ObjectiveThis study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg^-1） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg^-1·d^-1， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg^-1·d^-1， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110α （PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group， the model group showed significantly increased RVSP and RVHI （P<0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （P<0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP） >1， P<0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （P<0.01） and upregulated unsaturated fatty acid biosynthesis （P<0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）| >1.3， P<0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC| >1.3， P<0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （P<0.05）. ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Methods: Cervical radiographs were analyzed. EOP hyperplasia was classified into three subtypes with standardized length measurements. Variables encompassed demographics, ONL-related indices, and sagittal parameters. Subtype comparisons and multivariate regression analyses (with EOP length as dependent variable) were conducted. Results: Analysis of 187 CSM patients (64.2% male) identified gender-specific patterns: males exhibited greater EOP length (9.4±6.8 mm vs. 4.6±3.4 mm, p<0.001). Type III EOP demonstrated male predominance (82.4% vs. type I 31.8%, type II 51.4%; p<0.001), with associated longer hyperplasia length (11.6±6.6 mm vs. type II 5.1±1.9 mm, p<0.001). Type III EOP was associated with higher ONL prevalence (type III 64.8% vs. type I 45.5%, type II 41.9%; p=0.010) and longer ONL osteophyte length (type III 18.8±9.8 mm vs. type I 14.2±8.1 mm, type II 14.2±9.4 mm; p=0.046). Multivariate regression confirmed male sex (β=–3.82, p=0.009), ONL osteophyte length (β=0.16, p=0.017), T1 slope (β=0.27, p=0.041), and spino-cranial angle (β=–0.19, p=0.009) as factors independently associated with EOP length (adjusted R²=0.382). Conclusions Severe EOP hyperplasia exhibits a male-predominant distribution pattern and demonstrates significant radiological associations with ONL and cervical sagittal imbalance in CSM patients. These findings advocate for EOP evaluation in clinical evaluations to identify high-risk biomechanical profiles.

ObjectiveBy comparing the composition and content of volatile components in raw products， wine-washed products and wine-fried products of Ligusticum sinense cv. Chaxiong rhizome（LSCR）， to investigate the influence of wine processing on the volatile components of LSCR， in order to provide a basis for the development of quality standards for LSCR and its processed products. MethodsElectronic nose was used to identify the odors of LSCR， wine-washed and wine-fried LSCR， and their volatile components were detected by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the relative mass fractions of these components were determined by peak area normalization method. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on the obtained sample data by SIMCA 14.1 software， and the differential components of LSCR， wine-washed and wine-fried LSCR were screened according to the variable importance in the projection（VIP） value>1. Pearson correlation analysis was used to explore the relationship between volatile differential flavor components and electronic nose sensors. ResultsElectronic nose detection results showed that there were significant differences in the odors of LSCR， wine-washed and wine-fried LSCR， mainly reflected in the sensors S2， S4， S5， S6， S11， S12， S13. And a total of 62 compounds were identified from LSCR and its wine-processed products， among which 46， 50 and 51 compounds were identified from LSCR， wine-fried and wine-washed LSCR， respectively. There were 21 differential components between the raw products and wine-fried products， of which 10 components were increased and 11 were decreased after processing. There were 20 differential components between the raw products and wine-washed products， of which 11 constituents increased and 9 decreased after processing. There were 17 differential components between the wine-wash products and wine-fried products. Compared with the wine-washed products， the contents of 13 components in the wine-fried products increased， and the contents of 4 components decreased. The increasing trend of the content of phthalides in the wine-washed products was more obvious than that in the wine-fried products， but the content of total volatile components was higher in the wine-fried products than the wine-washed products. Correlation analysis showed that there were different degrees of correlation between the 7 differential sensors of electronic nose and 24 differential volatile components， mainly phthalides and olefins. ConclusionThe odor and the content of volatile components in LSCR changed obviously after wine processing， and n-butylphthalide， Z-butylidenephthalide and E-ligustilide can be used as the candidate differential markers of volatile components in LSCR before and after wine processing.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Objective:To evaluate the long-term effectiveness of lingual mucosal graft ureteroplasty (LMGU) for managing long-segment (≥5 cm) ureteral strictures in a multi-institutional cohort of patients.Methods:A multi-center retrospective case series study was conducted on clinical data from 42 patients undergoing LMGU for long-segment ureteral strictures (≥5 cm) across five institutions between February 2017 and June 2024. The cohort comprised 31 males and 11 females, with an age of (43.4±12.0) years (range: 15 to 64 years) and a body mass index of (24.6±2.6) kg/m2 (range: 16.0 to 30.0 kg/m2). Strictures involved the left ureter in 24 cases and right ureter in 18 cases, demonstrating a stricture length of (6.4±1.5) cm (range: 5.0 to 11.5 cm). Surgical interventions included either onlay ureteroplasty or augmented anastomotic ureteroplasty, selected according to intraoperative findings. Intraoperative parameters, postoperative complications, and follow-up outcomes were analyzed.Results:Laparoscopic surgery was performed in 22 cases and robot-assisted surgery in 20 cases. Among the 42 patients, 22 underwent onlay ureteroplasty while 20 received augmented anastomotic ureteroplasty. The graft length was (5.9±1.8) cm (range: 3.0 to 12.0 cm), operative time (191.5±55.6) minutes (range: 105.0 to 350.0 minutes), and intraoperative estimated blood loss (86.7±73.6) ml (range: 10.0 to 400.0 ml). All procedures were successfully completed without conversion to open surgery. The postoperative hospital stay was (7.6±2.0) days (range: 4.0 to 15.0 days), with double-J stent removal at 6 to 8 weeks postoperatively. During a follow-up of (49.1±25.0) months (range: 12.0 to 99.0 months), no stricture recurrence was observed in any patient.Conclusion:LMGU is a safe, feasible, and effective long-term technique for managing long-segment (≥5 cm) ureteral strictures.

Objective To analyze the pharmacological mechanism of Shenling Baizhu powder in the treatment of cancer cachexia based on the network pharmacological method and provide a reference for the clinical application of classical traditional Chinese medicine(TCM) prescriptions. Methods Through TCMSP and BATMAN-TCM databases, the main chemical components and their targets of the TCM prescription of Shenling Baizhu powder were obtained, and the active components of the TCM were screened according to ADME. The main targets of cancer cachexia were obtained through OMIM, Genecards, Disgenet and DRUGBANK databases, and protein interaction analysis was conducted using String platform to build a PPI network. The “drug-active ingredient-target” network of Shenling Baizhu powder was constructed by Cytoscape 3.7.2 software, and then the biological processes and pathways involved were analyzed by using Metascape platform. Finally, molecular docking verification was conducted by Discovery Studio. Results The core active ingredients of Shenling Baizhu powder in the treatment of cancer cachexia were quercetin, kaempferol, pyrolignous acid, stigmasterol, luteolin, β-sitosterol, etc. The core targets were AKT1, TP53, TNF, IL-6, MAPK3, CASP3, JUN, CTNNB1, HIF1A, EGFR, etc. The molecular docking test also showed that the top 10 active ingredients, such as pyrolignous acid, stigmasterol and β-sitosterol, had good binding activities with most of the target sites. The biological pathway of Shenling Baizhu powder in treating cancer cachexia wss mainly to regulate tumor related pathway, metabolism related pathway, inflammatory factors and appetite related pathway. Conclusion This study preliminarily revealed the mechanism of action of Shenling Baizhu powder in treating cancer cachexia with multi components, multi targets and multi pathways, which provided a basis for the clinical development and utilization of Shenling Baizhu powder.

OBJECTIVE: To observe the clinical efficacy of Fu's subcutaneous needling based on "multi-joint muscle spiral balance chain" theory for cervical vertigo (CV) and its effect on blood flow velocity of vertebral artery. METHODS: A total of 60 patients with CV were randomized into a Fu's subcutaneous needling group and a medication group, 30 cases in each one. In the Fu's subcutaneous needling group, Fu's subcutaneous needling was delivered at Dazhui (GV14), the flexible tube was retained for 5 min after sweeping manipulation, and the treatment was given once every other day, 3 times a week for 3 weeks. In the medication group, betahistine mesylate tablet and diclofenac sodium dual-release enteric capsule were taken orally for continuous 3 weeks. Before treatment, after treatment, and in follow-up of one month after treatment completion, the scores of dizziness handicap inventory (DHI) and visual analogue scale (VAS) were observed; before and after treatment, the blood flow velocity of vertebral artery was measured by transcranial Doppler, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment and in follow-up, each item scores and total scores of DHI were decreased compared with those before treatment in the two groups (P<0.05); the VAS scores after treatment in the two groups, as well as the VAS score in follow-up of the Fu's subcutaneous needling group, were decreased compared with those before treatment (P<0.05). In the Fu's subcutaneous needling group, after treatment and in follow-up, the physical scores and the total scores of DHI, and the VAS scores were lower than those in the medication group (P<0.05); in follow-up, the emotional and functional scores of DHI were lower than those in the medication group (P<0.05). After treatment, the mean blood flow velocity (Vm) of the left vertebral artery (LVA) and the right vertebral artery (RVA) was increased compared with that before treatment in the two groups (P<0.05), and the Vm of LVA and RVA in the Fu's subcutaneous needling group was higher than that in the medication group (P<0.05). The total effective rate was 100.0% (30/30) in the Fu's subcutaneous needling group, which was superior to 73.3% (22/30) in the medication group (P<0.05). CONCLUSION Fu's subcutaneous needling based on the "multi-joint muscle spiral balance chain" theory can effectively alleviate the vertigo and neck pain, and improve the blood flow velocity of vertebral artery in CV patients, and has a long-term therapeutic effect.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/instrumentation* ; Vertebral Artery/physiopathology* ; Adult ; Vertigo/physiopathology* ; Aged ; Blood Flow Velocity ; Treatment Outcome ; Acupuncture Points ; Young Adult