AIM: To investigate and clarify the intervention mechanism of trigonelline(TRG)in preventing ferroptosis in ARPE-19 cells based on the Nrf2/HO-1/GPX4 pathway.METHODS: The ARPE-19 cells were cultured and subsequently treated with varying concentrations of trigonelline to ascertain the most effective concentration for modulating the cells. Then the cells were categorized into distinct groups, including normal control(NC)group, high glucose(HG)group, Fer-1 group, TRG group based on the determined concentration. Samples from each group were then gathered to assess relevant indicators. The intracellular levels of glutathione(GSH), malondialdehyde(MDA), and Ferrion were quantified in accordance with the protocols provided by the GSH, MDA, and Ferrion detection kits. Flow cytometry was employed to measure the ROS levels within each group. Additionally, Western blot analysis was conducted to examine the expression of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase(GPX4), and acyl-CoA synthetase long-chain family member 4(ACSL4)across the different groups.RESULTS: The preconditioning intervention with 40 μg/mL TRG effectively mitigated the decline in cell activity induced by high glucose levels. The levels of reactive oxygen species(ROS)and MDA in the HG group were markedly elevated compared to the NC group; and the TRG group exhibited significantly reduced levels of ROS and MDA compared to those of the HG group, with the antioxidant stress index GSH showing opposite trends to those of ROS and MDA across all the groups. Whereas the Fer-1 and TRG groups showed decreased expression levels of ACSL4 protein and iron ions, and the expression levels of Nrf2, HO-1 and GPX4 in the Fer-1 and TRG groups were increased.CONCLUSION: TRG protects ARPE-19 cells from the detrimental effects of high glucose by targeting the Nrf2/HO-1/GPX4 signaling pathway to counter ferroptosis.

Objective To investigate the value of ¹⁸F-FDG PET/CT metabolic parameters in the prognostic assessment of nasopharyngeal cancer patients. Methods The clinical data and PET/CT metabolic parameters of 185 nasopharyngeal cancer patients were retrospectively analyzed. The collected parameters were SUV_max, MTV, TLG, total metabolic tumor volume (TMTV) and whole-body total lesion glycolysis (WTLG). The ROC curve was used to determine the optimal cut-off values of PET/CT metabolic parameters. Univariate and multivariate Cox regression models were used to screen the independent prognostic factors. Kaplan–Meier curves were used to analyze the survival differences. Results The results of univariate Cox regression analysis showed that age, pathologic type, WTLG, TMTV, MTV, and TLG were closely associated with OS and PFS; and SUV_max was associated with PFS (P<0.05). Multivariate Cox regression analysis results showed that age, TMTV, and WTLG were the independent prognostic factors for OS and PFS (P<0.05). The combination of WTLG with T/N staging (AUC=0.781 and 0.781) and TMTV with T/N staging (AUC=0.800 and 0.790) yielded greater predictive accuracy than that of WTLG and TMTV alone (AUC=0.724 and 0.719) or T/N staging (AUC=0.593 and 0.575). Conclusion TMTV and WTLG are important prognostic predictors of nasopharyngeal carcinoma. TLG and MTV of primary lesions are prognostic factors for patients’ PFS and OS. SUV_max has limited prognostic value. Systemic metabolic indexes (TMTV and WTLG), when combined with T/N staging, can optimize prognostic stratification.

In the process of exploring standardized and efficient ethical review models for multi-center drug clinical trials, the ethical review alliance emerged as the times require. Compared with mature ethics committees, higher requirements have been put forward for the "young" ethics committees. By analyzing problems existing in review work of "young" ethics committees in the ethics review alliance, this paper discussed the measures to improve the review quality of "young" ethics committees and promote the standardized and efficient operation of the alliance, and put forward countermeasures and suggestions for improving the homogenization of ethics review and accelerating the clinical research process of innovative drugs.

Objective To investigate assess the bidirectional causal relationship between ulcerative colitis(UC)and hypothyroidism using a two-sample Mendelian randomization(TSMR).Methods Single nucleotide polymorphism(SNP)data relevant to UC and hypothyroidism were retrieved from the Finnish Biobank and the IEU database,respectively.Independent SNPs strongly associated with UC were selected as instrumental variables.Causal associations between UC and hypothyroidism were evaluated using the inverse variance weighted(IVW)method,MR-Egger regression,and weighted median estimator.Additionally,MR-PRESSO was employed to assess the hori-zontal pleiotropy and outlier SNPs.Cochran's Q test and funnel plots were performed to evaluate the heterogeneity among the SNPs.A leave-one-out analysis was conducted to examine the influence of individual SNPs on causal assessments.Results Four instrumental variables strongly associated with UC were identified.The IVW method indicated a causal relationship between UC and hypothyroidism(OR = 0.975,95%CI:0.924～0.990,P = 0.011).Cochran's Q test yielded a Q statistic of 2.566 with a p-value of 0.463,suggesting no heterogeneity among the SNPs.Both MR-Egger(P = 0.523)and MR-PRESSO(P = 0.548)tests suggested the absence of horizontal pleiotropy.However,the results of the reverse TSMR did not support a reverse causal relationship.Conclusion The findings from the TSMR analysis reveal a negative causal relationship between UC and hypothyroidism.

BACKGROUND:This review explores the current research status and frontier hot spots of functional magnetic resonance imaging(fMRI)in the field of traditional Chinese medicine(TCM)for the treatment of ischemic stroke,and attempts to grasp future research trends,with a view to providing a reference for subsequent research in this field. OBJECTIVE:To visualize and analyze the hotspots and frontiers in the TCM treatment of ischemic stroke based on fMRI using CiteSpace knowledge mapping combined with binary logistic regression equations,in order to grasp the future research trends and further explore the distribution of brain regions with abnormal neural activity related to the types of post-stroke dysfunction. METHODS:CNKI,WanFang,VIP,Chinese Biomedical Literature Database and Web of Science core set database were searched.CiteSpace was used to plot keyword co-occurrence,keyword clustering timeline,burst term detection,co-cited literature mapping to analyze hotpots and frontiers in this field.Binary logistic regression analysis fitted the distribution of brain regions with abnormal neural activity associated with different dysfunction after ischemic stroke. RESULTS AND CONCLUSION:A total of 354 articles were included for CiteSpace knowledge mapping analysis.The number of annual publications showed that the research popularity has been raised from 2000 to 2022 with a good development prospect,but the core strength is mainly concentrated in China.Keywords co-occurrence and clustering time line analysis showed that aphasia,hemiplegia and cognitive impairment are the hot poststroke dysfunction types.Electroacupuncture,acupuncture and head acupuncture are hotspot intervention measures.Functional connectivity is a hotspot analysis method,and resting fMRI is a hotspot scanning technology.The time span of each research hotspot is long,indicating that it has a certain research value and the relevant research is gradually deepening,promoting the research progress in this field.However,acupuncture is the main intervention measure,and there is a lack of research on traditional Chinese medicine,Chinese patent medicine,acupuncture and medicine combination and other TCM therapy.Burst term detection results showed that functional connectivity,graph theory,degree centrality,default mode network,randomized controlled trials have great influence and strong explosive power.They are the current and future frontier hot spots in this field,suggesting that future research should focus on the brain network information integration and strengthen the scientific and rigorous clinical trial design.The results of co-cited literature analysis showed that the epidemiological investigation of ischemic stroke,the safety and effectiveness of acupuncture in the treatment of stroke,the brain activation patterns under different tasks,and the neuropathological mechanism of brain network dysfunction after stroke are the theoretical basis of this field.Future research direction in this field is to explore TCM-targeted brain regions and neural networks to reveal the brain effect mechanism of TCM promoting neural remodeling after stroke.A total of 255 articles were included for binary Logistic regression analysis.The results showed that sensorimotor cortex and premotor area dysfunction are positively correlated with the incidence of motor dysfunction after stroke;hippocampus,cerebellum posterior lobe,precuneus,inferior temporal gyrus and anterior cingulate nerve dysfunction are positively correlated with the incidence of cognitive impairment after stroke;cuneus,angular gyrus and prefrontal lobe neural dysfunction were positively correlated with the incidence of affective disorder after stroke;anterior cingulate,cerebellum posterior lobe neural dysfunction are positively correlated with the incidence of swallowing disorder after stroke.The above brain regions are the core brain regions of the sensorimotor network,default mode network and reward loop,suggesting that functional abnormalities within or between brain networks related to dysfunction may be potential target areas for TCM intervention,but the specific changes in neural activity activation or inhibition still need to be refined.

Objective To analyzes the Chinese and English literature of anti-tumor of licorice based on CiteSpace knowledge graph,and explores the research status,research hotspots and trends.Methods CiteSpace 6.2.R4 software was used to visually analyze the Chinese and English literature on licorice anti-tumor from January 2002 to September 2023 included in CNKI and Web of Science,and visually analyzed the research topics such as the number of publications,authors,institutions,journals,funds,and keywords.Results A total of 397 Chinese articles and 172 English articles were included after screening.The analysis of the authors of Chinese and English literature shows that Zheng Qiusheng and Jung are the authors with the largest number of anti-tumor articles in Chinese and English respectively,while Beijing University of traditional Chinese Medicine and Hallym University have the largest number of articles in Chinese and English respectively,and there is relatively more cooperation among research institutions in English literature.Chinese and English keyword analysis shows that the anti-tumor research of Glycyrrhiza uralensis mainly focuses on breast cancer,licorice and its active components,molecular mechanism and so on.Cluster analysis shows that research has focused on the active ingredients and clinical applications of licorice;Traditional Chinese Medicine treatment theory and commonly used compound medicines;Experimental research and mechanism of action of licorice on anti-tumor effects;Research on the mechanism of licorice in preventing and treating nephrotoxicity and other toxic side effects caused by chemotherapy drugs.Conclusion The study of anti-tumor mechanism of licorice and the combination of licorice and natural products may be the focus of future research.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. 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 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor.Methods:Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed.Results:Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively.Conclusions:SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

【Objective】 To discuss the effect of adding tranexamic acid(TXA) during surgery on blood loss and security during short segment lumbar spinal stenosis surgery. 【Methods】 One hundred and eight patients with lumbar spinal stenosis who were to undergo lumbar posterior fusion surgery were randomly divided into control group, TXA group and adding TXA group, with 36 patients in each group. In the control group, TXA was not used during surgery.The TXA group received intravenous infusion of 100 mL normal saline mixture containing 1 g of TXA 15 minutes before surgery after anesthesia. In adding TXA group, after the same operation in TXA group, 10 mg/kg(body weight) of TXA was infused 3 hours later. Total perioperative blood loss, dominant blood loss, hidden blood loss, intraoperative blood loss, postoperative drainage volume, and transfusion rate were recorded in the two groups. Hemoglobin (Hb), hematocrit(HCT), prothrombin time international standardized ratio (PT-INR), prothrombin time(PT), activated partial thromboplastin time(APTT), blood platelet count (BPC), D-dimer (D-D), fibringen(FIB), C-reactive protein (CRP), alanine aminotransferase (ALT), blood urea nitrogen (BUN) were measured 3 days before and after the surgery in the three groups. Postoperative adverse events were followed up. 【Results】 The total blood loss(mL) [(968.7±209.6) vs (1 369.8±276.3), (968.7±209.6) vs (1 273.9±250.2)], dominant blood loss(mL) [(590.5±164.3) vs (876.4±235.9), (590.5±164.3) vs (789.3±221.7)], intraoperative blood loss(mL) [(318.7±120.7) vs (457.8±146.6), (318.7±120.7) vs (423.9±162.3)] and postoperative drainage volume(mL) [1 day after surgery: (164.6±25.0) vs (262.3±51.7), (164.6±25.0) vs (219.8±37.1); 3 days after surgery: (107.2±18.6) vs (156.3±37.6), (107.2±18.6) vs (145.3±22.3)] of the adding TXA group were lower than those of the control group and TXA group (P<0.05), and the transfusion rate was lower than that of the control group (P<0.05).The postoperative drainage volume and transfusion rate of TXA group were lower than that of the control group (P<0.05).There was no statistical difference in the amount of hidden blood loss between the three groups (P>0.05). Compared with the preoperative results, Hb, Hct and BPC in the three groups decreased (P<0.05), and D-D, FIB and CRP increased (P<0.05), but the change degree of Hb, Hct, BPC, D-D and CRP in the TXA group and the adding TXA group was less than that in the control group (P<0.05), and the change degree of Hb, Hct, BPC, D-D and CRP in the adding TXA group was less than that in the TXA group (P<0.05).There was no statistically significant difference in PT-INR, PT, APTT, ALT and BUN between and within the three groups before and after surgery (P>0.05), and all of them were within the normal range. No serious adverse events such as deep vein thrombosis, pulmonary embolism, epilepsy, liver and kidney damage were found in all patients after postoperative follow-up. 【Conclusion】 Intraoperative addition of TXA can effectively reduce the amount of blood lost during short segment lumbar spinal stenosis surgery without increasing the risk of complications such as coagulation disorders, thrombosis, liver and kidney function damage.