Objective:To analyze the clinical characteristics of warfarin-related nephropathy (WRN).Methods:Medical records of patients with WRN admitted to Linyi People′s Hospital Affiliated to Shandong Second Medical University from January 1, 2020 to December 31, 2024 were collected. The patients′ basic information (gender, age), warfarin medication details (indications, dosage, frequency, etc.), comorbidities, concomitant medication usage, international normalized ratio (INR) and serum creatinine (Scr) test results before and after the occurrence of WRN, as well as the clinical manifestations, interventions, and outcomes of WRN were extracted. The causal relationship between warfarin and renal dysfunction was evaluated according to the Adverse Drug Reaction Reporting and Monitoring Manual. The clinical data of patients were descriptively and statistically analyzed. Results:A total of 11 patients were entered in the analysis, including 7 males and 4 females; the age ranged from 49 to 85 years, with a median age of 70 years, and 9 cases were older than 60 years. The causality evaluation showed that 3 patients were definite and 8 patients were probable. All the 11 patients had at least one comorbidity, including 6 cases of heart failure, 6 cases of hypoproteinemia, 4 cases of chronic kidney disease, 3 cases of hypertension, 3 cases of pulmonary infection, and 1 case of diabetes. Seven patients were treated with warfarin combined with broad-spectrum antibiotics, 6 combined with diuretics, and 3 combined with renin angiotensin system blockers. The time from the highest INR to the highest Scr level was 0-6 days, with a median time of 2 days, and it was ≤2 days in 9 patients. Six patients had bleeding manifestations such as microscopic hematuria, melena, epistaxis, hematochezia, and skin ecchymosis. Among the 11 patients, 10 stopped warfarin immediately and 1 reduced dosage. All patients received different doses of vitamin K 1 according to the INR level. Among the 6 patients of bleeding, 4 received symptomatic treatments such as omeprazole, tranexamic acid, somatostatin, thrombin powder and octreotide, and 2 patients received hemodialysis due to high Scr level. One patient with severe anemia received blood transfusion. After 1-5 days of treatments (with a median time of 2 days), the INR in all patients decreased to <3.00, of which 5 patients continued to take warfarin, 1 changed warfarin to rivaroxaban, and 5 did not continue anticoagulation therapy. After 2 to 14 days of treatments, Scr in 8 patients recovered to the reference value range, and Scr in 3 patients was still at a high level, of which 1 patient died of unexplained cardiac arrest. Conclusions:WRN is a common adverse reaction of warfarin, with or without bleeding. After the occurrence of WRN, the drug should be stopped as soon as possible and symptomatic treatment should be given. The prognosis is generally good, but it may also lead to chronic kidney disease.

To evaluate the analytical performance of a specific IgE (sIgE) quantitative detection system and explore the clinical application effect of dust mite extract and component detection. The fluorescent magnetic particle chemiluminescence method was used to verify the analytical performance of sIgE for house dust mite (D1), dust mite (D2) extracts, and their components (Der p 1, Der p 2, Der p 10, and Der p 23), including precision, limit of blank (LoB), limit of detection (LoD), linear range, and interfering factors. This is a retrospective cohort study. A total of 50 patients with allergic rhinitis and 50 patients with allergic asthma diagnosed at Zhongshan Hospital Affiliated to Fudan University from January 2022 to August 2023 were selected, along with 70 apparently healthy individuals who underwent physical examinations in the hospital as the healthy control group. The positive rates of each sIgE component in the three groups were compared, and the receiver operating characteristic (ROC) curve for diagnosing dust mite allergy was plotted. The results showed that the fluorescent magnetic particle chemiluminescence method for detecting sIgE demonstrated good repeatability and intermediate precision within the range of 0.1-100 kU/L. The LoB, LoD, and linear range all met the specified requirements. Except for Der p 10, which was interfered by the presence of conjugated bilirubin and free bilirubin (exceeding 40 mg/dl), the detection of other allergens was not significantly affected by common endogenous substances. In healthy individuals, 10% had positive sIgE for dustmite extract; in asthmatic and allergic rhinitis patients, the positive rates were 70% and 82%, respectively. The double positive rate of D1 and D2 in the healthy group was 8.6%, while in asthmatic and allergic rhinitis patients, it was 66% and 70%, respectively. When 0.35 kU/L was used as the threshold, the sensitivity of sIgE for dust mite extract to predict component positivity was 100%, specificity was 61.5%, positive predictive value (PPV) was 80.2%, and negative predictive value (NPV) was 100%. When the threshold was optimized to 0.78 kU/L, the sensitivity was 96.8%, specificity was 92.1%, PPV was 95.2%, and NPV was 94.6%. In conclusion, the repeatability, intermediate precision, LoB, LoD, linear range, and anti-interference ability of the fluorescent magnetic particle chemiluminescence method for detecting sIgE meet the requirements of laboratory quality management. This ensures detection quality, meets clinical needs, and can be used for the auxiliary diagnosis of allergic diseases.

Objective:To establish and optimize an autoverification system for thyroid function test reports of 5 items using historical test data.Methods:Based on the docoment' Autoverification of Clinical Laboratory Quantitative Test Results′, CLSI AUTO 10-A and AUTO 15 guidelines, an autoverification system for thyroid function test reports of 5 items was established combining with manual verification experience. A total of 193 860 thyroid function test reports of 5 items in 2021 were collected for the assessment of the original system. Totally 210 097 thyroid function test reports of 5 items in 2022 and 299 198 reports in 2023 were collected for the optimization of the autoverification system. There were 160 666 thyroid function test reports of 5 items from the first half of 2024 for the manual and autoverification comparison after optimization.Results:The pass rate of the autoverification system based on original thyroid function report in 2021 was 69.56%(134 849/193 860). The optimized system utilizing historical data from 2022 and 2023 covered 21 pattern rules and established verification for different patterns including range rules, delta check rules, and review rules. Taking manual verification as the standard for the data from the first half of 2024, the sensitivity and specificity of the optimized system were 100% (499/499) and 81.57% (130 646/160 167), respectively, with a false-negative rate of 0. The concordance rate between autoverification and manual verification was 81.63% (131 145/160 666), and the pass rate was 81.32% (130 646/160 666).Conclusion:Establishing and optimizing the autoverification system for thyroid function tests of 5 items using historical test data, and formulating verification rules for different patterns can be applied to clinical practise, which not only ensures the accuracy of test reports but also improves work efficiency, allowing continuously optimized and perfected of the system.

Objective:To evaluate the diagnostic performance of the 0-2 h high-sensitivity cardiac troponin T (hs-cTnT) cutoff recommended by the guidelines for the rule-out and rule-in diagnosis of suspected non-ST-segment elevation myocardial infarction (NSTEMI) patients of different age groups.Methods:This is a retrospective cohort study. Clinical data of 4 050 suspected NSTEMI patients who visited the Chest Pain Center of Zhongshan Hospital affiliated with Fudan University from January 2020 to December 2021 were retrospectively analyzed. Patients who visited from January 2020 to April 2021 (2 650 patients) were included as derivation cohort, and those who visited from May to December 2021 (1 400 patients) were included as validation cohort. The diagnostic performance of the guideline-recommended hs-cTnT 0-2 h cutoff for the rule-out and rule-in of NSTEMI diagnosis was compared among subgroups of patients aged ≤60, >60-70, and >70 years in the derivation group. Rule-out sensitivity, negative predictive value, and rule-out proportion, rule-in specificity, positive predictive value, and rule-in proportion were assessed. Cutoffs were established for subgroups with relatively lower diagnostic performance and validated in the validation group. Major adverse cardiovascular events (MACE) within 30 days after patient visit were used as the outcome, and survival curves were plotted using Kaplan-Meier curves, log-rank tests were used to analyze the incidence of MACE.Results:The sensitivity for ruled-out NSTEMI using the guideline-recommended 0-2 h cutoff in the subgroups of patients aged ≤60, >60-70, and >70 years in the derivation group was 100%; the negative predictive value was 100%; the ruled-out rates were 47.6% (331/696), 45.9% (491/1 070), and 28.5% (252/884), respectively. The specificity for ruled-in NSTEMI was 88.3%, 90.9%, and 86.4%, respectively; the positive predictive values were 55.3%, 59.3%, and 58.2%, respectively; the ruled-in rates were 22.6% (157/696), 19.5% (209/1 070), and 27.0% (239/884), respectively. With a requirement of sensitivity and negative predictive value >99%, the ruled-out cutoff for the subgroup of patients aged >70 years in the derivation group was established as 0 h hs-cTnT <6 ng/L or 0 h hs-cTnT<22 ng/L and 0-2 h Δhs-cTnT <5 ng/L, which increased the ruled-out rate of the subgroup aged >70 years to 45.6% (403/884). In the validation group, 42.2% (196/465) patients could be ruled-out. The incidence of MACE within 30 days for ruled-out patients aged >70 years using the established cutoff was 0.Conclusion:The diagnostic performance for the ruled-out and ruled-in diagnosis using the guideline-recommended 0-2 h hs-cTnT cutoff are relatively consistent across different age groups, but the ruled-out rate for patients aged >70 years is lower than for those aged ≤60 and >60-70 years. The ruled-out cutoff established in this study can be used to improve diagnostic performance of thus indicator on suspected NSTEMI patients.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To detect the expression level of serum LncRNA P53RRA in patients with primary hepatocellular carcinoma(HCC)and explore its clinical application value in the diagnosis of HCC.Methods Ninety-three patients with primary HCC visited Zhongshan Hospital Affiliated to Fudan University from November 2019 to December 2020 were selected as the HCC group and 88 healthy individuals undergone physical examination as the control group.Their serum samples were collected and the expression levels of serum LncRNA P53RRA were detected by real-time fluorescence quantitative PCR(qRT-PCR).The correlations of serum P53RRA levels with clinicopathological parameters and clinical biochemical indicators such as alanine aminotransferase(ALT),glutamate amin-otransferase(AST),gamma-glutamyl transpeptidase(GGT),and alkaline phosphatase(ALP)in HCC patients were analyzed.The diagnostic value of serum P53RRA for HCC was evaluated by the receiver operating characteristic(ROC)curve.Results The expres-sion levels of serum P53RRA in HCC patients(2.15±0.22)were significantly lower than that in healthy controls(3.54±0.33),and the difference was statistically significant(t=3.489,P＜0.05).The analysis of clinicopathological parameters showed that the expres-sion levels of serum P53RRA in HCC patients were correlated with tumor staging(χ2=9.590,P＜0.05),α-fetoprotein(AFP,χ2=5.732,P＜0.05),and GGT(χ2=5.732,P＜0.05).ROC curve analysis showed that the area under the ROC curve(AUCROC)of ser-um P53RRA in the diagnosis of HCC was 0.750(95%CI:0.679-0.821),with a sensitivity of 65.6%and specificity of 64.8%.The AUCROC,sensitivity and specificity of P53RRA combined with AFP and GGT in the diagnosis of HCC were 0.911(95%CI:0.867-0.953),88.2%and 70.5%,respectively,which were higher than those of single indicator.Conclusion LncRNA P53RRA is expec-ted to serve as a novel non-invasive biomarker,effectively assisting in the clinical diagnosis of HCC.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective To explore the use of indirect methods to establish a reference interval for serum car-bohydrate antigen 242(CA242)in adults in Shanghai and to validate it.Methods A total of 51 897 cases of CA242 testing data from the laboratory information management system of the Department of Clinical Labo-ratory at the hospital from August 2022 to July 2023 were collected.After data cleaning and normal transfor-mation,the Turkey method was used to remove outliers,and 19 653 cases of data were finally included in the study.Then,the Hoffmann method was used to establish the P95 reference interval for serum CA242.The study selected 691 apparently healthy individuals from January to March 2024 to validate the self built refer-ence interval for CA242.The physical examination population with the reference interval recommended by the reagent instructions≤CA242 value

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*