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 study the effect of Hedysarum polysaccharides(HPS)on the farnisol X receptor(FXR)-small heterodimer chaperone(SHP)-sterol regulatory element-binding protein 1 c(SREBP-1c)signaling pathway in the non-alcoholic fatty liver disease cell model.Methods The cells were cultured with 1.2 mmol·L-1 fatty acids to construct the non-alcoholic fatty liver disease cell model.The cell were divided into normal group(complete medium),model group(1.2 mmol·L-1 fatty acid solution),positive control group(1.2 mmol·L-1 fatty acid solution+50 μmol·L-1 alpha-lipoic acid)and experimental group(1.2 mmol·L-1 fatty acid solution+80 mg·L-1 HPS),culture for 24 h.The content of triglyceride(TG)and total cholesterol(TC),the activity of glutamate transaminase(GOT)and glutamate transaminasewas(GPT)detected by GPO-PAP enzyme method;the apoptosis rate was detected by flow cytometry;the expressions of FXR,SHP,SREBP-1c protein and mRNA in hepatocytes were detected by Western blot and reverse transcription-polymerase chain reaction(RT-PCR).Results The contents of TG in hepatocytes of normal group,model group,positve control group and experimental group were(2.91±1.13),(6.81±1.32),(3.72±0.52)and(4.67±0.62)mmol·gprot-1;the contents of TC in these four groups were(23.66±4.92),(67.96±5.56),(29.41±4.22)and(54.34±3.96)mmol·gprot-1;the activity of GOT in these four groups were(249.10±11.59),(322.63±28.81),(288.89±19.14)and(266.91±8.77)U·gprot-1;the activity of GPT in these four groups were(58.83±16.88),(134.55±22.96),(89.63±15.81)and(77.37±7.25)U·gprot-1,respectively;FXR mRNA expression levels were 1.01±0.16,2.09±0.12,1.83±0.17 and 1.45±0.15,respectively;SHP mRNA expression levels were 1.00±0.11,0.51±0.15,0.64±0.14 and 0.70±0.14,respectively;SREBP-1c mRNA were 1.00±0.08,1.57±0.19,1.37±0.13 and 1.21±0.15;the expression levels of FXR protein were 1.00±0.02,1.63±0.03,1.42±0.02 and 1.25±0.03,respectively;the expression levels of SHP protein were 1.00±0.02,0.23±0.01,0.54±0.21 and 0.62±0.02;the expression levels of SREBP-1c protein were 1.00±0.03,4.08±0.05,1.99±0.02 and 1.48±0.01,respectively.Compared with the normal group,there were significant differences in the above indexes of model group(all P＜0.05);compared with the model group,there were significant differences in the above indexes of experimental group(all P＜0.05).Conclusion HPS may protect liver cells by regulating the FXR-SHP-SREBP-1 c signaling pathway,reducing lipid synthesis in liver cells.

Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.

Objective To observe the clinical efficacy and safety of rituximab injection combined with leflunomide tablets in the treatment of patients with systemic lupus erythematosus(SLE).Methods The SLE patients were divided into control and treatment groups according to cohort method.The control group received leflunomide with 50 mg·d-1 after meal in the first 3 days of treatment and was adjusted to 20 mg·d-1 thereafter.On the basis of control group,the treatment group was combined with rituximab,375 mg·m-2 was given intravenously every 2 weeks in the first 3 times of treatment,and adjusted to once every 4 weeks from the 4th dose.Two groups were treated for 24 weeks.The clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores,serological indicators,24-hour urinary protein and adverse drug reactions were compared between two groups.Results The treatment and control groups were enrolled 74 cases and 72 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.89％(68 cases/74 cases)and 79.17％(57 cases/72 cases)with significant difference(P＜0.05).After treatment,the SLEDAI scores of treatment and control groups were(7.21±1.67)and(9.03±1.35)points;the levels of anti-Smith/ribonucleoprotein antibodies were(81.43±18.25)and(59.38±14.61)U·mL-1;the levels of immunoglobulin G were(12.04±2.15)and(17.28±2.64)g·L-1;the levels of interleukin-10 were(33.39±7.13)and(39.87±9.02)pg·mL-1;24-hour urinary protein quantification were(1.46±0.32)and(2.67±0.54)g·24 h-1;all the differences were statistically significant(all P＜0.05).The drug adverse reactions of two groups were liver and kidney function injury and digestive tract reactions.The total incidences of drug adverse reactions in the treatment and control groups were 13.51％and 5.56％without significant difference(P＞0.05).Conclusion Rituximab injection combined with leflunomide tablets has a definitive clinical efficacy in the treatment of SLE patients,which can significantly reduce disease activity and inflammatory reactions,improve immune function,without increasing the incidence of drug adverse reactions.

Objective To study the effect of Hedysarum polysaccharides(HPS)on the expression of transforming growth factor-β,(TGF-β1),smad homologue 3 recombinant protein(smad3)and smad7 in renal tissue of db/db mice with diabetic nephropathy(DN).Methods According to their body weight,6-week-old male db/db mice were randomly divided into 5 groups:model group(0.9％NaCl 0.2 mL·d-1),positive control group(22.75 mg·kg-1·d-1 irbesartan)and experimental-H,-M,-L groups(200,100,50 mg kg-1·d-1 HPS),with 10 mice in each group;another 10 SPF grade male C57BL/6 mice of the same week were selected as normal group(0.9％NaCl 0.2mL·d-1).The mice in the 6 groups were given intragastric administration once a day for 12 weeks.The blood glucose concentration of mice was measured before treatment and at the 4th,8th and 12th week after treatment.The expression levels of TGF-β1,smad3 and smad7 were detected by Western blotting.Results After treatment,the blood glucose levels of the model group was significantly higher than those of the normal group(all P＜0.01);compared with the model group,the levels of blood glucose in the experimental-H,-M groups decreased significantly,and the differences were statistically significant(P＜0.05,P＜0.01).The relative expression levels of TGF-β,protein in normal group,model group,positive control group and experimental-H,-M groups were 0.71±0.16,1.66±0.18,1.00±0.17,0.88±0.15 and 1.23±0.15;the relative expression levels of smad3 protein were 0.89±0.32,2.26±0.35,1.24±0.31,1.05±0.30 and 1.67±0.35;the relative expression levels of smad7 protein were 1.66±0.03,0.60±0.03,1.10±0.07,1.48±0.08 and 0.97±0.09;there were statistically significant differences between the experimental-H,-M groups and the model group(P＜0.05,P＜0.01).Conclusion Hedysarum polysaccharides can improve renal fibrosis and delay the development of diabetic nephropathy by regulating the level of blood glucose,inhibiting TGF-β1,smad3 and increasing the expression of smad7.

Objective To evaluate the bioequivalence and safety of two pyrazinamide tablets in healthy Chinese subjects.Methods An open,randomized,single-dose,two-sequence,two-cycle,double-cross trial design was used.All 48 healthy subjects(24 in fasting and 24 in fed trial)were randomized to receive a single oral dose of a 0.5 g pyrazinamide tablet(test or reference)per cycle.The plasma concentration of the drug was determined by liquid chromatography coupled to tandem mass spectrometry method.The pharmacokinetic parameters were calculated by WinNonlin v8.2,and the bioequivalence was evaluated by SAS 9.4.Results In the fasting group,the Cmax of the test and reference preparation of pyrazinamide tablets were(13.28±2.82)and(12.88±4.49)μg·mL-1,the AUC0-t were(139.17±26.58)and(138.63±28.92)h·μg·mL-1,the AUC0-∞ were(148.96±33.65)and(148.71±36.97)h·μg·mL-1 respectively.In the fed group,the Cmax of the test and reference preparation of pyrazinamide tablets were(11.89±1.96)and(11.99±1.92)μg·mL-1,the AUC0-t were(138.22±37.21)and(141.68±25.80)h·μg·mL-1,the AUC0-∞ were(152.20±32.41)and(151.04±28.05)h·μg·mL-,respectively.The 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ geometric mean ratios of the test and reference preparation were all within 80.00％to 125.00％.The incidence of adverse events was 16.70％for both the test and reference preparation in the fasting group and 8.30％for both the test and reference preparation in the fed group,all of which were mild in severity.Conclusion The test and reference preparation of pyrazinamide tablets were bioequivalent,safe and well tolerated in healthy Chinese subjects under fasting and fed conditions.

Over the years of exploration and development, the surgical techniques and prognosis of liver transplantation in China have been significantly improved, resulting in a notable decrease in the prevalence of postoperative complications. However, ischemic-type biliary lesion remain a non-negligible issue. The Third Affiliated Hospital of Sun Yat-sen University formulated and published the "Expert Consensus on the Diagnosis and Treatment of Ischemic-Type Biliary Lesions after Liver Transplantation in Mainland China" in 2015, which has now been updated into a guideline based on current conditions and literature reports. This guideline elaborates in detail on the definition, incidence, pathogenesis, diagnosis, prevention of high-risk factors, and treatment of ischemic-type biliary lesion, aiming to provide standardized and normative guidance for the diagnosis and treatment of ischemic-type biliary lesion after liver transplantation, thereby reducing the rate of re-transplantation and fatality, and to improve the overall quality of life of liver transplant recipients.

Iron is an essential element for living organisms that plays critical roles in the process of bacterial growth and metabolism. However, it remains to be elucidated whether piuB encoding iron-uptake factor is involved in iron uptake and pathogenicity of Xanthomonas axonopodis pv. glycines (Xag). To investigate the function of piuB, we firstly generated a piuB deletion mutant (ΔpiuB) by homologous recombination. Compared with the wild-type, the piuB mutant exhibited significantly reduced growth and virulence in host soybean. The mutant displayed markedly increased siderophore secretory volume, and its sensitivity to Fe³⁺, Cu²⁺, Zn²⁺ and Mn²⁺ was significantly enhanced. Additionally, the H₂O₂ resistance, exopolysaccharide yield, biofilm formation, and cell mobility of ΔpiuB were significantly diminished compared to that of the wild-type. The addition of exogenous Fe³⁺ cannot effectively restore the above characteristics of ΔpiuB. However, expressing piuB in trans rescued the properties lost by ΔpiuB to the levels in the wild-type. Taken together, our results demonstrated that PiuB is a potential factor for Xag to assimilate Fe³⁺, and is necessary for Xag to be pathogenic in host soybean.
Iron ; Glycine max ; Virulence ; Xanthomonas axonopodis/genetics* ; Hydrogen Peroxide

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae. Guanxinning Tablet (GXNT), which is composed of Salvia miltiorrhiza and Ligusticum Chuanxiong, has significant antithrombotic activity, but the similarities and differences between its anti-conventional thrombus and microthrombus induced by COVID-19 remain unclear. In this paper, the main active components, potential targets and mechanisms of GXNT in the treatment of thrombus and microthrombus caused by COVID-19 were preliminarily revealed by using anti-platelet experiments in vitro, network pharmacology analysis, molecular docking technology and molecular biology experiments. The results of platelet aggregation and adhesion experiments in vitro showed that GXNT had significant anti-platelet aggregation and adhesion activities in a dose-dependent manner. Using network pharmacology analysis, it was revealed that salvianolic acid B, tanshinone IIA, caffeic acid and ligustrazine in GXNT could resist thrombus and microthrombus caused by COVID-19 through key targets as the high mobility group box 1 protein (HMGB1), tumor necrosis factor (TNF), interleukin 6 (IL6) and AKT serine/threonine kinase 1 (AKT1). HMGB1 signaling pathway is one of its key common mechanisms. Western blot also indicated that GXNT significantly inhibited the expression of HMGB1 protein in platelets. In summary, this paper explores the similarities and differences between the mechanism of GXNT against conventional thrombus and microthrombus caused by COVID-19 and provides drug reference and theoretical basis for clinical prevention and treatment of long COVID sequelae. The animal experiment has been approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2023187g1549).