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.

ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

Child ; Humans ; Granulomatous Disease, Chronic/complications* ; Pneumonia

Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.

Objective To generate minichromosome maintenance protein 2(MCM2)gene knockout cervi-cal cancer HeLa cell lines using inducible CRISPR/Cas9 technology,and to explore the effect of MCM2 on DNA replication and replication stress.Methods The inducible CRISPR/Cas9 system,TLCV2,was used to construct MCM2 knockout HeLa cell lines.And the cell lines were divided into control group(Control),knockout group 1(KO1),and knockout group 2(KO2).Western blot,Edu incorporation experiment,real-time quantitative PCR(qPCR),immunofluorescence and MTT assay were used to analyze the effects of MCM2 knockout on DNA replica-tion and replication stress induced by hydroxyurea.Results The CRISPR/Cas9 system successfully knocked out the MCM2 gene after induction,and MCM2 knockout affected the stability of MCM2-7 complex.Compared with the control cells,MCM2 knockout cells had a dramatic decrease in the capacity of DNA replication,and the mRNA levels of Cyclin A1,Cyclin E1 and CDK4.Under DNA replication stress,MCM2 knockout cells decreased cell viability,DNA damage repair capacity,and increased genomic instability compared with control cells.Conclusion Knockout of MCM2 gene reduces the DNA replication capacity of HeLa cells under normal conditions and cell viability under replication stress.This study successfully generates MCM2 gene inducible knockout HeLa cell lines,laying the foundation for further research on the role and biological function of MCM2 gene in the occurrence and progression of cervical cancer.

Background Affected by concentration, composition, and population tolerance of air pollutants, the relationship between air pollutants and population health has regional differences. There is still a research gap in Guiyang. Objective To explore the short-term effects of air pollutant concentrations in low-pollution areas on the outpatient volume of respiratory diseases. Methods Spearman correlation analysis was used to evaluate the correlation between air pollutants, meteorological factors, and respiratory outpatient volume from January 1, 2013 to December 31, 2020 in Guiyang City. A single pollutant distribution lag nonlinear model and a multi-pollutant interaction model were established based on Poisson distribution. A three-dimensional diagram was drawn to display the relationship between air pollutants and respiratory outpatient volume. Quantitative analysis was conducted on the attribution risk and lag effect of air pollutant concentration on outpatient volume of respiratory diseases in Guiyang City. Results The results of the single pollutant model showed that fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), carbon monoxide (CO), and sulfur dioxide (SO₂) elevated the outpatient volume of respiratory diseases. The maximum relative risk (RR) and 95%CI values of PM_2.5, NO₂,CO, and SO₂ appeared on Day 2, 0, 5, and 6, respectively, which were 1.019 (1.015, 1.023), 1.146 (1.122, 1.171), 1.129 (1.116, 1.143), and 1.046(1.040, 1.052), respectively. For every quartile concentration increment of PM_2.5, NO₂, CO, or SO₂, the outpatient volume of respiratory diseases increased by 0.943% (0.111%, 1.782%), 4.050% (3.573%, 4.529%), 0.595% (0.317%, 0.874%), or 0.667% (0.235%, 1.100%), respectively. The maximum RR (95%CI) of O₃ was 1.015 (1.007, 1.023) and appeared on Day 0. The results of multi-pollutant model showed that PM_2.5, NO₂, CO, SO₂, and O₃ all elevated the outpatient volume of respiratory diseases. The maximum RR values of PM_2.5, NO₂, CO, SO₂ and O₃ appeared on Day 14, 0, 5, 7 and 0, respectively, which were 1.027 (1.021, 1.034), 1.213 (1.179, 1.248), 1.059 (1.043, 1.074), 1.016 (1.005, 1.026), and 1.024 (1.015, 1.033), respectively. Compared with the single pollutant model, the RR values of PM_2.5, NO₂, and O₃ on the outpatient volume of respiratory diseases in the multi-pollutant model showed an upward trend, while the RR values of CO and SO₂ in the multi-pollutant model showed a downward trend. Conclusion The impact of low concentrations of PM_2.5, NO₂, CO, and SO₂ on human health cannot be ignored.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

The standardized workflow of computer-aided static guided implant surgery includes preoperative exami-nation,data acquisition,guide design,guide fabrication and surgery.Errors may occur at each step,leading to irrevers-ible cumulative effects and thus impacting the accuracy of implant placement.However,clinicians tend to focus on fac-tors causing errors in surgical operations,ignoring the possibility of irreversible errors in nonstandard guided surgery.Based on the clinical practice of domestic experts and research progress at home and abroad,this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection,data collection,guide de-signing and manufacturing and describes strategies to resolve errors so as to gain expert consensus.Consensus recom-mendation:1.Preoperative considerations:the appropriate implant guide type should be selected according to the pa-tient's oral condition before surgery,and a retaining screw-assisted support guide should be selected if necessary.2.Da-ta acquisition should be standardized as much as possible,including beam CT and extraoral scanning.CBCT performed with the patient's head fixed and with a small field of view is recommended.For patients with metal prostheses inside the mouth,a registration marker guide should be used,and the ambient temperature and light of the external oral scan-ner should be reasonably controlled.3.Optimization of computer-aided design:it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers.Properly designing the retaining screws,extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors.4.Improving computer-aided production:it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postpro-cessing procedures.

Objective To analyze the TCM syndrome and treatment rule for the treatment of chronic atrophic gastritis based on data mining;To provide reference for its clinical treatment.Methods With the help of the big data platform of evidence-based literature of TCM covering several dominant diseases in the field of digestion,literature on the experience of famous doctors,theoretical discussion and case reports in the treatment of chronic atrophic gastritis published from 1 January 2000 to 31 July 2022 was retrieved.Medical records were screened according to the inclusion and exclusion criteria.The data of TCM disease names,clinical symptoms,tongue manifestation,pulse manifestation,TCM syndrome,TCM treatment method and other terms in medical records were standardized and statistically analyzed.Results Totally 169 articles were included,including 228 medical cases,involving 228 patients,with a cumulative number of 361 visits,with an average age of(53.17±11.11)years old,with the largest number of 50-60 years old.Chronic atrophic gastritis mostly belonged to the categories of"stomach pain"and"epigastric puffiness"in TCM,and its main symptoms were stomach pain,epigastric puffiness and belching.The common tongue manifestation include dark red tongue,white moss,thin or greasy moss.The common pulse manifestation included wiry slippery pulse,wiry thready pulse and wiry pulse.The high-frequency syndromes included liver-stomach qi stagnation syndrome,spleen-stomach dampness-heat syndrome,liver-qi stagnation and spleen-qi deficiency syndrome.The disease locations were mainly in the stomach,spleen and liver,and the syndrome elements were mainly qi deficiency,qi stagnation,blood stasis,dampness and heat,etc.The complex syndrome elements were more than the single syndrome elements,and the two syndrome elements of qi deficiency + qi stagnation was the most common.The most commonly used treatment methods were supplementing,regulating qi and regulating blood.Conclusion The treatment of chronic atrophic gastritis with TCM mostly focuses on the stomach,spleen and liver.The core syndrome elements are qi deficiency,qi stagnation,and blood stasis.The methods of nourishing qi and strengthening the spleen,soothing the liver and stomach,regulating qi and blood are often used.

Objective:To investigate the clinical characteristics, muscle pathological features and treatment in patients with Juvenile idiopathic inflammatory myopathy (JIIM) with positive anti-nuclear matrix protein 2 (NXP2) antibody.Methods:The clinical data of 8 IMM patients with positive anti-NXP2 antibody were collected and the clinical manifestations, auxiliary examinations, muscle pathological changes and therapeutic effects were retrospectively analyzed.Results:The ratio of male to female was 1:3. The median age of disease onset was (6.1±3.8) years. Eight cases had proximal muscle weakness, 7 had dermatomyositis-like rash, 5 had myalgia,4 had calcinosis,3 had skin ulcer, 2 had edema and 1 had abdominal pain. Five cases had elevated serum creatine kinase. Eight cases with lower limb muscle MRI showed abnormal signals in muscle, space between muscles and fat tissue, 3 cases with chest high-resolution CT (HRCT) showed interstitial lung disease. Abdominal CT of 1 case showed irregular thickening, edema and peripheral inflammatory exudation in ascending colon and proximal transverse colon. Pathological biopsy of skeletal muscle showed perifascicular atrophy, inflammatory cell infiltration in fascicular membrane and around small vessels and muscle fiber space. Edema, hyperplasia could be seen in interstitium; but dissolved necrosis, and regenerated muscle fibers were rarely seen. Treatments included glucocorticoids, immunosuppressive agents and biological agents (1 case). After 6 months of follow-up, 5 cases had good outcomes and 3 cases had poor outcomes.Conclusion:Dermatomyositis is the major clinical manifestation of idiopathic inflammatory myopathy with positive anti-NXP2 antibody.It is associated with myasthenia, calcinosis, skin ulcers and intestinal vasculitis. The pathological changes in skeletal muscle are relatively slightmild. Glucocorticoids combined with immunosuppressive agents are effective in most cases.