Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

Objective To investigate the effects of insulin-like growth factor binding protein 7(IGFBP7)on the sensitivity of glioma cells to temozolomide(TMZ)and the related mechanism.Methods IGFBP7 mRNA expression levels in TMZ-sensitive(U87 TMZ-S,U251 TMZ-S)and TMZ-resistant(U87 TMZ-R,U251 TMZ-R)glioma cells were analyzed using RNA sequencing data from the gene expression omnibus(GEO)dataset GSE151680.TMZ-resistant U87 and U251 cell lines were established via stepwise dose escalation.IGFBP7 expressions in TMZ-R cells were detected by quantitative real-time PCR(qPCR)and Western blotting.IGFBP7 was stably knock-downed in TMZ-R cells while IGFBP7 was stably overexpressed in TMZ-S cells using lentiviral infection.Cell viability,migration,invasion and TMZ sensitivity were assessed using CCK-8 assay,apoptosis assay,wound healing assay,Transwell invasion assay and colony formation assay respectively.Cellular senescence was detected by β-galactosidase(SA-β-Gal)staining.The expression levels of senescence molecular markers cyclin-dependent kinase inhibitor 1(p21)and tumor protein p53(p53),as well as DNA damage marker γ-H2A histone family member X(γ-H2AX)were determined by Western blotting.The differences in mRNA expressions of IGFBP7 between glioma tissues and normal tissues as well as the correlations with the overall survival of glioma patients were analyzed using the cancer genome atlas(TCGA),Chinese Glioma Genome Atlas(CGGA),genotype-tissue expression(GTEx)database.Results Compared to normal glioma cells,IGFBP7 expressions were significantly elevated in TMZ-R glioma cells.Overexpression of IGFBP7 in TMZ-S glioma cells enhanced cell viability but suppressed apoptosis following TMZ treatment.The expressions of senescence-associated marker(p21,p53)and DNA damage marker(γ-H2AX)were upregulated in these cells.Notably,IGFBP7 expressions were significantly higher in glioma tissues than in normal tissues,and high IGFBP7 expressions were associated with poor prognosis in glioma patients.Conclusion Knockdown of IGFBP7 promotes TMZ-induced cell senescence and DNA damage,thereby enhancing the sensitivity of gliomas cells to TMZ.

Objective: To analyze the characteristics and trends of drowning mortality among Chinese residents from 2010 to 2021, so as to provide a basis for developing targeted prevention strategies and reducing the burden of drowning deaths. Methods: Data on drowning mortality among Chinese residents from 2010 to 2021 were collected from the China Cause of Death Surveillance Dataset (2010-2021). The crude mortality was calculated and then standardized using the data from the Sixth National Population Census in 2010. The characteristics of drowning mortality were analyzed by genders, regions, and ages. The average annual percent change (AAPC) was employed to assess the trend in drowning mortality. Results: From 2010 to 2021, the overall crude drowning mortality among Chinese residents was 3.53/100 000, with a standardized mortality of 3.34/100 000, both showed decreasing trends (AAPC=-2.438% and -3.739%, both P<0.05). The crude and standardized mortality were higher in males than in females (4.55/100 000 vs. 2.47/100 000, 4.43/100 000 vs. 2.16/100 000, both P<0.05). Both the crude drowning mortality (AAPC=-2.974% and -1.337%) and standardized drowning mortality (AAPC=-3.806% and -3.599%) among males and females showed decreasing trends, respectively (all P<0.05). The crude and standardized drowning mortality were higher in rural residents than in urban residents (4.13/100 000 vs. 2.35/100 000, 3.86/100 000 vs. 2.27/100 000, both P<0.05). Both the crude and standardized drowning mortality in rural residents showed decreasing trends (AAPC=-3.343% and -4.515%, both P<0.05), whereas no statistically significant trends were observed in urban residents (both P>0.05). Both the crude and standardized drowning mortality were higher in western residents than in eastern residents and central residents (4.30/100 000 vs. 2.89/100 000 and 3.66/100 000, 4.14/100 000 vs. 2.64/100 000 and 3.49/100 000, all P<0.05). The standardized mortality showed decreasing trends in eastern, central and western residents (AAPC=-3.237%, -2.344%, and -5.467%, all P<0.05). The groups aged ≥65 years and 1-<5 years experienced relatively high crude drowning mortality of 8.81/105 and 7.38/105, respectively. Decreasing trends were observed in groups aged <1 year, 1-<5 years, and 5-<15 years (AAPC=-14.126%, -11.452%, and -7.443%, all P<0.05). In contrast, no statistically significant trends were observed in the other age groups (all P>0.05). Conclusions The overall drowning mortality rate among Chinese residents showed a declining trend from 2010 to 2021. However, the risks of drowning mortality remained relatively high among males, rural residents, residents in the western region, children, and the elderly.

Nucleic acid elements are essential functional sequences that play critical roles in regulating gene expression, optimizing pathways, and enabling gene editing to enhance the production of target products in biomanufacturing. Therefore, the design and optimization of these elements are crucial in constructing efficient cell factories. Artificial intelligence (AI) provides robust support for biomanufacturing by accurately predicting functional nucleic acid elements, designing and optimizing sequences with quantified functions, and elucidating the operating mechanisms of these elements. In recent years, AI has significantly accelerated the progress in biomanufacturing by reducing experimental workloads through the design and optimization of promoters, ribosome-binding sites, terminators, and their combinations. Despite these advancements, the application of AI in biomanufacturing remains limited due to the complexity of biological systems and the lack of highly quantified training data. This review summarizes the various nucleic acid elements utilized in biomanufacturing, the tools developed for predicting and designing these elements based on AI algorithms, and the case studies showcasing the applications of AI in biomanufacturing. By integrating AI with synthetic biology and high-throughput techniques, we anticipate the development of more efficient tools for designing nucleic acid elements and accelerating the application of AI in biomanufacturing.
Artificial Intelligence ; Synthetic Biology ; Nucleic Acids/genetics* ; Algorithms ; Gene Editing ; Promoter Regions, Genetic ; Biotechnology/methods*

Objective To analyze the value of abdominal CT images combined with serological indicators in predicting the ureteral involvement in idiopathic retroperitoneal fibrosis(IRF). Methods The CT images of 79 IRF patients were analyzed retrospectively,including the involved sites and enhancement characteristics of the lesions.According to the inclusion and exclusion criteria,43 patients with complete serological data were selected and assigned into a ureteral involvement group(n=29)and a non-ureteral involvement group(n=14) according to whether ureters were involved in IRF.Logistic regression analysis was performed to select independent risk factors for ureteral involvement in IRF.The receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of the CT arterial phase enhancement magnitude and serum cystatin C(CysC)for ureteral involvement in IRF. Results The CT images of IRF usually showed a soft tissue density lesion encompassing the abdominal aorta,iliac arteries,ureters,and retroperitoneal tissue,with a wide range of distribution.The ureteral involvement group and the non-ureteral involvement group showed differences in gender(P=0.031),CT arterial phase enhancement amplitude(P=0.014),CT venous phase enhancement amplitude(P=0.032),and serum CysC(P=0.036).Logistic regression analysis showed that gender(P=0.034),CT arterial phase enhancement amplitude(P=0.046),and serum CysC(P=0.041)were independent risk factors for ureteral involvement in IRF.The area under the curve for CT arterial phase enhancement combined with serum CysC to predict ureteral involvement in IRF was 0.776.Ten patients had lower levels of erythrocyte sedimentation rate(P<0.001),C-reactive protein(P=0.021),and IgG4(P<0.001)in the follow-up period than before treatment. Conclusion The combination of abdominal CT images with serological indicators demonstrates high accuracy in predicting the ureteral involvement in IRF,providing reference for early clinical diagnosis.
Humans ; Male ; Female ; Retroperitoneal Fibrosis/pathology* ; Middle Aged ; Retrospective Studies ; Tomography, X-Ray Computed ; Aged ; Adult ; Ureter/diagnostic imaging* ; Predictive Value of Tests ; Cystatin C/blood*

Objective To explore the research progress and hotspots of intelligent ultrasound imaging in the diagnosis of thyroid nodules and clarify the research directions via the bibliometric method.Methods The relevant research articles on intelligent ultrasound imaging in the diagnosis of thyroid nodules were retrieved from the Web of Science Core Collection,covering the period from January 2004 to August 2024.Python was used to analyze the number of annual publications.VOSviewer was used to create the co-occurrence network of authors and the keyword density map.CiteSpace was used to demonstrate the dual-map overlays of the journals,as well as the bursts and clustering of co-citations and keywords.Results A total of 1 179 articles were included.The annual number of publications increased steadily.The involved journals demonstrated high quality,and the publications showed a trend of cross-research.Chinese researchers were the core research force in this field.Haugen et al.'s study on the guidelines for thyroid nodules had the most citations.The clustering of co-citations and keywords indicated studies in multiple fields.Thyroid nodules,cancer,and deep learning were the representative keywords in this field.Conclusions The continuous enrichment of research topics promotes the rapid development of intelligent ultrasound imaging for thyroid nodules.Intelligent diagnosis methods based on deep learning can provide diagnostic suggestions,while there are still challenges such as interpretation.One of the research directions is the deep combination of intelligent diagnosis algorithms and medical knowledge.
Thyroid Nodule/diagnostic imaging* ; Humans ; Ultrasonography ; Bibliometrics

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease worldwide, accounting for 20%-40% of primary glomerulonephritis cases. Approximately 40% of patients progress to end-stage renal disease within 20 years. Traditional treatments primarily involve renin-angiotensin system inhibitors and glucocorticoids, but some patients show limited response and face infection risks. In recent years, the dual-target biologic agent Telitacicept, which targets B cell-activating factor/B lymphocyte stimulator(BAFF/BLyS) and a proliferation-inducing ligand (APRIL), has demonstrated significant potentialin the treatment of IgAN. By simultaneously neutralizing BAFF/BLyS and APRIL, Telitacicept suppresses abnormal B-cell activation and the production of pathogenic IgA1, significantly reducing urinary protein levels and preserving renal function. This article systematically reviews its mechanism of action, clinical efficacy, and safety, aiming to provide insights for the clinical management of IgAN.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective Hypothyroidism is a common clinical disease of systemic metabolic reduction,the incidence and detection rate increased year by year.Based on the clinical characteristics of hypothyroidism,the study constructed and improved animal models to provide reference for the study of hypothyroidism prevention and treatment.Methods By reviewing relevant domestic and foreign literatures,the modeling methods of hypothyroidism were summarized and analyzed.According to the etiology,pathogenesis and clinical diagnostic criteria of hypothyroidism in Chinese medicine and Western medicine,the modeling methods and principles of hypothyroidism animal models were summarized,and the advantages and disadvantages of animal models and the evaluation of clinical conformity were analyzed.Results It was found that the model of drug induction,iodine restriction and 131 I-induced hypothyroidism had high clinical anastomosis in Western medicine,and had the advantages of simple operation,high model formation rate and good repeatability,the combination of the disease model and the syndrome model of kidney yang deficiency and spleen and kidney yang deficiency have a high degree of clinical conformity in TCM.Congenital induced hypothyroidism,autoimmune induced hypothyroidism and genetic induced hypothyroidism can be studied for their unique etiology and pathogenesis,but their clinical manifestations are relatively simple and their clinical anastomosis is relatively low.At present,the construction of hypothyroidism animal model is mainly based on the pathogenesis of Western medicine,and the evaluation of the model mostly relies on laboratory detection indicators.The clinical anastomosis score of traditional Chinese medicine is generally low,and the record of animal apparent indicators is generally insufficient.Conclusion In the process of building hypothyroidism animal model,based on the pathogenesis of traditional Chinese medicine,combining the etiology of traditional Chinese medicine and the pathogenesis of Western medicine,multi-factor comprehensive modeling method can be adopted to increase the record of apparent indicators,improve the accuracy of the four diagnoses and symptoms of traditional Chinese medicine,and systematically and dynamically observe the interaction process of disease and syndrome,so as to build an animal model of hypothyroidism which is more closely aligns with with the clinical characteristics of traditional Chinese medicine and Western medicine.

Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.