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Background: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China., Methods: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG_012247.2 (NM_014251.3): c.852_855del, c.1638_1660dup, c.615+5G>A, and c.1751-5_1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests., Results: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ 2 =8.570, P=0.003) in general, with higher c.852_855del (54/6,818 vs. 13/5,492, χ 2 =17.328, P=0.000) but lower c.1751-5_1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638_1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly., Conclusions: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-21-58). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

The aim of this study was to evaluate the use of a novel porous silica carrier, AEROPERL ® 300 Pharma (AP), to improve the in vitro release and oral bioavailability of puerarin (PUE) in solid dispersions (SDs). PUE-AP SD formulations with different ratios of drug to silica (RDS) were prepared by the solvent method. The scanning electron microscopy (SEM) results indicated that the dispersion of PUE improved as the concentration of AP was increased. The differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results revealed that PUE mostly existed in an amorphous state in the SDs. The rate of drug dissolution from the SDs was significantly higher than that from the PUE powder (p < 0.05). The in vitro drug release percentage from the PUE-AP SDs increased as the RDS was reduced. The oral bioavailability of PUE from the SDs improved when using AP, as indicated by AUC (0-∞) , which was 2.05 and 2.01 times greater than that of the PUE (API) and PVP K30 SDs, respectively (p < 0.05). The drug content, in vitro release profiles, and the amorphous state of PUE in the PUE-AP SDs showed no significant changes after being stored at room temperature for 6 months or under accelerated conditions (40 ± 2°C, 75 ± 5% relative humidity) for 3 months. AP has a high pore volume, large specific surface area, excellent flowability, and hydrophilic properties, making it capable of improving the dissolution and bioavailability of poorly water-soluble drugs.

Objective: To investigate the preventive effects of thymosin-alpha1 against early ventilator-associated pneumonia (VAP) in the patients with mechanical ventilation., Methods: Fifty two patients with expectancy of mechanical ventilation over 48 h were divided into routine therapy group (n=26) and thymosin therapy group (n= 26) in random. The patients in routine therapy group were given intensive care unit (ICU) conventional treatment, and the patients in thymosin therapy group were given thymosin treatment additionally (1.6 mg subcutaneous injection, qd X 7 d). The incidence and occurrence time of VAP were observed, and the time of mechanical ventilation and ICU stay were recorded. The levels of CD3+, CD4+, CD4+ /CD8+ T lymphocyte, CD14+ mononuclear cell human leukocyte antigens-DR (CD14+ HLA-DR) and procalcitonin (PCT) were detected before mechanical ventilation and at the 3d and 7th d after mechanical ventilation., Results: The base line including the level of immunologic function had no difference between the two groups (P>0.05). The incidence of VAP in thymosin therapy group was lower than that in routine therapy group, but it was not significant difference (P>0.05). The durations of machine ventilation and ICU stay in thymosin therapy group were shorter than those in routine therapy group (P<0.05). The occurrence time of VAP in thymosin therapy group was significantly later than that in routine therapy group (P<0.05). At the 3rd and 7th d after mechanical ventilation, thymosin therapy group achived higher levels of CD3+, CD4+, CD4+ /CD8+ T lymphocyte and CD14+ HLA-DR than routine therapy group did (P<0.05)., Conclusion: Thymosinal may be able to improve immunologic function and prevent the incidence of early VAP in the patients with mechanical ventilation.

This study compared transdermal aconitine delivery using solid lipid nanoparticles (SLN) and microemulsion (ME) vehicles. Aconitine-loaded SLN and ME were formulated with the same surfactant, cosurfactant, and water content, with an equal amount of oil matrix (ATO 888 for SLN and ethyl oleate for ME). These nanosized formulations (70-90 nm) showed suitable pH values and satisfactory skin tissue biocompatibility. SLN contained a higher concentration of smaller nanoparticles, compared with that in ME. Neither of the nanocarriers penetrated across excised skin in their intact form. In vitro transdermal delivery studies found that transdermal aconitine flux was lower from SLN than from ME (p < 0.05), but skin aconitine deposition was higher using SLN (p < 0.05). Fluorescence-activated cell sorting indicated that in vitro uptake of fluorescently labeled SLN by human immortalized keratinocyte (HaCaT) cells was greater than that of ME, indicating that a transcellular pathway may contribute to cutaneous drug absorption more effectively from SLN. In vivo studies found that these formulations could loosen stratum corneum layers and increase skin surface crannies, which may also enhance transdermal aconitine delivery. SLN produced a more sustained aconitine release, indicating that compared with ME, this transdermal delivery vehicle may reduce the toxicity of this drug., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Objective: To discuss the tactics of mechanical ventilation in a human severe case of influenza A (H5N1) complicated with acute respiratory distress syndrome (ARDS)., Methods: The data of the patient infected by the influenza A (H5N1) admitted to People's Hospital of Guizhou Province on January 15, 2009, were analyzed and summarized., Results: The patient, a 29-year-old man, had been healthy in the past, but had exposed to the environment of bird flu before illness. The initial symptom was unremitting high fever, and then the clinical situation deteriorated progressively with occurrence of dyspnea. Pulmonary infiltrates were evident in the left lower lobe on January 19, and rapidly progressed to involve bilateral lungs presenting ARDS-like changes. Mechanical ventilation became the most important treatment among others. The ventilation mode was synchronized intermittent mandatory ventilation (SIMV)+ pressure support (PS) + positive end expiratory pressure (PEEP), following lung protective ventilatory strategies, with low tidal volume. The patient's condition improved day by day without developing multiple organ dysfunction. The patient fully recovered and was discharged on February 6., Conclusion: Early detection, early diagnosis, and finely effective intervention are to improve oxygenation by mechanical ventilation with low tidal volume and adequate PEEP are critical to reducing the mortality.