With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

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.

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.

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 investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Objective To elucidate the effect of Deduhonghua-7 powder and its main components on liver fibrosis induced by carbon tetrachloride(CCl4)by regulating chemokine receptor 1(CCR1)and DNA methyltransferase 1(DNMT1).Methods C57BL/6 mice were randomly divided into blank group,model group,Deduhonghua-7 powder group(0.75 g·kg-1 Deduhonghua-7 powder),Scabiosa Atropurea group(0.75 g·kg-1 Scabiosa Atropurea)and Luteolin-L,-H groups(0.02 and 0.04 g·kg-1 Luteolin,respectively).Except the blank group,the other groups were intrabitoneally injected with 10％CC14 olive oil solution to establish liver fibrosis model,and all groups were given 0.5％CMC-Na dissolved intragastric drug once a day for 4 weeks,and blood and liver tissues were collected after the last administration.The serum CCR1,DNMT1,α-smooth muscle actin(α-smA)and precollagen Ⅲ contents were detected by enzyme linked immunosorbent assay;the CCR1,DNMT1,α-smA,Collagen Ⅰprotein expression were detected by Western blot.Result The contents of serum DNMT1 in blank group,model group,Deduhonghua-7 powder group,Luteotin-L,-H groups and Scabiosa Atropurea group were(4.56±0.69),(6.09±0.59),(5.21±0.33),(4.99±0.68),(5.03±0.45)and(5.17±0.61)pg·mL-1;the contents of CCR1 were(13.38±0.47),(11.20±0.73),(12.97±0.80),(12.89±0.75)(12.88±0.95)and(12.92±0.58)pg·mL-1;the contents of α-smA were(181.80±24.50),(281.30±26.60),(220.90±22.30),(193.70±16.10),(199.30±17.70)and(205.80±14.70)pg·mL-1;the contents of procollagen Ⅲ were(49.29±8.26),(77.56±8.61),(67.56±5.63),(55.47±7.07),(64.93±8.66)and(59.66±8.51)pg·mL-1;the relative expression levels of DNMT1 protein in liver tissues were 0.08±0.03,0.26±0.08,0.13±0.01,0.12±0.05,0.13±0.05 and 0.15±0.03;the CCR1 protein relative expression levels were 0.18±0.03,0.13±0.02,0.21±0.06,0.22±0.07,0.17±0.07 and 0.18±0.06;the α-smA protein relative expression levels were 0.03±0.01,0.27±0.11,0.09±0.05,0.12±0.08,0.09±0.07 and 0.11±0.07;the expression of Colagen Ⅰ protein were 0.09±0.04,0.65±0.22,0.28±0.12,0.26±0.19,0.30±0.22 and 0.25±0.12.The differences of above indicators between the model group and the blank group,between the Deduhonghua-7 powder group,Luteotin-L,-H groups,Scabiosa Atropurea group and the model group were statistically significant(all P＜0.05).Conclusion Luteotein is one of the pharmacodynamic substance bases of Deduhonghua-7 powder to alleviate liver fibrosis induced by CC14.It can inhibit or delay the formation of liver fibrosis through CCR1,DNMT1,α-smA and Collagen Ⅰ proteins.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Purpose::Shaping and assembling contemporary external fixators rapidly for the severe mandibular fractures remains a challenge, especially in emergency circumstance. We designed a novel external fixator that incorporates universal joints to provide the stabilization for mandibular comminuted fractures. This study aims to confirm the efficacy of this novel external fixator through biomechanical tests in vitro and animal experiments. Methods::In vitro biomechanical tests were conducted using 6 fresh canine with mandibular defect to simulate critical comminuted fractures. Three mandibles were stabilized by the novel external fixator and other mandibles were fixed by 2.5 mm reconstruction plates. All fixed mandibles were subjected to loads of 350 N on the anterior regions of teeth and 550 N on the first molar of the unaffected side. The stability was evaluated based on the maximum displacement and the slope of the load-displacement curve. In animal experiments, 9 beagles with comminuted mandibular fractures were divided into 3 groups, which were treated with the novel external fixation, reconstruction plate, and dental arch bar, respectively. The general observation, the changes in animals’ weight, and the surgical duration were recorded and compared among 3 groups. The CT scans were performed at various intervals of 0 day (immediately after the surgery), 3 days, 7 days, 14 days, 21 days, and 28 days to analyze the displacement of feature points on the canine mandible and situation of fracture healing at 28 days. The statistical significance was assessed by the two-way analysis of variance test followed by the Bonferroni test, enabling multiple comparisons for all tests using GraphPad Prism10.1.0 (GraphPad Inc, USA). Results::The outcomes of the biomechanical tests indicated that no statistically significant differences were found in terms of the maximum displacement ( p = 0.496, 0.079) and the slope of load displacement curves ( p = 0.374, 0.349) under 2 load modes between the external and internal fixation groups. The animal experiment data showed that there were minor displacements of feature points between the external and internal fixation groups without statistic difference, while the arch bar group demonstrated inferior stability. The CT analysis revealed that the best fracture healing happened in the internal fixation group, followed by the external fixation and arch baring at 28 days after fixation. The external fixation group had the shortest fixation duration (25.67 ± 3.79) min compared to internal fixation ((70.67 ± 4.51) min, p < 0.001) and arch baring ((42.00 ± 3.00) min, p = 0.046). Conclusion::The conclusion of this study highlighted the efficacy and reliability of this novel external fixator in managing mandibular fractures rapidly, offering a viable option for the initial stabilization of comminuted mandibular fractures in the setting of emergency rescue.

Objective To develop a rapid and accurate Monte Carlo program(simplified code for dosimetry of carbon ions,SPEEDO)for carbon ion therapy.Methods For electromagnetic process,type Ⅱ condensed history simulation scheme and continuous slowing down approximation were used to simulate energy straggling,range straggling,multiple scattering,and ionization processes.For nuclear interaction,5 types of target nuclei were considered,including hydrogen,carbon,nitrogen,oxygen,and calcium.The produced secondary charged particles followed the same condensed history framework.The study simulated the transport of carbon ions in 4 materials(water,soft tissues,lung,and bone),and the calculated doses were validated against TOPAS(a Monte Carlo simulation software for radiotherapy physics),followed by a comparison with dose measurements in a water phantom from the HIMM-WW(a medical heavy-ion accelerator facility in Wuwei).Results SPEEDO's simulation results showed good consistency with TOPAS.For each material,in the voxel region where the physical dose was greater than 10％of the maximum dose point,the relative maximum dose error of both was less than 2％.At treatment energy of 400 MeV/u,SPEEDO's computation time was significantly less than that of TOPAS(13.8 min vs 105.0 min).SPEEDO's calculation results also showed good agreement with HIMM-WW measurements in terms of lateral dose distribution and integrated dose depth curve.Conclusion SPEEDO program can accurately and rapidly perform Monte Carlo dose calculations for carbon-ion therapy.

Objective:To evaluate the correlation between the degree of posterior longitudinal ligament (PLL) injury and various parameters of vertebral body injury in patients with thoracolumbar burst fractures.Methods:A total of 48 patients with thoracolumbar burst fractures were admitted to the Spine Surgery Center of the Second Affiliated Hospital of Inner Mongolia Medical University between December 2022 and January 2024. The cohort consisted of 31 males and 17 females, with a mean age of 44.1±11.8 years (range, 18-65 years). Based on the PLL injury grading method proposed by Sun Zhaoyun, patients were classified into three groups: mild, moderate, and severe. However, due to an insufficient number of patients in the severe group ( n=3), the moderate and severe groups were combined for statistical analysis, resulting in two groups: mild, and moderate-to-severe. Patient demographic and clinical data were collected. Local kyphosis (LK), inversion angle (IA), horizontal rotation angle (HRA), increased interspinous distance (IISD), anterior vertebral body compression ratio (AVBCR), posterior vertebral body compression ratio (PVBCR), middle vertebral body compression ratio (MVBCR), the ratio of height of bone fragment (RHBF), the ratio of width of bone fragment (RWBF), and mid-sagittal canal diameter compression ratio (MSDCR) were measured. Statistical analyses were performed using SPSS 25.0. Categorical variables were expressed as frequency (percentage) and analyzed using chi-square and Fisher exact tests. Continuous variables were tested for normality, with non-normally distributed data analyzed using the rank-sum test and expressed as median (interquartile range). Multivariate logistic regression analysis was performed to identify independent risk factors, and receiver operating characteristic (ROC) curves were plotted to calculate the area under the curve (AUC) to evaluate predictive performance. Results:Among the 48 patients, only 3 were found to have severe PLL injury, necessitating the combination of the moderate and severe groups for statistical purposes. Patients in the moderate-to-severe group demonstrated significantly higher AVBCR, PVBCR, RHBF, MVBCR, MSDCR, and IA compared to the mild group ( P<0.05). Multivariate logistic regression identified AVBCR, PVBCR, MSDCR, and IA as independent risk factors for moderate-to-severe PLL injury ( OR>1, P<0.05). ROC curve analysis revealed that AVBCR, PVBCR, MSDCR, IA, and their combined index could effectively predict moderate-to-severe PLL injury ( P<0.05). Notably, the combined index showed superior predictive performance (AUC=0.970) compared to individual parameters. Threshold values were determined as follows: AVBCR>45.30%, PVBCR>12.17%, MSDCR>27.13%, IA>5.90°, and the combined index >0.61, indicating PLL damage. Conclusion:AVBCR, PVBCR, MSDCR, IA, and their combined index are significantly associated with moderate-to-severe PLL injury in thoracolumbar burst fractures. The combined index demonstrates superior predictive ability compared to single parameters, providing a reliable tool for assessing PLL integrity.