning electron microscope. Results In dilative segment, under light microscope, ganglion and neuron were bigger and more darkly stained. Intraganglionic neurons distributed mostly in peripheral area of ganglion and basal part of ganglionic fiber bundles. Under scanning electron microscope, the neurons were denser, more nerve fibers from them and connected with each other in all dimensions. And more transverse connected fibers between neurons which were arranged along muscle fibers. Myenteric plexus even connected with the submucosal plexus by nerve fibers which passed through circular muscle layer. In transitional segment, under light microscope, intraganglionic neurons cytoplasm were lightly stained and also variedly. The ganglion and neurons of the segment were smaller, and the fibers from them were thinner and paler than those of the dilative segment. Under scanning electron microscope, neurons' density was lower, the fiber connection between neurons and muscle fibers/neurons was lesser. In the transitional segment, neurons and nerve fibers were distributed linearly along the longitudinal muscle fibers. Conclusion Our results indicated that an intimate relationship existed between the development of Hirschsprung disease and abnormal distribution and metabolism of NOS positive neuron in colonic wall. [

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

This study was carried out to investigate the pharmacokinetics/bioequivalence of levornidazole disodium phosphate by using stable isotope labeled drug, evaluated the pharmacokinetic profile and confirmed the prodrug characteristics of levornidazole disodium phosphate in monkey. Levornidazole (Drug A) and stable isotope ¹⁵N labeled levornidazole disodium phosphate (Drug B) were mixed with equal mole amount (experiment I); stable isotope ¹⁵N labeled levornidazole disodium phosphate (Drug B) and levornidazole disodium phosphate (Drug C) were mixed with equal mole amount, respectively. After giving the mixed drugs to the monkey, the concentration of ¹⁵N-levornidazole disodium phosphate, levornidazole disodium phosphate, ¹⁵N-levornidazole and levornidazole in plasma samples of pre-dosing and 24 h after administration were analyzed by a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Pharmacokinetic calculations were performed through non-compartmental analysis using WinNonlin software. Two-sided 90% confidence intervals (CI) were used to evaluate the bioequivalence of two drugs. The results showed that levornidazole disodium phosphate was metabolized to levornidazole rapidly after administration, the body exposure were increased with the dosage. The method of bioequivalence used in this study was different from the traditional two periods, crossover design. By using the method of this study, the effects of administration period, intra-individual variability, and sequence of administration on bioequivalence were avoided. The results of this study had successfully supported the pharmacokinetic and bioequivalence study of this drug in human using the same approach.