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.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

The n-butanol fraction of Alpinia oxyphylla Fructus 70% ethanol extract was separated and purified using column chromatography with MCI Gel CHP-20, Sephadex LH-20, ODS, and silica gel, combined with semi preparative liquid phase and TLC separation methods. One new halogenated 4,5-seco-eudesmane sesquiterpenoid and two new eremophilane sesquiterpenoids were isolated and purified from the n-butanol fraction of Alpinia oxyphylla Fructus. The structures of the isolated compounds were identified using modern spectroscopic methods (1D, 2D NMR, UV, IR, MS, etc.), and the absolute configuration of the new compounds were determined using the methods of calculated ECD and induced ECD.

Objective:To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.Methods:Undergraduates from four classes at Guanghua School of Stomatology, Sun Yat-Sen University were taken as research subjects. Students from two classes ( n=198) were taught using the semi-flipped classroom combined with the knowledge point auction learning method, while students from the other two classes ( n=172) were taught with the regular classroom teaching method as controls. Classroom quizzes were used to compare the two classes' mastery of important and difficult points, and a questionnaire was used to investigate students' feedback on the class outcomes. SPSS 22.0 was used for the independent samples t-test. Results:The mean test score of the experimental class was higher than that of the control class (88.51±11.02 vs. 80.40±8.53). The results of the questionnaire showed that students' interest in the course, comprehension and absorption of knowledge points, degree of satisfaction with the class, and mastery of the contents in sections in the experimental class were significantly higher than those in the control class (7.28±1.51 vs. 9.10±0.73, 6.92±1.44 vs. 8.69±1.62, 6.09±1.87 vs. 7.61±1.46, 6.40±1.04 vs. 7.70±0.86 ).Conclusions:The semi-flipped classroom combined with the knowledge point auction learning method is innovative and achieves good teaching outcomes. It holds promise for wider use in the theoretical teaching of various clinical subjects. To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.

Objective:To investigate the feasibility and accuracy of computer vision-based artificial intelligence technology in detecting and recognizing instruments and organs in the scenario of radical laparoscopic gastrectomy for gastric cancer.Methods:Eight complete laparoscopic distal radical gastrectomy surgery videos were collected from four large tertiary hospitals in China (First Medical Center of Chinese PLA General Hospital [three cases], Liaoning Cancer Hospital [two cases], Liyang Branch of Jiangsu Province People's Hospital [two cases], and Fudan University Shanghai Cancer Center [one case]). PR software was used to extract frames every 5–10 seconds and convert them into image frames. To ensure quality, deduplication was performed manually to remove obvious duplication and blurred image frames. After conversion and deduplication, there were 3369 frame images with a resolution of 1,920×1,080 PPI. LabelMe was used for instance segmentation of the images into the following 23 categories: veins, arteries, sutures, needle holders, ultrasonic knives, suction devices, bleeding, colon, forceps, gallbladder, small gauze, Hem-o-lok, Hem-o-lok appliers, electrocautery hooks, small intestine, hepatogastric ligaments, liver, omentum, pancreas, spleen, surgical staplers, stomach, and trocars. The frame images were randomly allocated to training and validation sets in a 9:1 ratio. The YOLOv8 deep learning framework was used for model training and validation. Precision, recall, average precision (AP), and mean average precision (mAP) were used to evaluate detection and recognition accuracy.Results:The training set contained 3032 frame images comprising 30 895 instance segmentation counts across 23 categories. The validation set contained 337 frame images comprising 3407 instance segmentation counts. The YOLOv8m model was used for training. The loss curve of the training set showed a smooth gradual decrease in loss value as the number of iteration calculations increased. In the training set, the AP values of all 23 categories were above 0.90, with a mAP of 0.99, whereas in the validation set, the mAP of the 23 categories was 0.82. As to individual categories, the AP values for ultrasonic knives, needle holders, forceps, gallbladders, small pieces of gauze, and surgical staplers were 0.96, 0.94, 0.91, 0.91, 0.91, and 0.91, respectively. The model successfully inferred and applied to a 5-minutes video segment of laparoscopic gastroenterostomy suturing.Conclusion:The primary finding of this multicenter study is that computer vision can efficiently, accurately, and in real-time detect organs and instruments in various scenarios of radical laparoscopic gastrectomy for gastric cancer.

Objective:To investigate the feasibility and accuracy of computer vision-based artificial intelligence technology in detecting and recognizing instruments and organs in the scenario of radical laparoscopic gastrectomy for gastric cancer.Methods:Eight complete laparoscopic distal radical gastrectomy surgery videos were collected from four large tertiary hospitals in China (First Medical Center of Chinese PLA General Hospital [three cases], Liaoning Cancer Hospital [two cases], Liyang Branch of Jiangsu Province People's Hospital [two cases], and Fudan University Shanghai Cancer Center [one case]). PR software was used to extract frames every 5–10 seconds and convert them into image frames. To ensure quality, deduplication was performed manually to remove obvious duplication and blurred image frames. After conversion and deduplication, there were 3369 frame images with a resolution of 1,920×1,080 PPI. LabelMe was used for instance segmentation of the images into the following 23 categories: veins, arteries, sutures, needle holders, ultrasonic knives, suction devices, bleeding, colon, forceps, gallbladder, small gauze, Hem-o-lok, Hem-o-lok appliers, electrocautery hooks, small intestine, hepatogastric ligaments, liver, omentum, pancreas, spleen, surgical staplers, stomach, and trocars. The frame images were randomly allocated to training and validation sets in a 9:1 ratio. The YOLOv8 deep learning framework was used for model training and validation. Precision, recall, average precision (AP), and mean average precision (mAP) were used to evaluate detection and recognition accuracy.Results:The training set contained 3032 frame images comprising 30 895 instance segmentation counts across 23 categories. The validation set contained 337 frame images comprising 3407 instance segmentation counts. The YOLOv8m model was used for training. The loss curve of the training set showed a smooth gradual decrease in loss value as the number of iteration calculations increased. In the training set, the AP values of all 23 categories were above 0.90, with a mAP of 0.99, whereas in the validation set, the mAP of the 23 categories was 0.82. As to individual categories, the AP values for ultrasonic knives, needle holders, forceps, gallbladders, small pieces of gauze, and surgical staplers were 0.96, 0.94, 0.91, 0.91, 0.91, and 0.91, respectively. The model successfully inferred and applied to a 5-minutes video segment of laparoscopic gastroenterostomy suturing.Conclusion:The primary finding of this multicenter study is that computer vision can efficiently, accurately, and in real-time detect organs and instruments in various scenarios of radical laparoscopic gastrectomy for gastric cancer.

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 investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia(AML).Methods:The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group,and the children with high-risk AML who received idarubicin regimen were enrolled as controls,and their clinical data were analyzed.Time to bone marrow recovery,the complete remission rate of bone marrow cytology,the clearance rate of minimal residual disease,and treatment-related adverse reactions were compared between the two groups.Results:The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day),granulocytes(18 vs 24 day),platelets(17 vs 24 day),and hemoglobin(20 vs 26 day)compared with those treated with idarubicin,there were statistical differences(P＜0.05).The effective rate and MRD turning negative rate in the observation group were 90.9％and 72.7％,respectively,while those in the control group were 94.1％and 76.4％,with no statistical difference(P＞0.05).The overall response rate of the two groups of patients was similar.Conclusion:The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML,but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.

Objective:To investigate the prognostic value of minimal residual disease(MRD)detected by multi-parameter flow cytometry(MFC)in pediatric patients with acute myeloid leukemia(AML)after induction chemotherapy.Methods:A retrospective study was conducted on 97 pediatric patients initially diagnosed with AML at Wuhan Children's Hospital from August 2015 to December 2022.The study analyzed the results of MRD detection using MFC after the first and second cycles of induction chemotherapy,and its association with prognosis were analyzed.Results:Following the first cycle of induction treatment,57 of the 97 patients tested positive for MRD(MRD1+,58.8％).Subsequently,19 patients remained MRD positive(MRD2+,19.6％)after the second cycle of induction treatment.Kaplan-Meier survival analysis showed that the estimated 3-year overall survival(OS)rate of the 37(64.9％)MRD1+patients who underwent transplantation was significantly higher than that of the 20(35.1％)MRD1+patients who did not undergo transplantation(84.6％vs 40.0％,P=0.0001).Among the 35 MRD1+MRD2-patients,the 3-year OS rate of the 25 children who underwent transplantation was higher than that of the 10 children who did not undergo transplantation(87.2％vs 70.0％,P=0.3229).The 3-year OS rate of the 19 MRD1+MRD2+patients was lower than that of the 35 MRD1+MRD2-patients(57.4％vs 81.8％,P=0.059).In the 19 MRD2+patients,the 3-year OS rate of the 12 children who underwent transplantation was significantly higher than that of the 7 children who did not undergo transplantation(80.8％vs 14.3％,P=0.0007).There was no significant difference in 3-year OS between the 12 MRD1+MRD2+patients and 25 MRD1+MRD2-patients,both treated with transplantation(80.8％vs 87.2％,P=0.8868).In those not treated with transplantation,the 7 MRD1+MRD2+patients had a significantly lower 3-year OS compared with the 10 MRD1+MRD2-patients(14.3％vs 70.7％,P=0.0114).Further multivariate analysis indicated that MRD2 positivity and transplantation were both independent prognostic factors(P=0.031,0.000),while MRD1 positivity was not significantly associated with the overall prognosis of 97 patients(P=0.902).Conclusion:MRD positivity following the second cycle of induction chemotherapy is an independent risk factor for unfavorable outcomes in children with AML.MRD2 positivity indicates a poorer prognosis and can help to identify the candidates requiring transplantation.MRD2 positivity is not a contraindication for transplantation in pediatric patients,and early transplantation significantly improves the prognosis of high-risk patients.

Objective:To investigate the efficacy and safety of ixazomib combined with thalidomide and dexamethasone in the treatment of multiple myeloma(MM).Methods:The clinical data of 60 MM patients admitted to our center from January 2019 to June 2022 were analyzed retrospectively,including 43 newly diagnosed patients and 17 patients with recurrence and progression.All patients were treated with ixazomib combined with thalidomide and dexamethasone,and completed 2 to 7 treatment cycles.Results:The overall response rate(ORR)of all patients was 98.3％.Among them,53 patients completed 4 treatment cycles,and the ORR was 86.8％.Seventeen patients completed the whole treatment cycle,with curative effect reaching 88.2％achieving very good partial response and above,and 52.9％achieving complete response and above.Albumin and β2-microglobulin of all patients had been improved rapidly after treatment.The deadline was August 31,2022.The median follow-up time was 14(3-24)months,and overall survival(OS)rate was 86.67％.The OS rate of patients with recurrence and progression was significantly lower than that of newly diagnosed patients(P＜0.05).The most common adverse reaction of hematology was lymphopenia(53.3％),followed by anemia(33.3％).The most common non-hematological adverse reaction was fatigue(68.33％),followed by peripheral neuropathy(31.67％).Conclusion:Ixazomib combined with thalidomide and dexamethasone is effective in the treatment of MM,with good short-term efficacy,survival and safety.However,its long-term efficacy needs further observation.