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 To explore the relationship between levels of vascular endothelial growth factor(VEGF),insulin-like growth factor 1(IGF-1),and transforming growth factor-β1(TGF-β1)in the synovial fluid of children with avascular necrosis of the femoral head(also known as Perthes disease)and the efficacy of postoperative revascularization,aiming to provide a basis for subsequent diagnosis and treatment.Methods A retrospective study was conducted on 262 children with Perthes disease admitted to the Affiliated Hospital of Gansu University of Chinese Medicine from January 2023 to June 2024.Based on postoperative revascularization efficacy,patients were divided into good revascularization group(n=228)and poor revascularization group(n=34).For poor revascularization group,a 1:2 matched case-control design was used to select 68 age-matched children with hip synovitis who underwent hip joint fluid puncture as control group.Additionally,82 children with Perthes disease treated at the hospital from June 2024 to January 2025 were enrolled as a validation cohort for nomogram model verification.The expression levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of three groups were compared.Confounding biases were controlled through univariate and stratified analyses.Binary logistic regression analysis was used to identify independent factors affecting the revascularization effect.R software was utilized to draw and verify the nomogram model for predicting the postoperative revascularization effect.Results The levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children in poor revascularization group were all higher than those in control group and good revascularization group(P<0.05).After three types of reconstructive surgeries,the levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children with poor revascularization were all higher than those in children with good revascularization(P<0.05);however,there was no statistically significant difference in the above indicators among different surgical types(P>0.05).Binary logistic regression analysis showed that the levels of VEGF,IGF-1,and TGF-β1 in the synovial fluid were independent risk factors for poor postoperative revascularization in children with Perthes disease.The area under the ROC curve of the nomogram model established accordingly for predicting poor postoperative revascularization in children with Perthes disease was 0.875(95%CI 0.805-0.945),with a sensitivity of 0.874 and a specificity of 0.851.Moreover,the calibration curve and decision curve analysis(DCA)indicated that the model had good clinical applicability.Conclusions The increased levels of VEGF,IGF-1 and TGF-β1 in synovial fluid are associated with poor postoperative revascularization in children with Perthes disease.These three factors are expected to become prognostic indicators for children with Perthes disease.

Urticaria is a common allergic skin disease.Professor FAN Rui-Qiang believes that the main pathogenesis of urticaria is due to endowment intolerance,and wind-pathogen is the main pathogenic factor.The patients of Lingnan area are prone to be attacked by dampness interweaved with heat.The common syndrome patterns of urticaria are wind-damp heat syndrome,spleen deficiency and dampness accumulation syndrome,and disharmony between nutritive qi and defensive qi syndrome.For the treatment of urticaria by stages,the differentiation of deficiency and excess is stressed.Acute urticaria usually manifests as excess syndrome,and chronic urticaria often manifests as deficiency syndrome or deficiency interweaved with excess syndrome.For the treatment of urticaria patients with excess syndrome,therapies of clearing heat and removing dampness,and dispelling wind and relieving itching are recommended,and the modified prescription of Soufeng Lishi Decoction is usually adopted.For the treatment of urticaria patients with deficiency interweaved with excess syndrome,simultaneous treatment of symptoms and root causes should be performed,therapies of invigorating spleen,resolving dampness and relieving itching are recommended,and the modified prescription of Duopi Decoction is adopted.For the treatment of urticaria patients with deficiency syndrome,therapies of regulating nutritive qi and defensive qi,and expelling wind to relieve itching are recommended,and the modified prescription of Yupingfeng Powder plus Guizhi Decoction is adopted.The high-frequency Chinese medicinals for the treatment of urticaria treated by Professor FAN Rui-Qiang are Saposhnikoviae Radix,Cynanchi Paniculati Radix et Rhizoma,Schizonepetae Spica,Glycyrrhizae Radix et Rhizoma,Albiziae Cortex,Artemisiae Scopariae Herba,Paeoniae Radix Alba,Forsythiae Fructus,Tribuli Fructus,Houttuyniae Herba,Rehmanniae Radix,Dictamni Cortex,Atractylodis Rhizoma,Poria,and Astragali Radix.Professor FAN Rui-Qiang's clinical medication is flexible,and aims to reduce recurrence and improve the quality of life of urticaria patients.

Objective To construct an artificial intelligence assisted diagnosis model based on deep learning for dynamically recognizing gastric lesions and their locations under gastroscopy in real time,and to evaluate its ability to detect and recognize gastric lesions and their locations.Methods The gastroscopy videos of 104 patients in our hospital was retrospectively analyzed,and the video frames were manually annotated.The annotated picture frames of lesion category were divided into the training set and the validation set according to the ratio of 8∶2,and the annotated picture frames of location category were divided into the training set and the validation set according to the patient sources at the ratio of 8∶2.These sets were utilized for training and validating the respective models.YoloV4 model was used for the training of lesion recognition,and ResNet152 model was used for the training of location recognition.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value and location recognition accuracy of the auxiliary diagnostic model were evaluated.Results A total of 68 351 image frames were annotated,with 54 872 frames used as the training set,including 41 692 frames for lesion categories and 13 180 frames for location categories.The validation set consisted of 13 479 frames,comprising 10 422 frames for lesion categories and 3 057 frames for location categories.The lesion recognition model achieved an overall accuracy of 98.8%,with a sensitivity of 96.6%,specificity of 99.3%,positive predictive value of 96.3%,and negative predictive value of 99.3% in validation set.Meanwhile,the location recognition model demonstrated an top-5 accuracy of 87.1% .Conclusion The artificial intelligence assisted diagnosis model based on deep learning for real-time dynamic recognition of gastric lesions and their locations under gastroscopy has good ability in lesion detection and location recognition,and has great clinical application prospects.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Humans ; Fusobacterium nucleatum/metabolism* ; NF-kappa B/metabolism* ; Periodontal Ligament/metabolism* ; Signal Transduction ; Fusobacterium Infections/pathology* ; Stem Cells/metabolism*

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.
Child ; Humans ; Infant ; Hepatitis B Vaccines ; Immunization, Secondary ; Hepatitis B Surface Antigens ; Immunologic Memory ; Follow-Up Studies ; Vaccination ; Hepatitis B/prevention & control* ; Hepatitis B Antibodies

During the global efforts to prevent and control the COVID-19 pandemic, extensive research and development of SARS-CoV-2 vaccines using various technical approaches have taken place. Among these, vaccines based on adenovirus vector have gained substantial knowledge and experience in effectively combating potential emerging infectious diseases, while also providing novel ideas and methodologies for vaccine research and development (R&D). This comprehensive review focuses on the adenovirus vector technology platform in vaccine R&D, emphasizing the importance of mucosal immunity induced by adenoviral vector-based vaccine for COVID-19 prevention. Furthermore, it analyzes the key technical challenges and obstacles encountered in the development of vaccines based on the adenovirus vector technology platform, with the aim of providing valuable insights and references for researchers and professionals in related fields.
Humans ; COVID-19 Vaccines ; Pandemics/prevention & control* ; COVID-19/prevention & control* ; SARS-CoV-2/genetics* ; Viral Vaccines/genetics* ; Adenoviridae/genetics* ; Technology

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

Humans ; Universities ; Vaccines ; Bacterial Infections

Objective: To analyze the utilization of adult vaccination among people aged 18 and above in Shandong Province from 2018 to 2022. Methods: Data on vaccination units in 2022 and individual cases of vaccination information for people aged 18 and above were extracted from the Shandong Immunization Information System. A descriptive analysis was conducted on the distribution of adult vaccination units and adult vaccination varieties. The total vaccination amount and vaccination rate were calculated. Results: By the end of 2022, there were 3 948 vaccination units providing adult vaccination in Shandong Province, with 0.36 adult vaccination clinics per 10 000 people. Adult vaccination including RabV(rabies vaccine for human use), InfV(influenza vaccine), HPV(human papillomavirus), HepB(hepatitis B vaccine), PPV23(23-valent pneumococcal polysaccharide vaccine), MenACYW135(meningococcal polysaccharide vaccine group ACYW135), MMR(measles, mumps and rubella combined attenuated live vaccine), HEV(hepatitise E vaccine), RZV(recombinant zoster vaccine), TV(tetanus vaccine) and HF(haemorrhagic fever with renal syndrome vaccine) vaccines were administered, with a cumulative dose of 40.056 9 million and an average of 0.1 doses per person per year from 2018 to 2022. The top three vaccines were RabV, InfV and HPV, accounting for 31.48%, 22.57%, and 15.93% of the total vaccination amount, respectively. The annual vaccination dose for adults increased from 3.477 3 million in 2018 to 13.308 6 million in 2022, with an average annual growth rate of 56.55%. The cumulative 5-year doses of RabV and TV were 15.90 doses per 100 people and 0.21 doses per 100 people. The average annual vaccination rate of InfV was 2.28%. The cumulative full vaccination rates of HPV, HepB, PPV23 and RZV were 12.44%, 1.61%, 0.52% and 0.17%, respectively. The cumulative 5-year doses of RabV and TV were 29.19 doses per 100 people and 0.43 doses per 100 people in the age group of 20 to<30 years old. The vaccination rates of InfV and PPV23 were 9.08% and 1.27% in the age group of 70 to<80 years old. The vaccination rate of RZV was 0.11% in the age group of 50 to<60 years old. The HPV vaccination rate was 18.09% in the age group of 20 to<30 years old, and the HepB, MenACYW135, MMR and HEV vaccination rates were 6.21%, 9.55%, 2.65%, and 2.83% in the 18-19 age group, respectively. Conclusion: There are relatively few types of adult vaccination in Shandong Province, with narrow coverage and low vaccination rates.
Adult ; Humans ; Young Adult ; Aged ; Middle Aged ; Adolescent ; Aged, 80 and over ; Papillomavirus Infections ; Vaccination ; Phenylbutyrates ; Influenza Vaccines