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

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.

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*

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*

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.
Amyloidosis/diagnosis* ; Humans ; Immunoglobulin Light Chains ; Immunoglobulin Light-chain Amyloidosis/therapy* ; Multiple Myeloma/therapy* ; Prognosis ; Retrospective Studies

Objective: To analyze mortality and its trend of chronic respiratory diseases (CRD) in China from 1990 to 2019. Methods: Based on the provincial results of China from the 2019 Global Burden of Disease (GBD) study, the average annual percent change (AAPC) of standardized mortality rates of different CRDs were analyzed by using Joinpoint 4.8.0.1, and the age-standardized mortality rate of CRD was calculated by using the GBD 2019 world standard population. Based on the comparative risk assessment theory of GBD, the attributable deaths due to 12 CRD risk factors were estimated, including smoking, indoor air pollution, occupational gas exposure, particulates and smog exposure, environmental particulate pollution, low temperature, passive smoking, ozone pollution, occupational exposure to silica, occupational asthma, high body mass index, high temperature and occupational exposure to asbestos. Results: From 1990 to 2019, the number of deaths and standardized mortality of chronic obstructive pulmonary disease (COPD) showed a downward trend (P<0.001). The number of COPD deaths decreased from 1 244 000 (912 000 - 1 395 000) in 1990 to 1 037 000 (889 000 - 1 266 000) in 2019. AAPC=-0.9% (95%CI: -1.5% - -0.3%), P<0.001; The standardized mortality rate decreased from 217.9/100 000 (163.3/100 000 - 242.0/100 000) in 1990 to 65.2/100 000 (55.5/100 000 - 80.1/100 000) in 2019. AAPC= -4.2% (95%CI:-5.2% - -3.2%), P<0.001. The number of deaths from asthma decreased from 40 000 (30 000 - 58 000) in 1990 to 25 000 (20 000 - 31 000) in 2019. AAPC=-2.0% (95%CI: -2.6% - -1.4%), P<0.001; The standardized mortality rate of asthma decreased from 6.4/100 000 (4.7/100 000 - 9.5/100 000) in 1990 to 1.5/100 000 (1.2/100 000 - 1.9/100 000) in 2019. AAPC=-5.1% (95%CI: -5.8% - -4.4%), P<0.001. The number of pneumoconiosis deaths decreased from 11 000 (8 000 - 14 000) in 1990 to 10 000 (8 000 - 14 000) in 2019, AAPC=-0.2%(95%CI:-0.4% - 0.1%), P=0.200; The standardized mortality rate of pneumoconiosis decreased from 1.4/100 000 (1.0/100 000 - 1.7/100 000) in 1990 to 0.5/100 000 (0.4/100 000 - 0.7/100 000) in 2019. AAPC=-3.1% (95%CI: -3.4% - -2.8%), P<0.001. The number of deaths from pulmonary interstitial diseases and pulmonary sarcoidosis increased from 3 000 (3 000 - 6 000) in 1990 to 8 000 (6 000 - 10 000) in 2019, AAPC=3.5% (95%CI: 2.7% - 4.2%), P<0.001; The corresponding standardized mortality rate changed little from 1990 to 2019, and AAPC was not statistically significant.The age-standardized mortality rates of different CRDs were higher in men than those in women. In 1990 and 2019, the mortality rates of COPD, asthma, pneumoconiosis and interstitial pulmonary disease and pulmonary sarcoidosis increased with age. In 2019, the population attributable fractions (PAFs) for smoking, environmental particulate pollution, occupational gas exposure, particulate and smog exposure, low temperature exposure and passive smoking were 71.1% (68.0% - 74.3%), 24.7% (20.1% - 30.0%), 19.3% (13.0% - 25.4%), 15.7% (13.6% - 18.3%) and 8.8% (4.5% - 13.1%) respectively in men, and the PAFs for environmental particulate pollution, smoking, low temperature exposure, occupational gas exposure, particulate and smog exposure, and passive smoking were 24.1% (19.6% - 29.3%), 21.9% (18.7% - 25.2%), 16.4% (14.0% - 19.2%), 15.6% (10.2% - 21.1%) and 14.7% (7.9% - 21.3%) respectively in women. Conclusions: During 1990-2019, the overall death level of CRD decreased significantly in China, but it is still at high level in the world. Active prevention and control measures should be taken to reduce the death level caused by CRD.
Asthma ; China/epidemiology* ; Female ; Global Burden of Disease ; Humans ; Male ; Mortality ; Pulmonary Disease, Chronic Obstructive ; Quality-Adjusted Life Years

Obvious epigenetic differentiation occurred on Lycium barbarum in different cultivation areas in China. To investigate the difference and change rule of DNA methylation level and pattern of L. barbarum from different cultivation areas in China, the present study employed fluorescence-assisted methylation-sensitive amplified polymorphism(MSAP) to analyze the methylation level and polymorphism of 53 genomic DNA samples from Yinchuan Plain in Ningxia, Bayannur city in Inner Mongolia, Jingyuan county and Yumen city in Gansu, Delingha city in Qinghai, and Jinghe county in Xinjiang. The MSAP technical system suitable for the methylation analysis of L. barbarum genomic DNA was established and ten pairs of selective primers were selected. Among amplified 5'-CCGG-3' methylated sites, there were 35.85% full-methylated sites and 39.88% hemi-methylated sites, showing a high degree of epigenetic differentiation. Stoichiometric analysis showed that the ecological environment was the main factor affecting the epigenetic characteristics of L. barbarum, followed by cultivated varieties. Precipitation, air temperature, and soil pH were the main ecological factors affecting DNA methylation in different areas. This study provided a theoretical basis for the analysis of the epigenetic mechanism of L. barbarum to adapt to the diffe-rent ecological environments and research ideas for the introduction, cultivation, and germplasm traceability of L. barbarum.
China ; DNA Methylation ; DNA Primers ; Epigenesis, Genetic ; Lycium/genetics*