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 establish the method for content determination of three lignans of Dendrobium Fimbriatum Hook..Methods The lignans in Dendrobium tasselii were identified by high-performance liquid chromatography/multi-stage mass spectrometry(HPLC-ESI/MSn)coupled with ultraviolet absorption spectrometry(UV)coupled with retention time localization of high-performance liquid chromatography(HPLC).The separation was carried out on a Kromasil 100-5 C18 column(4.6 mm×250 mm,5 μm)using a gradient elution of acetonitrile-0.1%formic acid solution as the mobile phase,the volume flow rate was 0.8 mL·min-1 and the column temperature was 35℃,and the mass spectrometry was performed using an ESI ion source with the data collected in the negative ion mode.The HPLC content was determined on the same column as that of MS analysis,with the mobile phase methanol + acetonitrile(V/V=1∶1)-0.01 mol/L ammonium acetate solution,gradient elution,flow rate of 0.8 mL·min-1,column temperature of 40℃,and detection wavelength of 215 nm.Results Syringaresinol di-O-glucoside and(-)-Syringaresinol 4-O-β-D-glucopyranoside and DL-Syringaresinol were identified from Dendrobium fimbriatum Hook.,and the results of content determination showed that the linear ranges of above three components were respectively 0.1701-3.4020,0.1020-2.0400,0.0403-0.8060 μg(r≥0.9995),the average recoveries were in the range of 97.71%-101.67%,and the relative standard deviations(RSDs)were all less than 3.0%.The contents of Syringaresinol di-O-glucoside and(-)-Syringaresinol 4-O-β-D-glucopyranoside and DL-Syringaresinol in the 10 batches of samples were 0.7779-1.3852,0.0734-0.1966,0.0295-0.1882 mg·g-1.Conclusion This research method can provide a reference basis for the quality evaluation method of Dendrobium fimbriatum Hook..

Objective To compare the early predictive value of different scoring systems for the severity,organ failure and complications of acute pancreatitis(AP)in elderly patients under the newly revised Atlanta criteria.Methods Patients with acute pancreatitis treated was collected.After admission,complete the computed tomography severity index(CTSI),the bedside index of severity in acute pancreatitis(BISAP),the pancreatis 3(PANC-3)and the harmlessness acute pancreatitis score(HAPS).The area under receiver operating characteristic(ROC)curve(AUC),sensitivity,specificity and Yordan's index of four scores for predicting SAP,local pancreatic complications and multiple organ failure were compared.Results The areas under the ROC curve predicted by the CTSI,BISAP,PANC-3 and HAPS scoring systems for SAP were 0.76,0.91,0.48 and 0.55;sensitivities of 75.87％,89.61％,61.18％and 78.38％;specificity of 80.29％,74.72％,67.48％and 69.69％;Yordan's index of 0.56,0.64,0.29 and 0.48,respectively.The AUC of CTSI,BISAP,PANC-3 and HAPS scoring systems for predicting local pancreatic complications were 0.94,0.82,0.59 and 0.64;sensitivity of 74.59％,68.23％,71.11％and 69.28％;specificity of 93.88％,83.01％,78.59％and 76.46％;Yordan's index were 0.68,0.51,0.50 and 0.46,respectively.The AUC of CTSI,BISAP,PANC-3 and HAPS scoring systems for predicting multiple organ failure were 0.60,0.84,0.64 and 0.80,sensitivities were 54.18％,74.82％,58.59％and 65.67％,specificity were 76.11％,77.20％,72.68％and 89.36％,Jordan's indices were 0.30,0.52,0.31 and 0.55,respectively.Conclusion BISAP score is higher than CTSI,HAPS and PANC-3 scoring system in predicting the accuracy of sap and the risk of multiple organ failure.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Objective To investigate the expression of m6 A methyltransferase-like protein 14(METTL14)in the hippocampus of depression-like mice,and to provide a theoretical basis for further study of the molecular mecha-nism of depression and new drug targets.Methods 1)Twenty-four male C57BL/6J mice were divided into con-trol group and depression model group.The control group was fed normally,and the model group was kept in single animal cage for 4 months and added with Chronic Unpredictable Animal Stress(CUMS)to establish the depression-like model.2)After modeling,depression-like behaviors in model group were tested using forced swimming test(FST),sucrose preference test(SPT)and tail suspension test(TST).3)Twenty-four hours after completion of behavioral test,the hippocampus tissues of mice were collected,and the expression of m6 A methyltransferase-like protein METTL14 in the hippocampus of mice was detected by molecular biology experiments.Results 1)The mice in the model group showed significant depression-like behavior;2)The expression of MET-TL14 in the hippocampus of the model group showed an increased mRNA expression with the increased m6 A modifi-cation.3)In the model group,the expression of METTL14 in hippocampal CA1,CA3 and DG districts increased and there was neuronal damage found.Conclusions m6 A methylation function has been proved to be more active in the hippocampus of depressed mice.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

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.

This study was aimed at creating an engineered strain of Bacillus subtilis for efficient expression of biologically active type 2 toxin B(TcdB2)derived from a highly virulent strain of Clostridium difficile.The TcdB2 gene was cloned from ST1/RT027 strain genome DNA,incorporated into the PHT01 vector,and then transformed into B.subtilis strain WB800N for prokaryotic expression.Cell toxicity assays revealed that the recombinant TcdB2 exhibited cytotoxic effects in various cells.The engineered B.subtilis strain effectively expressed biologically active TcdB2,thus providing a basis for further exploration of the pathogenic mechanisms of highly virulent strains of C.difficile and establishing a foundation for potential vaccine can-didate targets.