Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

Objective To explore the pro-inflammation resolution and protective effects of reactive oxygen species (ROS)-responsive liposomes modified with a cardiac-targeted peptide and loaded with resolvin D1 (RvD1, C-LP-RvD1) on myocardial ischemia-reperfusion (MI/R) injury. Methods The C-LP-RvD1 nanoliposomes were constructed, characterized physically and chemically, and evaluated for in vitro release. Non-targeting peptide-modified drug-loaded liposomes (LP-RvD1) were served as controls. Apoptotic adult mouse cardiomyocytes (AMCMs) were used to verify in vitro targeted binding capacity of C-LP-RvD1. In MI/R mice models, the in vivo distribution and cardiac enrichment of C-LP-RvD1 were assessed. Levels of specialized pro-resolving mediator (SPM) and inflammatory factors in cardiac tissue homogenates and cell culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Cardiac function and fibrosis remodeling were evaluated via echocardiography and Masson staining four weeks after treatment. Biosafety was evaluated in healthy mice injected by C-LP-RvD1. Results The C-LP-RvD1 exhibited good nanoscale uniformity and stability, with ROS-triggered accelerated release characteristics. In vitro experiments showed that C-LP-RvD1 had higher binding capacity to apoptotic AMCMs than LP-RvD1, with significantly higher SPM levels (P＜0.01) and lower inflammatory factor levels (P＜0.05). In vivo experiments indicated enhanced cardiac enrichment of C-LP-RvD1 in MI/R injured hearts, with higher local myocardial SPM levels and lower inflammatory factor levels compared to LP-RvD1 (P＜0.05). Four weeks after treatment, compared with LP-RvD1, the C-LP-RvD1 mice group showed improved cardiac function indicators and reduced ventricular fibrosis remodeling ratio (P＜0.05). Safety evaluation revealed no significant systemic inflammation, immunogenicity, or coagulation abnormalities in healthy mice, with liver and kidney function and major organ histology showing no notable damage. Conclusions C-LP-RvD1 improves effective delivery of RvD1 to MI/R injured hearts through injury-targeted enrichment and ROS-responsive release, promoting inflammation resolution and suppressing excessive inflammation, thereby improving cardiac function and reducing adverse remodeling, with favorable biosafety.

Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

Objective: To investigate the hemolytic phenotypes of Staphylococcus aureus clinical isolates． Methods: The hemolytic phenotypes of 105 Staphylococcus aureus isolates were analyzed and summarized using the three-point inoculation method．Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of four hemolysin genes (hla，hlb，hlc，and hld) ; The VITEK 2 GP639 antimicrobial susceptibility card was used to detect resistance to commonly used antibiotics ; DNA gel electrophoresis was performed to determine the prevalence of the mecA，sea，tst，and pvl genes ; The microtiter plate crystal violet staining method was used to assess biofilm formation ability ; The CCK-8 assay was used to evaluate cytotoxicity against macrophages． Results: Seven hemo- lytic phenotypes were identified among the Staphylococcus aureus clinical isolates． Differences were found among Staphylococcus aureus clinical isolates with different hemolytic phenotypes in terms of mRNA expression levels of he- molysin genes，antibiotic resistance，virulence gene prevalence，biofilm formation ability，and cytotoxicity to mouse macrophages (P ＜0. 05 ) ． Conclusion Staphylococcus aureus clinical isolates exhibit diverse hemolytic pheno- types，which should be a focus across multiple dimensions，including microbiological testing，clinical treatment， and nosocomial infection prevention and control．

Antimicrobial resistance(AMR)is a growing public health crisis that requires innovative solutions.Emerging multidrug resistant(MDR)Salmonella typhimurium has raised concern for its effect on path-ogenic infection and mortality in humans caused by enteric diseases.To combat these MDR Salmonella typhimurium pathogens,highly effective and broad-spectrum antibiotics such as flufenicol(FFC)need to be evaluated for their potent antibacterial activity against Salmonella typhimurium.However,the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR.In this work,we develop a novel nano-formulation,flufenicol nano-micelles(FTPPM),which are based on D-α-tocopherol polyethylene glycol 1,000 succinate(TPGS)/poloxamer 188(P188),for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine.Herein,FTPPM were prepared via a thin film hydration method.The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems,which can further decrease pro-duction costs.The optimized FTPPM demonstrated outstanding stability and sustained release.An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy(68.17％)than did florfenicol-loaded TPGS polymer micelles(FTPM),flufenicol active pharmaceutical ingredients(FFC-API),and flufenicol commercially available medicine(FFC-CAM),and also exhibited outstanding biocompatibility.Notably,FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms.More importantly,FTPPM effectively restored intestinal flora dis-orders induced by drug-resistant Salmonella typhimurium in mice.In summary,FTPPM significantly improved the solubility and oral bioavailability of florfenicol,enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo.FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.

AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To investigate the impact of the interval between neoadjuvant immunotherapy combined with chemotherapy(nICT) and surgery on pathological outcomes and prognosis in patients.Methods:This is a retrospective cohort study. A total of 115 patients with locally advanced esophageal squamous cell carcinoma who underwent nICT followed by sequential surgery at Department of Thoracic Surgery, Peking University People′s Hospital or Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2024 were included. Among them, 99 were male and 16 were female, with an age of ( M(IQR)) 65 (11) years (range:45 to 81 years). All patients received 2 to 6 cycles of paclitaxel plus platinum-based doublet chemotherapy combined with PD-1 immune checkpoint inhibitors. The resectability of tumors was assessed based on CT scans of the chest and abdomen, and surgical approaches included Sweet surgery, Mckeown surgery, and Ivor-Lewis surgery. Patients were divided into a short-interval group (4 to <6 weeks) and a long-interval group (6 to 12 weeks) based on the interval between neoadjuvant immunochemotherapy and surgery. General patient data, surgical details, pathological response, and prognosis were collected and analyzed. Data comparisons were performed using independent sample t-test, Mann-Whitney U test, χ 2 test, or Fisher′s exact test. Multivariate logistic regression analysis was used to identify independent factors influencing pathological complete response (pCR). Survival analysis was conducted using the Kaplan-Meier method and Log-rank test. Results:There were no significant differences in baseline characteristics, neoadjuvant treatment details, surgical outcomes, or postoperative complications between the long-interval group and the short-interval group (all P>0.05). Multivariate Logistic regression analysis revealed that, among clinical factors, interval between neoadjuvant immunochemotherapy and surgery was significantly associated with pCR (long-interval group vs. short-interval group: OR=4.14, 95% CI:1.63 to 10.50, P=0.003). The pCR rate was higher in the long-interval group (43.6% vs. 17.1%, χ2=6.48, P=0.011). Survival analysis showed no significant differences in overall survival ( P=0.094) or disease-free survival ( P=0.840) between the two groups. Conclusion:Appropriately extending the surgical interval after neoadjuvant immunochemotherapy maybe lead to a higher pCR rate, without increasing surgical difficulty or damaging prognosis.

Objective To study the clinical efficacy of buccal acupuncture in the treatment of refractory tinnitus in the elderly.Methods In this study,50 elderly patients with refractory tinnitus were randomly divided into two groups:the experimental group(n=26)received buccal acupuncture therapy on the neck,upper neck,scapula zone,shoulder,back,mastoid process,thoracic plexus,abdominal plexus and pelvic plexus on the affected side,and the control group(n=24)received sound therapy.After 8 weeks of treatment intervention,the two groups were comprehensively evaluated for the changes in the tinnitus evaluation scale(TEQ),self-rating depression scale(SDS),and blood rheological indexes,including whole blood high-cut viscosity(HSV),plasma viscosity(PSV)and fibrinogen in blood(FIB)clotting.Results After treatment,the total effective rate of the experimental group was 84.6％(22/26),higher than 54.2％(13/24)in the con-trol group.The difference in total effective rate and efficacy level between the two groups was statistically significant(P＜0.05).TEQ and SDS were significantly lower in the two groups compared to pre-treatment(P＜0.05),and HSV,PSV and FIB in the experimental group were significantly lower compared to pre-treatment(P＜0.05).The experimental group demonstrated better post-treatment outcomes in TEQ,SDS,HSV,and FIB compared to the control group(P＜0.05).Conclusion Buccal acupuncture treatment is effective in improving the symptoms of refractory tinnitus in the elderly,relie-ving the depression complicated by tinnitus,and is helpful in changing blood flow resistance and reducing blood coagulation probably.