ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

Objective To explore the method for establishing a pig left lung orthotopic transplantation model. Methods A total of 4 male Yorkshire pigs weighing (40.0±2.5) kg underwent surgical procedures, including anesthesia, tracheal intubation, donor lung procurement, and recipient lung transplantation. Histological morphology and blood gas analysis of the transplanted lungs were assessed 2 hours after reperfusion to evaluate the histological changes and function of the transplanted lungs. Results The pigs underwent left lung in situ transplantation, effectively simulating conditions relevant to human lung transplantation. Two hours after the transplantation, arterial blood gas analysis showed that arterial partial pressure of oxygen was 155.4-178.6 mm Hg, arterial partial pressure of carbon dioxide was 53.1-62.4 mm Hg, and the oxygenation index was 310.8-357.2 mm Hg. Hematoxylin and eosin staining indicated a low degree of pulmonary edema and minimal cellular infiltration. Conclusion The pig left lung orthotopic transplantation model possesses strong operability and stability. Researchers can replicate this model according to the described methods and further conduct basic research and explore clinical translational applications.

Objective:To explore the trend of hearing changes in infants with GJB2 gene p.V37I mutation at different months. Methods:The subjects were 54 children（108 ears） with p.V37I homozygous or compound heterozygous mutation in GJB2 gene. All the subjects underwent auditory brainstem response, auditory steady-state response, acoustic immittance and other audiological tests. Children were divided into three groups according to their age, 26 cases in group A were ≤3 months old, 17 cases in group B were>3~≤6 months old, and 11 cases in group C were>6 months old. Statistical analysis was performed on the three groups of ABR response threshold, hearing degree, the ASSR average response threshold of four frequencies and the ASSR response thresholds for each frequency of 500, 1 000, 2 000 and 4 000 Hz. Results:Among the 54 cases, 35 were male and 19 were female, with an age rang of 2-27 months and a median age of 4 months. The ABR response threshold of the three groups were ranked from low to high as group A, group B and group C, and the difference was statistically significant（P<0.05）. The ABR response thresholds of the three groups were ranked from low to high as group A, group B, and group C. The comparison between groups showed that the ABR response thresholds of group C was higher than that of group A（P=0.006）. The proportion of confirmed hearing loss in the three groups was 34.61%, 50.00% and 63.64%, respectively, and the difference of hearing level among the three groups was statistically significant（P<0.05）. The comparison between groups showed that the difference between group A and group C was statistically significant（P=0.012）, normal hearing accounted for the highest proportion in group A（65.39%）, while mild hearing loss accounted for the highest proportion in group C（45.46%）. The ASSR average response thresholds of the four frequencies in the three groups were ranked from low to high as group A, group B and group C, and the difference is statistically significant（P<0.05）. The comparison between groups showed that response ASSR thresholds of group C was higher than that of group A（P=0.002）. Response thresholds of ASSR in each frequency in the three groups were all ranked from low to high as in group A, group B and group C, and the differences were statistically significant（P<0.05）. Compared with each other between groups, response ASSR thresholds of group C was higher than those of group A（P=0.003） and group B（P=0.015） at 500 Hz, while response ASSR thresholds of group C was higher than group A at 1 000 Hz（P=0.010） and 2 000 Hz（P<0.001）, and there was no statistical difference at 4 000 Hz. Conclusion:The incidence of hearing loss in GJB2 gene p.V37I mutation increased with age, and the degree of hearing loss increased, the hearing progression was mainly 500, 1 000 and 2 000 Hz suggesting regular follow-up and alert to hearing changes.
Humans ; Connexin 26 ; Male ; Female ; Infant ; Child, Preschool ; Mutation ; Evoked Potentials, Auditory, Brain Stem ; Connexins/genetics* ; Auditory Threshold ; Hearing/genetics* ; Hearing Loss/genetics*

Objective:To explore the hearing changes of children with different genotypes of SLC26A4 with enlarged vestibular aqueduct（EVA） using the linear mixed effect model（LMM）, providing evidence for the risk prediction of progressive hearing loss. Methods:A total of 48 children with EVA diagnosed in our hospital from January 2017 to January 2024. All subjects underwent two or more auditory tests. According to the results of deafness gene screening and sequencing, the genotypes are divided into: type A: homozygous mutation of c. 919-2A>G, type B: compound heterozygous or heterozygous mutation containing c. 919-2A>G, and type C: no mutation site of c. 919-2A>G of SLC26A4 gene. LMM was used to analyze the hearing thresholds change of 500 Hz, 1 000 Hz, 2 000 Hz, 4 000 Hz and the average in children with different genotypes with age. Results:A total of 92 ears, 314 audiograms of 48 children were included, the median number of audiograms was 3, the median age of initial diagnosis was 4 months, and the median follow-up time was 13 months. According to LMM, the standard deviation of random effects between patients and ears was large. There was no significant difference in hearing thresholds of different frequencies and the average in genotype A, genotype B, and genotype C, indicating that genotype had no effect on hearing threshold. There is an interaction between age and genotype. Taking genotype C as the reference, children with genotype B had the lowest increase in 500 Hz, 1000 Hz, and the average hearing threshold, followed by type A. Conclusion:EVA children exhibit substantial inter-individual/ear hearing threshold variability. Low-frequency thresholds progress slower than high frequencies. Genotype modulates progression rates, with wild-type（Type C） demonstrating fastest deterioration, supporting personalized auditory monitoring strategies.
Humans ; Vestibular Aqueduct/abnormalities* ; Genotype ; Sulfate Transporters ; Mutation ; Auditory Threshold ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Child, Preschool ; Hearing Loss/genetics* ; Hearing Tests ; Linear Models ; Infant

ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region （3’UTR） of slit guidance ligand 1 （Slit1） （Slit1-3’UTR） on the fibrotic phenotypes of cardiac fibroblasts （CFs） and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs （mCFs）. The expression of fibrosis-related genes in mCFs， such as collagen type 1 alpha1（COL1A1）， collagen type 3 alpha3 （COL3A1） and alpha smooth muscle actin （α-SMA） were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ （Ang Ⅱ） was used to treat mCFs， and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt， miR-34a-5p mimic was transfected into mCFs， followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt， and the levels of miR-34a-5p and its target gene SIRT1（si-SIRT1） in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes， proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs， while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes， and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.

Objective To investigate the clinical effects of different right lung volume reduction techniques when the donor lung is oversized and mismatched with the recipient. Methods Clinical data of 10 recipients who underwent right lung volume reduction lung transplantation at the First Affiliated Hospital of Xi'an Jiaotong University from October 2022 to June 2024 were collected, including gender, age, primary disease type, and type of transplantation. A retrospective analysis was performed on postoperative complications within 90 days, duration of mechanical ventilation, hospital stay, and survival status to explore the impact of different volume reduction techniques on the survival rate of lung transplant recipients. Results A total of 10 right lung volume reduction recipients were included in this study, with 2 cases of upper lobe reduction, 7 cases of middle lobe reduction, and 1 case of lower lobe reduction. Three recipients developed airway complications (one each with upper, middle, and lower lobe reduction). The 30-day survival rate was 90% and the 1-year survival rate was 70%. One recipient with upper lobe reduction died of septic shock during the perioperative period, one with lower lobe reduction died of airway anastomotic fistula 2 months after surgery, and one with middle lobe reduction died of renal insufficiency 1 year after surgery. All 7 recipients with middle lobe reduction successfully passed the perioperative period, with one case of airway anastomotic stenosis (1/7). The average duration of mechanical ventilation was 71 hours, and the average hospital stay was 26 days. The 30-day survival rate was 7/7, and the 1-year survival rate was 6/7. Conclusions Middle lobe reduction in right lung transplantation surgery has the advantages of low incidence of airway complications, good safety, and minimal loss of lung function, and may be a better right lung volume reduction option with potential for application.

Objective To construct and evaluate the prediction model of maternal mortality in Yunnan Province,and predict the maternal mortality rate in Yunnan Province from 2024 to 2030.Methods Based on the maternal mortality rates in Yunnan Province from 1994 to 2023,a grey prediction model and a autoregressive integrated moving average model were constructed,The models were compared using mean absolute error,mean square error and root mean square error to assess their fitting performance,and the optimal model was used to predict the maternal mortality rate in Yunnan Province from 2024 to 2030.Resuls The maternal mortality rate in Yunnan Province showed a continuous decline from 1994 to 2023(χ2=50 170.0,P<0.05).The mean absolute error,mean-square error and root mean-square error for the grey prediction model were 2.424,12.389,3.519,respectively,while for the differential autoregressive moving average model,they were 3.966,27.651,5.258,respectively.The prediction effect of the grey prediction model is superior to that of the autoregressive integrated moving average model,with a posterior difference ratio C=0.079 and a low probability error P=1,indicating a prediction accuracy of level 1.Using the grey prediction model,the maternal mortality rates for Yunnan Province from 2024 to 2030 are 10.05/100 000,9.16/100 000,8.34/100 000,7.59/100 000,691/100 000,6.30/100 000 and 5.73/100 000,respectively.Conclusion The grey prediction model has a good prediction effect on maternal mortality in Yunnan Province.It is predicted that the maternal mortality rate in Yunnan Province in 2030 can meet the control targets outlined in the"Healthy China 2030 Plan",the"Outline of Chinese Women's Development(2021-2030)"and the"Yunnan Women's Development Plan(2021-2030)".

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal