Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

Conjugated oligomers,as analogues of conjugated polymers,allow for constructing ultrafine fluorescent nanoparticles with improved sensing sensitivity due to their more precisely defined molecular structure and smaller size.Herein,a new porphyrin-pyridyl conjugated oligomer,i.e.,Zn-TPP-OMe,was designed and synthesized via Sonogashira coupling strategy and a super-small(～2.0 nm)water-soluble fluorescent nanoprobe(Zn-TPP-OMe nanoparticles(NPs))was subsequent obtained by nanoprecipitation method.Due to the addition reaction of chlorine atom to porphyrin ring,the fluorescence intensity of Zn-TPP-OMe NPs at 619-660 nm significantly decreased with increasing HCLO concentration.Meanwhile,Zn-TPP-OMe NPs aggregated obviously after adding HClO,achieving enhanced fluorescence quenching.The fluorescence detection mechanism was verified by transmission electron microscopy(TEM),proton nuclear magnetic resonance(1H NMR)and high resolution mass spectrometry(HRMS)analyses.The experimental results indicated that the porphyrin-pyridyl conjugated oligomer nanosystem had high sensitivity(LOD=0.005 μmol/L)and excellent selectivity in detection of HClO,and was successfully applied to the sensing of HClO in actual water samples.

Humans ; Multiple Myeloma/genetics* ; Neoplasm, Residual/diagnosis* ; Flow Cytometry ; High-Throughput Nucleotide Sequencing

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Antiviral Agents/adverse effects* ; Esophageal and Gastric Varices/complications* ; Liver Cirrhosis/complications* ; Treatment Outcome ; Gastrointestinal Hemorrhage/complications* ; Hepatitis B/drug therapy*

ObjectiveTo study the effect of flower removal on the content of three alkaloids in different parts of Fritillaria thunbergii from different regions and at different growth stages. MethodThe content of peiminine， peimine， and peimisine in the bulb， root， stem， and leaf of F. thunbergii after flower removal and with flower un-removed at different growth stages and in different regions were determined simultaneously by ultra-performance liquid chromatography-evaporative light scattering detection （UPLC-ELSD） method. The UPLC was conducted on ACQUITY UPLC BEH C₁₈ column （2.1 mm × 150 mm， 1.7 μm） with the mobile phase of 0.02% triethylamine aqueous solution （A） and methanol （B）elution gradient（0-2 min， 45%A； 2-5 min， 45%-25%A； 5-7 min， 25%A； 7-17 min， 25%-10%A； 17-20 min， 10%A）， flow velocity of 0.20 mL·min^-1， column temperature 35 °C， sample room temperature of 20 °C， and injection volume of 3 µL. The ELSD was carried out at drift tube temperature 45 °C and with the sprayer parameter of 40%. ResultThe flower removal significantly increased the yield of F. thunbergii. At the budding stage， the alkaloid content in the bulb of F. thunbergii from Ningbo in Zhejiang， Pan'an in Zhejiang， and Nantong in Jiangsu after flower removal were significantly higher than that of flowering un-removal treatment， while it showed no significant difference between the flower removal and un-removal treatments for the samples from Fengjie in Chongqing. At the flowering stage， the alkaloid content in the bulb of F. thunbergii from Nantong in Jiangsu after flower removal was significantly higher than that of flower un-removal treatment， while it showed an opposite trend for the samples from Pan'an in Zhejiang and Fengjie in Chongqing and had no significant difference between the two treatments for the samples from Ningbo in Zhejiang. At the bulb expansion stage， the alkaloid content in the bulb of F. thunbergii from Ningbo in Zhejiang and Pan’an in Zhejiang after flower removal were significantly higher than that of flower un-removal treatment， which was opposite for the samples from Nantong in Jiangsu and had no significant difference between the treatments for the samples from Fengjie in Chongqing. At the harvest stage， except for the samples from Pan'an in Zhejiang， the samples from the rest 3 regions showed decreased alkaloid content in the bulb after flower removal compared with that of flower un-removal treatment. The alkaloid content in the leaf was higher than that in the bulb of F. thunbergii at all growth stages and from different origins. ConclusionFlower removal can increase the yield of F. thunbergii. The alkaloid content in the bulb of F. thunbergii with flower removed was higher than that with flower un-removed at the budding stage， while this trend was reversed at the harvest stage. Both the yield and the alkaloid content of F. thunbergii from Pan'an in Zhejiang were increased by flower removal. The above-ground part of F. thunbergii has a potential development value.

Objective: To investigate the prevalence and risk factors of medication non-adherence in children with inflammatory bowel disease (IBD). Methods: A cross-sectional study was conducted in Children's Hospital, Zhejiang University School of Medicine from September 2020 to March 2022 and 112 children with IBD were enrolled. Their general information, medication adherence, and parental disease-related knowledge were collected by questionnaires. According to the medication adherence score, the children were divided into the adherence group (score of 6 to 8) and the non-adherence group (score of <6), then the demographic and clinical characteristics of the two groups were compared. Subsequently, a multivariate binary Logistic regression analysis was performed to determine the risk factors of medication non-adherence. Results: Of the 112 children, 76 were males and 36 females, with the age of 12.9 (9.5, 14.0) years. There were 50 (44.6%) in the non-adherence group and 62 (55.4%) in the adherence group. Regarding the demographic and clinical characteristics, the results showed that the dosage frequency and the parental disease related knowledge were associated with medication non-adherence (both P<0.05). Multivariate binary Logistic regression analysis showed that compared with 0-6 years old children, the risk of medication non-adherence was significantly increased in children aged 7-12 years (OR=9.30, 95%CI 1.58-54.87, P=0.014) and 13-18 years (OR=8.26, 95%CI 1.49-45.85, P=0.016); and the risk was also significantly increased in children who took medication twice or more per day (OR=12.88, 95%CI 2.77-59.80, P=0.001) compared with children who took medication once per day. Meanwhile, the parental score of the questionnaire on Crohn's disease and ulcerative colitis related knowledge (OR=0.76, 95%CI 0.66-0.89, P=0.001) was also a significant risk factor. Conclusions: Medication non-adherence is common in children with IBD. Children older than 7 years, a dosage frequency of twice or more per day, and parental poor disease-related knowledge are the independent risk factors for medication non-adherence in children with IBD. Clinicians should pay attention to promoting patients' adherence to improve clinical outcomes.
Male ; Female ; Child ; Humans ; Infant, Newborn ; Infant ; Child, Preschool ; Cross-Sectional Studies ; Prevalence ; Inflammatory Bowel Diseases/epidemiology* ; Medication Adherence ; Chronic Disease ; Risk Factors

Objective:To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS).Methods:This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration.Results:(1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant ( P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups ( P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant ( P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion:The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

With prominent medicinal value, Gelsemium elegans has been overexploited, resulting in the reduction of the wild resource. As a result, artificial cultivation turns out to be a solution. However, this medicinal species is intolerant to low temperature, and thus genes responding to the low temperature are important for the cultivation of this species. Based on the transcriptome database of G. elegans at 4 ℃, 29 differentially expressed GeERF genes were identified. Bioinformatics analysis of 21 GeERF gene sequences with intact open reading frames showed that 12 and 9 of the GeERF proteins respectively clustered in DREB subgroup and ERF subgroup. GeDREB1 A-1-GeERF6 B-1, with molecular weight of 23.78-50.96 kDa and length of 212-459 aa, were all predicted to be hydrophilic and in nucleus. Furthermore, the full-length cDNA sequence of GeERF2B-1 was cloned from the leaves of G. elegans. Subcellular localization suggested that GeERF2B-1 was located in the nucleus. According to the quantitative reverse-transcription PCR(qRT-PCR), GeERF2B-1 showed constitutive expression in roots, stems, and leaves of G. elegans, and the expression was the highest in roots. In terms of the response to 4 ℃ treatment, the expression of GeERF2B-1 was significantly higher than that in the control and peaked at 12 h, suggesting a positive response to low temperature. This study lays a scientific basis for the functional study of GeERF transcription factors and provides gene resources for the improvement of stress resistance of G. elegans.
DNA, Complementary ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism* ; Temperature ; Transcription Factors/metabolism*