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.

Pulmonary fibrosis is a diffuse interstitial lung disease with poor prognosis,and its pathogenesis has not been fully clar-ified.Lipid,as a key component of cell structure involved in signal transduction,plays an important role in maintaining lung function.More and more studies show that lipid changes are closely related to the progress of pulmonary fibrosis.This paper briefly reviews the pulmonary fibrosis disease,the research pro-gress of lipidomics in pulmonary fibrosis and the role of various lipids in pulmonary fibrosis.

Aim To investigate the analgesic effect of ginsenoside Rd(GSRd)on spared nerve injury(SNI)induced neuropathic pain(NP)in mice and the under-lying mechanism.Methods SNI model was estab-lished and behavioral indexes were tested to verify the stability of the model and the analgesic effect of GSRd on neuralgia induced by SNI.The relationship between SNI-induced neuralgia and GABaergic nerve was ana-lyzed by GSRd in combination with gamma-aminobutyr-ic acid(GABA)system tool.Immunofluorescence staining was used to observe ventrolateral preoptic nu-cleus(VLPO)and ventrolateral periaqueductal gray in rats with neuralgia induced by SNI.The expression of c-Fos,c-Fos and GAT-1 immunopositive cells in VL-PAG and SDH were analyzed.The relationship be-tween the analgesic effect of GSRd and the nuclear group and nuclear group neurons of pain transduction pathway was analyzed.Results The pain threshold of SNI neuralgia mice began to change on the 3rd day af-ter operation,and pain sensitivity was produced,which lasted for at least 14 days.GSRd 500 or 1000 mg·kg-1 increased the pain threshold of SNI-induced neu-ralgia mice.GABA system tool drug could coordinate or antagonize the therapeutic effect of GSRd on neural-gia induced by SNI in mice.The c-Fos immunopositive cells of VLPO,VLPAG and SDH revealed a notable in-crease in SNI mice,and GSRd 500 mg·kg-1could re-duce the number of c-Fos and GAT-1 co-expressing im-munopositive cells in VLPO,VLPAG and SDH mice in-duced by SNI.Conclusions The neuralgia model in-duced by SNI is stable,and GSRd has significant anal-gesic effect.The mechanism involves down-regulating GAT-1 in VLPO,VLPAG and SDH to reduce its re-uptake of GABA in the synaptic gap,thereby enhancing the inhibitory effect of central GABaergic nerve.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

African swine fever virus(ASFV)I177L gene deletion vaccine is one of the key directions of African swine fever(ASF)live attenuated vaccine research and development.In order to effec-tively distinguish between the wild-type ASFV strain and the I177L gene-deleted strain,specific primers and probes were designed based on ASFV B646L and I177L genes,respectively.After screening and optimization,a duplex real-time PCR method was developed that can simultaneously detect these two genes.The results showed that ASFV B646L and I177L genes were detected spe-cifically and simultaneously by the method developed without cross-reactions with porcine circovir-us type 2,Seneca virus A,classical swine fever virus,foot-and-mouth disease virus,porcine respira-tory and reproductive syndrome virus.The detection limits of the duplex real-time PCR for recom-binant plasmids pUC57-B646L and pUC57-I177L were 1×103 copies/mL.The intra-and inter-as-say coefficients of variation were less than 4％,respectively.Detection of 122 pork and pork prod-ucts using the duplex real-time PCR developed and the real-time PCR recommended by WOAH showed that the coincidence rates of the two methods for B646L gene detection was 100％with two amplification curves appeared in the positive results of the established methods.The method established in this study can be used for the detection of ASFV I177L gene deletion strains,which provides technical support for ASF surveillance and epidemiological investigation.

AIM To observe the ameliorative effects of hesperidin on gentamicin-induced acute kidney injury(AKI)in mice,and to explore the correlation between the effects and inflammation and apoptosis.METHODS The mice were randomly divided into the normal group,the model group,the verapamil group(21.43 mg/kg)and the low and high dose hesperidin groups(100,200 mg/kg).With the AKI model established by intraperitoneal injection of gentamicin,the mice of each group underwent 14 days corresponding drug administration.After the intervention,the mice had their levels of 24-hour urine protein,renal index and renal function indexes detected;their levels of IL-10,IL-6 and TNF-α in serum and kidney tissue detected by ELISA;their renal pathological damage detected by HE staining;their renal apoptosis detected by TUNEL staining;their renal mRNA expressions of caspase-3,Bcl-2 and Bax detected by RT-qPCR;and their renal expressions of cleved caspase-3 and PI3K/Akt signaling pathway related proteins detected by Western blot.RESULTS Compared with the model group,the hesperidin groups displayed decreased levels of 24-hour urinary protein and renal index(P＜0.05);improved renal pathological damage in varying degrees;decreased levels of serum BUN,Scr and CysC(P＜0.05);increased IL-10 levels of serum and renal tissue(P＜0.05);decreased levels of IL-6 and TNF-α(P＜0.05);decreased renal apoptosis rate,caspase-3,Bax mRNA expressions and cleaved caspase-3 protein expression(P＜0.05);and increased expressions of Bcl-2 mRNA and PI3K/Akt proteins(P＜0.05).CONCLUSION Hesperidin can ameliorate gentamicin-induced AKI in mice,which is related to its anti-inflammatory efficacy and anti-apoptotic activity via PI3K/Akt signaling pathway.

Objective To investigate the development of follicles in polycystic ovary syndrome(PCOS)model rats treated with Xinjia Erjia Dihuang Tang and its possible mechanism.Methods Twenty-eight female SD rats with regular estrous cycle were selected and randomly divided into normal control group,model group,Chinese medicine group and Western medicine group,with 7 rats in each group.In addition to the normal control group,the other three groups were continuously given 0.1mg/(kg·d)of letrozole-carboxymethyl cellulose suspension to construct the PCOS rat model.Since the 22nd day,the traditional Chinese medicine group was given 5.268g/(kg·d)of Xinjia Erjia Dihuang Tang,the western medicine group was given 0.286mg/(kg·d)of ethinylestradiol cyproterone tablet,and the normal control group and model group were given 10ml/(kg·d)of distilled water.After 3 weeks,the ovarian coefficients of the rats in all groups were compared,and the morphological changes of the ovarian tissues of the rats in all groups were observed by hematoxylin-eosin staining.The serum hormones of the rats in all groups were detected by enzyme-linked immunosorbent assay,and the ovarian kisspeptin(Kp)and G-protein-coupled receptors(GPR54)protein expression levels were detected by Western blot.Results Compared with the normal control group,the follicles in the ovary of the model group showed more cystic dilatation and atresia,and the number of granular cell layers decreased,the ovarian coefficient of the model group was increased;Serum levels of testosterone(T),luteinizing hormone(LH)and Kp were increased in model group;Serum levels of follicle stimulating hormone(FSH)and estradiol(E2)and protein expressions of Kp and GPR54 in ovarian tissue of rats in the model group were significantly decreased(P<0.05).After treatment with Chinese medicine,compared with the model group,the number of follicles in the Chinese medicine group decreased,the layer number of granulosa cells increased,there were nearly mature follicles,and a small amount of corpus luteum existed,serum LH,T and Kp levels were decreased,serum FSH and E2 levels and ovarian Kp and GPR54 protein expressions were significantly increased(P<0.05).Conclusion The development of follicles in PCOS model rats was improved by the intervention of Xinjia Erjia Dihuang Tang.The therapeutic mechanism may be to affect the release of FSH and LH by regulating Kisspeptin/GPR54 system,so as to affect hormone content,adjust ovarian function,and improve follicle development and ovulation ability.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

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]