Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Iron is involved in several activities in the brain, including energy metabolism, neurotransmitter transmission, and myelination. Disorder of peripheral iron metabolism and excessive iron accumulation in the brain can reduce cognitive and behavioral ability through pathological mechanisms such as inflammatory response and abnormal protein expression, leading to cognitive disorders. Quantitative susceptibility mapping (QSM), as a new non-invasive magnetic resonance technique, can quantitatively measure brain iron deposition, clarify the relationship between cognitive disorders and iron homeostasis imbalance, and provide a basis for clinical diagnosis and treatment of the diseases. This article reviews the latest research progress of QSM in brain iron deposition associated with cognitive disorders.

Objective:To explore the feasibility, safety, and effectiveness of a novel suture instrument for closure of full thickness defects of the gastric wall under gastroscopy.Methods:Ten pigs were used as experimental animals. Perforation model (30 mm in long diameter) was created in the stomach of each pig. The perforations were then closed by the novel suture instrument under gastroscopy. The completion time and efficacy of each perforation repair were recorded. The pigs were euthanized 14 days after the procedure. The healing condition was observed under gastroscopy. A postmortem examination was performed to observe the abdominal infection and healing condition of perforation. Ascites sample was taken for bacterial culture.The stomach biopsy were taken for histopathologic examination.Results:All gastric perforation models in the 10 pigs were established successfully. Endoscopic closure for the stomach perforation was technically successful in all 10 pigs. The procedure time was 34.10±10.32 minutes. All animals survived. Gastroscopy and necropsy showed that the perforation healed well with local adhesion. One pig developed abdominal infection. Ascites culture were negative in 9 cases, 1 bacterial infection was caused by Arcanobacterium pyogenes and Escherichiacoli. The pathology results showed that the muscular layer of the gastric wall defect in the entire group was well repaired. Conclusion:The novel suture instrument is safe and effective in repairing full-thickness gastric wall defects under ordinary single clamp gastroscopy, providing an experimental basis for further clinical research.

Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

Objective To explore the value of magnetic resonance imaging(MRI)T2-weighted imaging(T2WI)and diffusion-weighted imaging(DWI)sequences in evaluating the therapeutic effect of neoadjuvant chemoradiotherapy(nCRT)for advanced rectal cancer.Methods A retrospective analysis was conducted on 124 patients with advanced rectal cancer who received nCRT from November 2020 to November 2023 in Dazhou Integrated TCM&Western Medicine Hospital.All patients underwent radical resection of rectal cancer at 6-8 weeks after the end of nCRT.MRI scans were performed before nCRT and at 6-8 weeks after the end of nCRT.The differences in tumor long and short diameters,signal intensity in tumor(SIT),apparent diffusion coefficient(ADC)and other parameters were measured,and the MRI tumor regression grade was analyzed.Surgery was performed at 3 days after the second examination.The patients were divided into grade 0-1 group and grade 2-3 group according to the postoperative pathological tumor regression grade.The differences of MRI parameters before and after treatment were compared between groups.The consistency of T2WI sequence and DWI sequence in the diagnosis of tumor regression grade after nCRT was analyzed.ROC curve was used to analyze the value of MRI parameters in evaluating the therapeutic effect of nCRT.Results The differences of tumor long diameter,short diameter,SIT and ADC measured by twice MRI examination in grade 0-1 group were increased as compared with grade 2-3 group(P<0.05).MRI detected MRI tumor regression grade 1 in 28 cases(22.58%),grade 2 in 30 cases(24.19%),grade 3 in 31 cases(25.00%),grade 4 in 25 cases(20.16%)and grade 5 in 10 cases(8.06%).Consistency analysis showed that MRI had a sensitivity,specificity,accuracy rate and Kappa value of 92.45%,87.32%,89.51%and 0.788 in evaluating postoperative tumor regression grade.ROC analysis revealed that the AUC of MRI parameters such as differences in tumor long diameter,short diameter,SIT and ADC measured by twice MRI examinations in evaluating the nCRT efficacy ranged from 0.827 to 0.921,and the AUC of combined evaluation was 0.928(P<0.05).Conclusion The combined evaluation of MRI T2WI and DWI sequences can be served as an effective tool for evaluating the therapeutic effect of nCRT for advanced rectal cancer.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective To investigate the clinical effect of aribulin combined with vinorelbine+cisplatin(NP)regimen in the treatment of advanced breast cancer patients.Methods Eighty patients with advanced breast cancer were selected and divided into the conventional group(treated with chemotherapy using NP regimen)and the combined group(treated with aribulin combined with NP regimen),with 40 cases in each group.The clinical benefit rate(CBR),objective response rate(ORR)and overall efficacy of the two groups were compared.Patients were followed for 12 months.The progression-free survival(PFS)was recorded in the two groups of patients.Serum levels of vascular endothelial growth factor(VEGF)A,VEGFB and VEGFC before treatment and 4 cycles after treatment were detected by enzyme-linked immunosorbent assay(ELISA).Adverse reactions of patients were evaluated and graded according to common adverse event evaluation criteria.Results The ORR and CBR of the combined group were significantly higher than those of the conventional group,and the overall curative effect of the combined group was better than that of the conventional group(P＜0.05).PFS in the combination group was longer than that in the conventional group(P＜0.01).After treatment,the levels of VEGFA,VEGFB and VEGFC in the 2 groups were lower than those before treatment,and the levels in the combined group were significantly lower than those in the conventional group(P＜0.05).The main adverse reactions of 2 groups during treatment were grade Ⅰto Ⅱ,including neutropenia,gastrointestinal reaction,peripheral nerve abnormality,fatigue,liver function injury and alopecia,with no statistical significance.Conclusion Aribulin combined with NP regimen in the treatment of advanced breast cancer can increase CBR and decrease VEGF expression level,with good safety.

Aiming at solving problems of ambiguous objectives,fragmented contents,fossilized forms,and single assess-ments in ideological and political education,a new course pattern have been constructed based on reestablishing course objectives,re-constructing teaching contents and resources,and reforming teaching models and evaluation systems through transition of course con-cept and promotion of online-and offline-blended course.Considering culture features of Immunology,diverse teaching activities were implemented.A cultural atmosphere of"happy learning,beauty orienting,thought discriminating,and practice devoting"have been created and the goal of ideological and political education with definite objectives,systematic contents,various forms,and multiple as-sessments have been archived.At the end of the term,a survey on the teaching effects of ideological and political education revealed that 99.3%of students felt moved,touched,and gained a lot during the ideological and political education.Remodeling the curriculum culture blazes a new path for ideological and political education in Medical Immunology.