OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Sodium-glucose cotransporter 2 inhibitor was initially developed and marketed as a novel oral hypoglycemic agent.Currently,it has been recommended as one of the main therapeu-tic agents for chronic heart failure by national and international guidelines,and it has a significant cardioprotective effect on heart failure with reduced ejection fraction,heart failure with im-proved ejection fraction,heart failure with mildly reduced ejec-tion fraction,and heart failure with preserved ejection fraction.However,cardiac tissues do not express sodium-glucose cotrans-porter 2,and the underlying mechanisms of clinical cardiovascu-lar benefits of sodium-glucose cotransporter 2 inhibitors remain unclear.This review intends to summarize the cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in clinical trials and the recommendations suggested by national and inter-national heart failure guidelines and to elucidate further the po-tential mechanisms of sodium-glucose cotransporter 2 inhibitor-mediated cardioprotective effects.

BACKGROUND:Quantitative measurement of knee laxity after partial anterior cruciate ligament injury is crucial for timely diagnosis,post-treatment,and rehabilitation.There is a lack of research on the use of articular ligament digital arthrometer in the diagnosis of partial anterior cruciate ligament injury.OBJECTIVE:To investigate the diagnostic value of a new articular ligament digital arthrometer in partial anterior cruciate ligament injury.METHODS:Totally 30 patients with partial anterior cruciate ligament injury and 20 healthy volunteers were included.The anterior tibial translation values under 80,120,and 150 N loads were measured by a homebred digital arthrometer.The anterior tibial translation and side-to-side difference were compared between the partial anterior cruciate ligament group and control group.The receiver operating characteristic curve was analyzed and area under curve was calculated,and the diagnostic sensitivity and specificity of the digital arthrometer were determined.RESULTS AND CONCLUSION:(1)There was no significant difference in age,sex,body mass index,and course of disease between the partial anterior cruciate ligament injury group and control group(P＞0.05).(2)The side-to-side difference values of the partial anterior cruciate ligament injury group were significantly higher than those of the control group(P＜0.05),and the anterior tibial translation values of the injured side were significantly higher than those of the healthy side in the partial anterior cruciate ligament injury group(P＜0.05).(3)When the load was applied at 80 N,the diagnostic accuracy was highest(cutoff value=10.45 mm);the area under curve was 0.813(95％CI:0.708-0.919),and the sensitivity and specificity were 76.7％and 70.0％,respectively.(4)It is indicated that the digital arthrometer can objectively and quantitatively evaluate knee laxity after partial anterior cruciate ligament injury,and provide objective diagnostic basis for patients with partial anterior cruciate ligament iniurv.

Objective:To analyze the changes of serum metabolites in patients with acute pancreatitis (AP) by non-targeted metabolomics method.Methods:Serum samples and clinical data of 15 AP patients hospitalized in the Affiliated Hospital of Jiangnan University from August to September 2024 were collected and included in the AP group, including 9 males and 6 females, aged (55.4±15.3) years. The serum and clinical data of 25 patients with colon polyps in the same hospital during the same period of time were collected, including 15 males and 10 females, aged (61.2±11.5) years, and were included in the control group. Serum metabolomic detection was performed using the ultra-high performance liquid chromatography tandem Fourier transform mass spectrometer. The modeling method was orthogonal partial least square discriminant analysis, and principal component analysis was performed on the data matrix to screen the differential metabolites in serum of AP patients. The Kyoto Encyclopedia database of Genes and Genomes was used to annotate differential metabolites, and the pathway of differential metabolite enrichment was analyzed by software.Results:The principal component analysis showed that the contribution ratio of the first principal component was 15.1%, the proportion of the second principal component was 10.8%, and the total proportion of the two was 25.9%. In principal component analysis, two groups of samples can be clearly distinguished and show obvious clustering characteristics. According to the analysis of OPLS-DA model, there were significant differences in serum metabolic profiles between AP group and control group. There were 683 differentially expressed metabolites between the two groups, with 367 differentially expressed metabolites up-regulated compared with the control group and 316 differentially expressed metabolites down-regulated compared with the control group. It is mainly Phosphatidic Acid (Lte4/8: 0) (+ 218%), Omeprazole Sulphone (-38%), and 2-(Propylthio) Nicotinic Acid (2-propyl thionicotinic acid) (-58%), Gein (salicyricetin) (-47%) and so on. Pathway enrichment analysis showed that the differential metabolites in AP patients were mainly concentrated in citric acid cycle, arginine biosynthesis and glycerophospholipid metabolism pathways.Conclusion:Serum metabolites in AP patients change significantly, including citric acid cycle, arginine biosynthesis, glycerophospholipid metabolism.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective:To analyze the changes of serum metabolites in patients with acute pancreatitis (AP) by non-targeted metabolomics method.Methods:Serum samples and clinical data of 15 AP patients hospitalized in the Affiliated Hospital of Jiangnan University from August to September 2024 were collected and included in the AP group, including 9 males and 6 females, aged (55.4±15.3) years. The serum and clinical data of 25 patients with colon polyps in the same hospital during the same period of time were collected, including 15 males and 10 females, aged (61.2±11.5) years, and were included in the control group. Serum metabolomic detection was performed using the ultra-high performance liquid chromatography tandem Fourier transform mass spectrometer. The modeling method was orthogonal partial least square discriminant analysis, and principal component analysis was performed on the data matrix to screen the differential metabolites in serum of AP patients. The Kyoto Encyclopedia database of Genes and Genomes was used to annotate differential metabolites, and the pathway of differential metabolite enrichment was analyzed by software.Results:The principal component analysis showed that the contribution ratio of the first principal component was 15.1%, the proportion of the second principal component was 10.8%, and the total proportion of the two was 25.9%. In principal component analysis, two groups of samples can be clearly distinguished and show obvious clustering characteristics. According to the analysis of OPLS-DA model, there were significant differences in serum metabolic profiles between AP group and control group. There were 683 differentially expressed metabolites between the two groups, with 367 differentially expressed metabolites up-regulated compared with the control group and 316 differentially expressed metabolites down-regulated compared with the control group. It is mainly Phosphatidic Acid (Lte4/8: 0) (+ 218%), Omeprazole Sulphone (-38%), and 2-(Propylthio) Nicotinic Acid (2-propyl thionicotinic acid) (-58%), Gein (salicyricetin) (-47%) and so on. Pathway enrichment analysis showed that the differential metabolites in AP patients were mainly concentrated in citric acid cycle, arginine biosynthesis and glycerophospholipid metabolism pathways.Conclusion:Serum metabolites in AP patients change significantly, including citric acid cycle, arginine biosynthesis, glycerophospholipid metabolism.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.