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 investigate the effects of autologous platelet-rich plasma (aPRP) collected using a continuous blood cell separator on blood conservation and prognosis in patients with type A aortic dissection. Methods: The clinical data of patients who underwent emergency aortic replacement for acute type A aortic dissection at our hospital from January 2020 to December 2023 were respectively analyzed. Patients were divided into two groups based on whether they received aPRP collection before surgery for subsequent reinfusion: the aPRP group (n=32) and the control group (n=35). The volume of aPRP collected and the platelet concentration in the aPRP were recorded. The volumes of allogeneic blood and blood products transfused, and the associated costs during hospitalization were compared between two groups. Intraoperative blood loss, perioperative laboratory parameter changes, 24-hour postoperative drainage volume, duration of ICU stay and mechanical ventilation, length of hospital stay, and mortality rate of the two groups were also compared. Results: The platelet concentration in aPRP was (491.5±85.4)×10 /L, accounting for (24.1±9.6)% of the patient's total platelet count. The volume of aPRP collected accounted for (23.0±6.3)% of the patient's total plasma volume. Compared with the control group, the aPRP group demonstrated significantly reduced transfusion volumes of allogeneic red blood cells, plasma, and platelets (P<0.05), along with significantly lower blood-related costs during hospitalization (P<0.05). Postoperative coagulation parameters (APTT, PT, INR, and TEG) were significantly improved (P<0.05), and platelet counts were markedly increased (P<0.05) in aPRP group as compared with the control group. No statistically significant differences were observed in postoperative use of prothrombin complex concentrate and fibrinogen between the two groups. Similarly, there were no significant differences in postoperative 24-hour drainage volume, 24-hour extubation rate, ICU length of stay, duration of mechanical ventilation, or total hospital length of stay. The incidence of complications and mortality did not differ significantly between the two groups. Conclusion: The administration of aPRP significantly reduces the requirement for perioperative allogeneic blood transfusion in patients undergoing surgery for type A aortic dissection. Furthermore, it enhances coagulation function and reduces associated transfusion costs, thereby establishing itself as an effective and safe strategy for blood conservation.

Objective To understand the epidemiological characteristics of scrub typhus disease and to provide a scientific basis for the prevention and control of scrub typhus disease. Methods Descriptive epidemiological methods were used to analyze the population and regional distribution of scrub typhus. Seasonal characteristics were analyzed using concentration method and circular distribution method, and incidence trend was analyzed using joinpoint regression model. Results The annual incidence rate of scrub typhus was 0.95/100 000 from 2010 to 2022. The incidence rate of male was 0.77/100 000, lower than that of female 1.12/100 000 (χ²=18.89, P<0.05). The incidence rate of the 60-74 years old group was 3.38/100,000, and the total number of cases in the age group 45-74 years was 416 (74.95%). Occupational distribution was mainly among farmers, with 448 cases (80.72%). The top three regions with the highest number of reported cases (in order: Donghai County, Ganyu District, and Guannan County) reported a total of 416 cases, accounting for 74.95%. Concentration ratio was M=0.9408, and the incidence of scrub typhus disease was strictly seasonal. Circular distribution results showed a^-=-62.3728, S=20.8960. The circular distribution results indicated that the peak day was October 19th, and the peak period was between October 7 to December 19. The average annual percentage change (AAPC) of the incidence rate from 2010 to 2022 was 13.70%, 95% CI (-8.62%~41.48%), and the incidence rate showed an upward trend (t=1.15, P=0.249). Conclusion The incidence of scrub typhus disease is strictly seasonal, and the incidence rate over the years shows an upward trend. It is necessary to strengthen monitoring and take various intervention measures to reduce the risk of scrub typhus disease.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Objective To retrospectively analyze the ultra-fast track anesthesia(UFTA)methods and perioperative anesthesia management experiences of transcatheter mitral valve edge-to-edge repair(TEER)in the treatment of functional mitral regurgitant.Methods In this retrospective study,patients underwent the TEER procedure and received UFTA in Fuwai Yunnan Hospital,from May 2022 to September 2022 for heart failure combined with moderate to severe or severe functional mitral regurgitant were included.Baseline,preoperative complications,cardial function and anesthesia classification,amino-terminal probrain natriuretic peptide(NT-proBNP),ultrasound examination results,surgery time,extubation time,intraoperative anesthetic and vasoactive drug,complications related to TEER and UFTA,perioperative,and postoperative 30-day and one-year follow-up data were collected.All perioperative clinical data were recorded and analyzed.Results A total of 30 patients were enrolled,11 patients(36.7％)were female,mean age was(63.6±6.1)years,NYHA classification IV 14 patients(46.7％),left ventricular ejection fraction(LVEF)(36.0±8.1)％,the end-diastolic volume of the left ventricle(66.0±8.2)mm,mitral regurgitation 4+14 patients(56.7％),3+17 patients(43.3％),NT-proBNP(1 934.1±1 973.5)pg/ml,1 patient(3.3％)used high-dose vasoactive drugs during surgery.All patients did not experience nausea,vomiting,delirium,respiratory depression,perioperative transesophageal echocardiography-related gastrointestinal bleeding,pericardial effusion,cerebrovascular accidents,emergency surgery or secondary intervention,or other serious adverse events within 24 hours after surgery.No 30-day all-cause death occurred;the mean postoperative hospital stay was(7.4±2.8)days.All patients completed one-year follow-up,LVEF(37.6±11.1)％,the end-diastolic volume of the left ventricle(63.2±8.6)mm,mitral regurgitation 2+7 patients(23.3％),1+23 patients(76.7％),NT-proBNP(1 949.2±2 576.6)pg/ml.Conclusions Ultra-fast track anesthesia can be safely applied to TEER in treating functional mitral regurgitant patients.

Diabetes mellitus is a metabolic disease with high incidence and many complications,among which type 2 diabetes mellitus(T2DM)accounts for a large proportion.Current studies have shown that T2DM is accompanied by damage of liver,kidney,and other organs and its complications seriously en-danger human health.Ferroptosis generates many Reactive Oxygen Species(ROS)through the Fenton reaction,and the accumulation of ROS activates Hypoxia Inducible Factor-1(HIF-1α).As a result,the level of vascular endothelial growth factor(VEGF)is increased.Ferrostatin-1(Fer-1),a ferroptosis in-hibitor,has strong antioxidant capacity.Therefore,based on the hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)signaling pathway,we explored the therapeutic effect of Fer-1 on the liver and kidney tissues of diabetic mice.db/db mice(21～22 weeks old)were used as the model of diabetes mellitus.Ferroptosis inhibitor Fer-1 was used as the intervention drug.db/m mice served as the blank control group,and body weight and blood glucose were measured for 4 weeks.Food intake and water intake were recorded in each group.The levels of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in the serum were measured.ROS and Glutathione(GSH)activity in liver and kidney tissues and urinary protein content were measured.Liver and kidney tissue sections were stained with Hematoxylin-Eosin(HE),and the pathological morphology was observed under a light microscope.The protein levels of HIF-1α,VEGF,and glutathione peroxidase 4(GPX4)in liver and kidney tissues were detected by Western blot.In db/db mice,Fer-1(1 mg·kg-1,ig)could significantly reduce the a-mount of food and water intake,the levels of ALT and AST in serum,the ROS production in liver and kidney tissues,and the level of urine protein,but significantly increase the activity of GSH,thus improve the pathological conditions of liver and kidney.Fer-1 also significantly inhibited HIF-1α and VEGF pro-tein indexes and increased GPX4 protein levels in liver and kidney tissues.Although Fer-1 can not change the body weight and reduce blood glucose in diabetic mice,it can play a therapeutic role in the liver and kidney tissues of diabetic mice in the middle and late stages,and its mechanism may be related to HIF-1α/VEGF and GPX4.

Objective:To evaluate the safety and efficiency of robotic visualization system(RVS)-assisted microsurgical re-construction of the reproductive tract in male rats and the satisfaction of the surgeons.Methods:We randomly divided 8 adult male SD rats into an experimental and a control group,the former treated by RVS-assisted microsurgical vasoepididymostomy(VE)or vaso-vasostomy(VV),and the latter by VE or VV under the standard operating microscope(SOM).We compared the operation time,me-chanical patency and anastomosis leakage immediately after surgery,and the surgeons'satisfaction between the two groups.Results:No statistically significant difference was observed the operation time between the experimental and the control groups,and no anasto-mosis leakage occurred after VV in either group.The rate of mechanical patency immediately after surgery was 100％in both groups,and that of anastomosis leakage after VE was 16.7％in the experimental group and 14.3％in the control.Compared with the control group,the experimental group achieved dramatically higher scores on visual comfort(3.00±0.76 vs 4.00±0.53,P＜0.05),neck/back comfort(2.75±1.16 vs 4.38±1.06,P＜0.01)and man-machine interaction(3.88±1.55 va 4.88±0.35,P＜0.05).There were no statistically significant differences in the scores on image definition and operating room suitability between the two groups.Conclusion:RVS can be used in microsurgical reconstruction of the reproductive tract in male rats and,with its advantages over SOM in ergonomic design and image definition,has a potential application value in male reproductive system micosurgery.

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.
Animals ; Mice ; Colitis, Ulcerative/drug therapy* ; Ursodeoxycholic Acid/adverse effects* ; Berberine/pharmacology* ; Interleukin-6 ; Tumor Necrosis Factor-alpha/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Colon ; Nanoparticles ; Dextran Sulfate/adverse effects* ; Disease Models, Animal ; Colitis/chemically induced*

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 μg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.