ObjectiveTo analyze the characteristics of 150 patients with spinal cord injury complicated with spasticity. MethodsA cross-sectional survey was conducted on 150 patients with spinal cord injury accompanied by spasticity from September, 2019 to December, 2024. Their age, gender, cause of injury, injury site, severity of injury, spasticity severity and other indicators were recorded. The relationships between different characteristics were analyzed, and a correlation analysis of disease duration, spasticity grade, injury level, injury severity and age were conducted. ResultsThere was no significant difference in age distribution between patients with tetraplegia and paraplegia (Z = 0.806, P = 0.420). The proportions of trauma (χ² = 3.982, P = 0.046) and tetraplegia (χ² = 10.559, P = 0.010) were higher in males than in females. Trauma was the main cause of injury in both tetraplegia and paraplegia patients; the proportion of tetraplegia was higher than paraplegia in trauma patients, while paraplegia was higher than tetraplegia in non-trauma patients (χ² = 11.885, P < 0.001). Patients with tetraplegia was dominated by incomplete injury, whereas patients with paraplegia was dominated by complete injury (χ² = 10.885, P = 0.012). Grade A injury was predominant in trauma patients (P = 0.003). Spasticity grade showed a very weak positive correlation with disease duration (r = 0.175, P = 0.032) and age (r = 0.168, P = 0.040). Injury severity showed a very weak positive correlation with age (r = 0.183, P = 0.025). ConclusionCharacteristics of patients with spinal cord injury complicated with spasticity is different with gender, cause of injury, injury level, injury severity.

O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer Escherichia coli HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing aspB, aspA, and thrA^C1034T) were enhanced to obtain an initial strain accumulating 13.37 g/L OAH. Subsequently, the co-factor synthesis genes were integrated to supply reducing power and energy, which increased the yield to 15.79 g/L. The OAH yield of the engineered strain OAH28 was further increased to 17.49 g/L by strengthening the acetic acid reuse pathway, improving the supply of acetyl-CoA, and regulating the expression of MetX from different sources. Finally, in a 5 L fermenter, OAH28 achieved an OAH titer of 47.12 g/L, with a glucose conversion rate of 32% and productivity of 0.59 g/(L·h). The results lay a foundation for increasing the OAH production by metabolic engineering and give insights into the industrial production of OAH.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Homoserine/biosynthesis* ; Fermentation

Synthetic biology is a crucial tool for the development of the bio-industry and bio-economy, representing a significant aspect of new quality productive forces. As a core course for graduate students in bioengineering, Synthetic Biology plays a vital role in ensuring the supply of essential talents for the development of the bio-industry in the new era. To better serve regional economic development and provide high-level talents for China's progress in the bio-industry, we analyzed typical issues encountered in the past teaching activities, set up a multi-disciplinary teaching team, optimized the course contents, adjusted the teaching mode, and mobilized students' learning interest. With the application of scientific research project as the starting point, we guided students to think and discuss deeply through the simulation of application writing and project defense, which improved students' critical thinking and innovative thinking. With industrialization as a focus, we explored a new training model combining production, education, and research through the joint practice base of the university and enterprises introduced typical cases of biomanufacturing to encourage students to engage in scientific research. The teaching reform significantly enhances the comprehensive abilities and national sentiments of graduate students. This paper hopes to serve as a reference for colleagues engaged in teaching in this field.
Synthetic Biology/education* ; Teaching ; China ; Humans

Objective:To analyze the clinical characteristics of tigecycline-related adverse reactions and provide the basis for the safe and rational use of the drug.Methods:Adverse reaction reports with suspected drug as tigecycline from Beijing Adverse Drug Reaction Monitoring Center from January 1st, 2019 to June 30th, 2024 were collected. The adverse reaction reports were standardized using the preferred term (PT) and system organ class (SOC) in the Chinese updated edition (2015 version) of the World Health Organization Adverse Reaction Terminology. The patients' general condition, tigecycline use, and adverse reaction occurrence (including latency, severity, treatment, outcome, and correlation evaluation) were descriptively and statistically analyzed. Results:A total of 408 tigecycline-related adverse reaction reports were entered, including 153 females (37.5%) and 255 males (62.5%). The age was (68±21) years, ranging from 2 to 99. The main reasons for tigecycline use were infections of lung, blood flow, skin and skin soft tissue, etc. The pathogens were mainly Klebsiella pneumoniae, Acinetobacter baumanii, Escherichia coli, etc. The usage and dosage of tigecycline in most patients were in line with the instructions. Four hundred and eight adverse event reports involved 11 SOCs and 580 PTs. The top 3 SOCs were gastrointestinal diseases (195 case times, 33.62%), vascular, bleeding and coagulation diseases (183 case times, 31.55%), and hepatobiliary diseases (142 case times, 24.48%). The main clinical manifestations were nausea, vomiting, diarrhea, etc. The main laboratory abnormalities were decreased plasma fibrinogen, decreased platelet count, increased alanine aminotransferase, increased aspartate aminotransferase, and increased bilirubin. There were 27 case times of adverse reactions that were not recorded in the instructions, mainly including leukopenia, abdominal distension, fever, dysbacteriosis, etc. The latency of adverse reactions ranged from 5 min to 65 days, with a median time of 5 days. The grade of adverse reactions was general in 379 patients (92.89%) and severe in 29 patients (7.11%). The top 3 SOCs involved in 53 case times of severe adverse reactions were hepatobiliary diseases (30 case times, 56.60%), vascular, bleeding and coagulation diseases (8 case times, 15.09%), and urinary tract diseases (4 case times, 7.55%), the main clinical manifestations were elevated liver enzymes, coagulation disorders, pancreatitis, etc. After the occurrence of adverse reactions, all patients stopped tigecycline, and received symptomatic treatments such as liver protection, intravenous infusion of human fibrinogen, intravenous infusion of platelets, and antidiarrheal therapy. Among 408 patients, 66 (16.18%) were cured, 297 (72.79%) were improved, 20 (4.90%) were not improved, and 25 cases' outcome (6.13%) were unknown. The shortest time for recovery or improvement was 0.5 hour, the longest was 44 days, with a median time of 5 days. The correlation between tigecycline and adverse reactions was probable in 132 patients (32.35%), and possible in 276 patients (67.65%). Conclusions:Tigecycline-related adverse reactions involve multiple organ systems, mainly including gastrointestinal diseases, vascular, bleeding and coagulation diseases, and hepatobiliary diseases, etc. which can lead to severe adverse reactions such as acute pancreatitis and coagulation disorders. After drug withdrawal and symptomatic treatments, most patients had a good prognosis.

Objective:To investigate the magnetic resonance imaging (MRI) features of pediatric and adolescent mediastinal T-lymphoblastic lymphoma (T-LBL) and to evaluate their predictive value for early treatment response.Methods:A retrospective, multicenter case series study was conducted on 49 pediatric and adolescent patients diagnosed with mediastinal T-LBL between September 2020 and May 2024 at the Fifth Affiliated Hospital of Zhengzhou University, Beijing Gaobo Boren Hospital, and Henan Cancer Hospital.All patients underwent chest MRI, including conventional MRI sequences and diffusion-weighted imaging.Tumor imaging characteristics were analyzed, and quantitative parameters such as minimum apparent diffusion coefficient (ADCmin), maximum ADC (ADCmax), and mean ADC (ADCmean) were measured.Treatment response was evaluated 15 days post-treatment.The patients were divided into a response group (complete or partial response, 26 cases) and a non-response group (progressive disease or minor response, 23 cases).The relationship between MRI features and treatment response was analyzed.The intraclass correlation coefficient was used to assess inter-reader agreement, and independent sample t-tests and chi-square tests were employed to compare differences between groups.Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of imaging parameters. Results:Significant differences were observed between the response and non-response groups in ADC values [ADCmin (0.80±0.41)×10 -3 mm 2/s vs.(1.23±0.70)×10 -3 mm 2/s, ADCmax (1.14±0.48)×10 -3 mm 2/s vs.(1.92±0.77)×10 -3 mm 2/s, ADCmean (0.98±0.42)×10 -3 mm 2/s vs.(1.56±0.74)×10 -3 mm 2/s] and the maximum tumor diameter was [(11.92±3.61) cm vs.(8.17±2.46) cm] (all P<0.05).ROC curve analysis showed that ADCmax had the highest predictive efficiency for treatment response, with an area under the curve (AUC) of 0.853 (95% CI: 0.790-0.910), sensitivity of 92.3%, and specificity of 65.2%.The AUC for the maximum tumor diameter was 0.814, demonstrating its excellent predictive performance. Conclusions:MRI features, particularly ADC values and the maximum tumor diameter, can effectively predict treatment response in pediatric and adolescent mediastinal T-LBL.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective To analyze the distribution characteristics and influencing factors of ultra-long hospitalization in malignant tumor patients and to explore strategies to reduce the average length of stay and enhance the efficiency of medical re-source utilization.Methods Ultra-long hospitalization was defined as the 99th percentile of hospital stay duration(P99=31 days).Data from patients discharged with malignant tumors in a specialized cancer hospital in 2024 were collected.The distribu-tion characteristics and influencing factors were analyzed using chi-square tests and logistic stepwise regression.Results Among the 36 097 patients with malignant tumors,the average length of stay was 4.95 days,with 375 cases classified as ultra-long hospi-talizations,accounting for 1.04％.These patients were predominantly over 55 years old,with a higher proportion of males.Pa-tients with stage Ⅲ malignant tumors,primary tumors classified as T2～T3,and primary sites in the esophagus,pancreas,and maxillofacial regions had a higher incidence of ultra-long hospitalizations.Significant factors influencing ultra-long hospitalization included treatment modality,complications(OR=20.319),number of discharge diagnoses(OR=6.915),ICU transfers(OR=4.714),unplanned reoperations(OR=4.416),tumor type,extent,and stage.Conclusion Medical institutions are advised to address the influencing factors of ultra-long hospitalizations by optimizing diagnostic and treatment processes,enhan-cing quality control systems,establishing early warning mechanisms,and strengthening information systems.These measures aim to improve the standardization of malignant tumor diagnosis and treatment,ensuring patient safety.

A quadruplex RT-qPCR method was developed for rapid identification and diagnosis of transmissible gastroenteritis virus(TGEV)of swine,porcine epidemic diarrhea virus(PEDV),porcine deltacorona virus(PDCoV),and porcine rotavirus type A(PoRVA).The full-length sequences of PEDV(77 strains),TGEV(63 strains),PDCoV(17 strains)that are prevalent in China,as well as the 85 VP6 gene sequences of PoRVA,were downloaded from the NCBI database for homology analysis.Based on the relatively conserved sequences,the corresponding primers and probes for each virus were designed and used to establish the quadruplex RT-qPCR method.After optimization of the probes and the reaction conditions,the specificity,sensitivity,and repeatability were determined.Using the established method,109 clinical samples of diarrhea were tested and further compared with the results by standard method.The results showed that the quadruplex RT-qPCR method established in this experiment has good amplification effect,with the C,value linearly correlated with the copies of templates(R2＞0.99).Specificity assay demonstrated that the quadruplex RT-qPCR method can identify TGEV,PEDV,PDCoV,PRoVA strains,and do not de-tect African swine fever virus(ASFV),porcine circovirus type 2(PCV2),porcine reproductive and respiratory syndrome virus(PRRSV),classical swine fever virus(CSFV),pseudorabies virus(PRV)and other epidemic viruses.Sensitivity assay showed that the detection limits for TGEV,PEDV,PDCoV and PoRVA were 10,20,20 and 50 copies/μL,respectively.The method exhibits excellent reproducibility,with coefficients of variation(Cv)for both intra-and inter-assay repli-cates being less than 1％.Detection of 109 samples of diarrhea by this method yielded the coinci-dence rate of 100％with the industry standard,indicating high practical applicability.The devel-oped method possesses the advantages of strong strain compatibility,high sensitivity,strong speci-ficity,good repeatability and stability.It is suitable for virus diagnosis and large-scale clinical sam-ple testing,providing technical support for disease prevention and control as well as epidemiologi-cal investigation.

The objective of this study was to develop a rapid and precise detection technique for por-cine Senecavirus A(SVA)employing reverse transcription recombinase polymerase amplification(RT-RAA)in conjunction with CRISPR Cas13a technology.Additionally,the study aimed to opti-mize the assay's reaction conditions to enhance amplification efficiency.Eight RT-RAA primer sets were designed based on the conserved gene sequence of porcine SVA,and a series of reaction condi-tions were evaluated to refine the RT-RAA reaction system.Subsequently,CRISPR-derived RNA(crRNA)sequences were developed and selected to construct the RT-RAA-CRISPR reaction sys-tem.The method's specificity was determined by examining six prevalent porcine pathogenic nucleic acids,while its sensitivity was assessed using SVA cRNA standards quantified by digital PCR.The method's stability and the consistency of clinical sample analysis were also evaluated.The findings revealed that the optimized RT-RAA and CRISPR reaction systems exhibited the highest amplifi-cation efficiency at a reaction temperature of 37 ℃.Among the eight crRNAs,five were identified as exhibiting the strongest detection signals.The formulated RT-RAA-CRISPR Cas13a method demonstrated exceptional specificity,showing no cross-reactivity with other common porcine disea-ses,including ASFV,PRRSV,PEDV,PCV2,CSFV,and PRV.The method achieved high sensitivi-ty,detecting as low as 0.86 copies/μL of SVA,and exhibited stable fluorescence output,robust re-producibility,and the ability to complete clinical sample analysis within 50 minutes.Consistency e-valuation with six positive and 58 negative samples indicated 100％agreement in outcomes.These results substantiate that the study successfully established a rapid and specific RT-RAA-CRISPR Cas13a detection method for the on-site identification of porcine Senecavirus A,demonstrating high specificity and sensitivity,and holds promise for application in SVA monitoring and control initia-tives.

This study aims to investigate the therapeutic effect and mechanism of Daotan Xixin Decoction on APP/PS1 mice. Twelve APP/PS1 male mice were randomized into four groups: APP/PS1 and low-, medium-, and high-dose Daotan Xixin Decoction. Three C57BL/6 wild-type mice were used as the control group. The learning and memory abilities of mice in each group were examined by the Morris water maze test. The pathological changes of hippocampal nerve cells were observed by hematoxylin-eosin staining and Nissl staining. Immunohistochemistry was employed to detect the expression of β-amyloid(Aβ)_(1-42) in the hippocampal tissue. The high-dose Daotan Xixin Decoction group with significant therapeutic effects and the model group were selected for high-throughput sequencing. The differentially expressed gene(DEG) analysis, Gene Ontology(GO) analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and Gene Set Variation Analysis(GSVA) were performed on the sequencing results. RT-qPCR and Western blot were conducted to determine the mRNA and protein levels, respectively, of some DEGs. Compared with the APP/PS1 group, Daotan Xixin Decoction at different doses significantly improved the learning and memory abilities of APP/PS1 mice, ameliorated the neuropathological damage in the CA1 region of the hippocampus, increased the number of neurons, and decreased the deposition of Aβ_(1-42) in the brain. A total of 1 240 DEGs were screened out, including 634 genes with up-regulated expression and 606 genes with down-regulated expression. The GO analysis predicted the biological processes including RNA splicing and protein folding, the cellular components including spliceosome complexes and nuclear spots, and the molecular functions including unfolded protein binding and heat shock protein binding. The KEGG pathway enrichment analysis revealed the involvement of neurodegenerative disease pathways, amyotrophic lateral sclerosis, and splicing complexes. Further GSVA pathway enrichment analysis showed that the down-regulated pathways involved nuclear factor-κB(NF-κB)-mediated tumor necrosis factor-α(TNF-α) signaling pathway, UV response, and unfolded protein response, while the up-regulated pathways involved the Wnt/β-catenin signaling pathway. The results of RT-qPCR and Western blot showed that compared with the APP/PS1 group, Daotan Xixin Decoction at different doses down-regulated the mRNA and protein levels of signal transducer and activator of transcription 3(STAT3), NF-κB, and interleukin-6(IL-6) in the hippocampus. In conclusion, Daotan Xixin Decoction can improve the learning and memory abilities of APP/PS1 mice by regulating the STAT3/NF-κB/IL-6 signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Male ; Alzheimer Disease/metabolism* ; Computational Biology ; Mice, Inbred C57BL ; High-Throughput Nucleotide Sequencing ; Amyloid beta-Protein Precursor/metabolism* ; Hippocampus/metabolism* ; Mice, Transgenic ; Presenilin-1/metabolism* ; Humans ; Memory/drug effects* ; Maze Learning/drug effects* ; Amyloid beta-Peptides/genetics* ; Disease Models, Animal