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.

Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Aim To observe the effect of Astragalus membranaceus and Angelica sinensis on the apoptosis of chondrocytes,and to investigate the effect of Astrag-alus membranaceus and Angelica sinensis on the sur-vival of fresh ostecartilage allograft.Methods Forty-eight 4-month-old New Zealand white rabbits,half male and half female,were randomly divided into sham operation group,model group,positive group and As-tragalus and Angelica 5∶1 group.In addition to the sham operation group,the other groups were both male and female donors and recipients for knee joint osteo-cartilage cross transplantation modeling.After 8 weeks of drug intervention,samples were taken for general observation,HE staining,saffrane-O staining,immu-nohistochemical staining,qPCR and Western blot de-tection.Results Compared with model group,As-tragalus and Angelica 5∶1 group and positive group,the repair site healed better,the morphology of osteo-chondrocytes tended to be normal,and the division and proliferation were obvious.Proteoglycan deposition in-creased and type Ⅱ collagen content was higher,the differences were statistically significant(P＜0.05).qPCR and Western blot results showed that compared with model group,the mRNA and protein expressions of Bax,caspase-3 and caspase-9 in other groups were significantly decreased(P＜0.05).Conclusion As-tragalus and Angelica can promote the survival of fresh osteochondral allograft,and its mechanism may be re-lated to promoting collagen production,promoting chondrocyte proliferation and inhibiting chondrocyte apoptosis.

Objective To compare early clinical and imaging results of domestic HURWA and imported Brainlab Knee3 surgical robot-assisted knee replacement.Methods A retrospective analysis was performed on 93 patients with knee os-teoarthritis(KOA)who underwent robot-assisted descending total knee arthroplasty(TKA)from January 2021 to July 2023,and they were divided into BRATKA group and HRATKA group according to use of robotic system.There were 40 patients in BRATKA group,including 16 males and 24 females,aged from 55 to 90 years old with an average of(64.3±7.0)years old;27 patients with grade Ⅲ and 13 patients with grade Ⅳ according to Kellgren-Lawrence(K-L);18 patients on the right side and 22 patients on the left side;the courses of disease ranged from 1 to 30 years with an average of(15.3±7.6)years;imported Brainlab Knee3 surgical robot assisted system was adopted.There were 53 patients in HRATKA group,including 18 males and 35 females,aged from 52 to 81 years old with an average of(64.4±8.5)years old;30 patients with grade Ⅲ and 23 patients with grade Ⅳ;21 patients on the right side and 32 patients on the left side;the courses of disease ranged from 1 to 32 years with an average of(16.4±7.9)years;HURWA surgical robot assisted system was adopted.Operation time,perioperative total blood loss,incision length and postoperative complications were compared between two groups.Deviation angle of hip-knee-an-kle angle(HKAA)before operation and on the first day after operation was compared between two groups.Later tibal compo-nent(LTC),frontal femoral component(FFC),later femoral component(LFC)and frontal tibal component(FTC)at 1 day af-ter on the first day after operation was compared between two groups.Knee Society score(KSS),visual analogue scale(VAS)and range of motion(ROM)of knee joint were compared between two groups before operation and on the 3rd and 90th day af-ter operation.Results Both groups were followed up for 11 to 18 months with an average of(14.4±2.1)months,and the wounds of all patients healed well.Operation time and incision length of BRATKA group were(132.1±34.6)min and(12.9±1.9)cm,while(94.1±10.8)min and(14.8±2.1)cm in HRATKA group,respectively,and the differences between two groups were statistically significant(P＜0.05).There were no significant difference in perioperative total blood loss and preoperative deviation angle of HKAA between two groups(P＞0.05).Deviation angle of HKAA,FFC angle and LFC angle in BRATKA group were(1.90±0.91)°,(87.90±1.51)°and(9.00±3.2)°,respectively;while(0.93±1.04)°,(89.03±0.96)° and(7.63±0.59)° in HRATKA group,respectively,and the differences between two groups were statistically significant(P＜0.05).There were no significant dif-ferences in FTC and LTC between two groups(P＞0.05).There were no significant differences in VAS of knee rest and exercise,KSS score and ROM of knee joint between two groups before operation and 3 days and 90 days after operation(P＞0.05).There was no significant difference in complications between two groups(P＞0.05).Conclusion Postoperative imaging of two robot systems showed good lower limb force line.The domestic HRATKA group had better LFC,FFC angle and HKA deviation angle than the imported BRATKA group,but there were no significant difference in postoperative knee function and pain relief.

Calcified lesions increase the difficulty of interventional therapy for coronary heart disease,and increase the risk of perioperative and long-term complications.Pretreatment of calcified lesions is very important.Coronary lithotripsy(IVL)is used more and more in calcified lesions,and many clinical trials have proved its effectiveness and safety.Stent underexpansion is an important risk factor for stent thrombosis and restenosis,which increases the incidence of complications.At present,there is no effective coping strategy or clear consensus or guidelines for the treatment of stent underexpansion caused by calcified lesions.There are few reports about the treatment of stent under expansion by IVL,and most of them are case reports and small sample studies.In this paper,two cases of stent under expansion were reported.After stent implantation,stent under expansion was found,and IVL was used to treat the cases,which achieved good results.This paper reports 2 cases of stent under expansion to explore the efficacy and safety of IVL in the treatment of such lesions.

Objective:To investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia(AML).Methods:The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group,and the children with high-risk AML who received idarubicin regimen were enrolled as controls,and their clinical data were analyzed.Time to bone marrow recovery,the complete remission rate of bone marrow cytology,the clearance rate of minimal residual disease,and treatment-related adverse reactions were compared between the two groups.Results:The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day),granulocytes(18 vs 24 day),platelets(17 vs 24 day),and hemoglobin(20 vs 26 day)compared with those treated with idarubicin,there were statistical differences(P＜0.05).The effective rate and MRD turning negative rate in the observation group were 90.9％and 72.7％,respectively,while those in the control group were 94.1％and 76.4％,with no statistical difference(P＞0.05).The overall response rate of the two groups of patients was similar.Conclusion:The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML,but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.

Objective:To summarize the clinical features of reversible posterior encephalopathy syndrome(PRES)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:The clinical data of six children who developed PRES after undergoing allo-HSCT in the Department of Hematology of Wuhan Children's Hospital from June 2016 to December 2022 were retrospectively analyzed,and their clinical characteristics,imaging examination,laboratory examination,and treatment regression were summarized.Results:Among 281 children underwent allo-HSCT,6 cases(2.14％)developed PRES,with a median age of 5.1(1.5-9.7)years old.4 cases underwent related haploidentical donor transplantation,and 2 cases underwent sibling allografting and unrelated donor allografting donor transplantation,respectively.All six children had an acute onset of illness,with clinical manifestations of nausea and vomiting,seizures,psychiatric disorders,visual disturbances.The five cases elevated blood pressure.All children with PRES were treated with oral immunosuppressive drugs during seizures,and 3 cases were combined with different degrees of graft-versus-host disease.Most of the children showed effective improvement in clinical symptoms and imaging after adjusting/discontinuing suspected medications(cyclosporine,etc.)and symptomatic supportive treatments(oral antihypertensive,diazepam for antispasmodic,mannitol to lower cranial blood pressure),and one of them relapsed more than 8 months after the first seizure.Conclusion:PRES is rare after hematopoietic stem cell transplantation in children,and its onset may be related to hypertension,cytotoxic drugs,graft-versus-host disease,etc.Most of them can be recovered after active treatment,but not completely reversible,and the prognosis of those who combined with TMA is poor.

Objective:To investigate the effect of integrin αvβ6 on lipid metabolism in colon cancer cells;to identify potential metabolic biomarkers for the diagnosis of colon cancer.Meth-ods:Liquid chromatography-mass spectrometry(LC-MS)-based lipidomic analysis was utilized to investigate the effects of αvβ6 on the changes in SW480 metabolism in colon cancer cell lines.The partial least squares discriminant analysis model showed different lipid profiles in Integrin αvβ6 over-expressed or low-expressed SW480.Results:After Integrin αvβ6 overexpression,a total of 252 lipids showed significant differences in SW480 cells,of which 138 showed up-regulation and 114 showed down-regulation.Moreover,the Methyl phosphatidylcholine(MePC),phosphatidyl-choline(PC),phosphatidylethanolamine(PE)and triglycerides(TG)were also found to have good diagnostic potential in αvβ6 overexpressing cancer cells.Conclusion:Integrin αvβ6 may promote cancer cell invasivness and metastasis by regulating pathways of dysregulated lipid metabolism.These results may provide potential clues to the molecular mechanisms of Integrin αvβ6 on colon cancer cells.

Objective:Exploring the surgical method and safety of robot assisted kidney transplantation (RAKT) with a kidney implanted through the vagina, currently there is no such surgery in China.Method:Retrospective analysis of the data of a 44-year-old postpartum woman with stage 5 chronic kidney disease admitted to the kidney transplantation ward of West China Hospital, Sichuan University on June 28, 2021. RAKT with a kidney inserted through the vagina was performed on the recipient. The transplanted kidney was cooled using continuous surface cooling technology (CSCT) using ice physiological saline. The recipient was followed up for 3 months after surgery. In addition, we searched the Wanfang database, China National Knowledge Infrastructure, VIP database, China Biomedical Literature Service System, PubMed, Embase, and Central databases. The Chinese search keywords were "robot kidney transplantation" and "vagina", while the English search keywords were "kidney transplantation" and "robot" and "vacuum". The literature was published from June 1990 to June 2022, and a detailed summary of all published cases was provided.Result:a perineal approach was used to open the posterior fornix of the vagina and the graft was successfully implanted. The surgery was successfully completed, with a total duration of 250 minutes, vascular anastomosis time of 45 minutes, and warm ischemia time of 63 minutes. The recipient recovered smoothly without vaginal pain and postoperative pain relief; There was also no abdominal infection. Using CSCT, the surface temperature of the graft was maintained at 10~16 ℃ during anastomosis. After literature review, a total of 12 cases of renal RAKT implantation through vagina have been reported. All cases were successful, except for one case where the graft was poorly positioned and converted to open surgery. The average surgical time reported in the literature is (210 ± 37) minutes, vascular anastomosis time is (41 ± 8) minutes, and warm ischemia time is (50 ± 10) minutes. There were no surgical complications.Conclusion:Transvaginal insertion of RAKT into the kidney is safe and feasible, but special types of recipients should be selected for this surgical method and evaluated before surgery.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.