OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To identify disulfidptosis-related gene(DRG)in acute myocardial infarction(AMI)by bioinformatics,analyze the molecular pattern of DRGs in AMI,and construct a DRGs-related prediction model.Methods AMI-related datasets were downloaded from the Gene Expression Omnibus database,and DRGs with differential expression were screened in AMI.CIBERSORT method was used to analyze the immune infiltration.Based on the differentially expressed DRGs,the AMI patients were classified into distinct subtypes via consensus clustering,followed by immune infiltration analysis,differential expression analysis,gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis,and gene set variation analysis.Weighted gene co-expression network analysis(WGCNA)was then performed to construct subtype-associated modules and identify hub genes.Finally,least absolute shrinkage and selection operator,random forest,and support vector machine-recursive feature elimination were used to screen feature genes to construct a DRGs-related prediction model.The model's diagnostic efficacy was evaluated by nomogram and receiver operating characteristic(ROC)curve analysis,followed by external validation.Results Nine differentially expressed DRGs were identified between AMI patients and controls.Based on the expression levels of these nine DRGs,AMI patients were divided into two DRGs subtypes,C1 and C2.Increased infiltration of monocytes,M0 macrophages,and neutrophils was observed in AMI patients and C1 subtype(all P<0.05),indicating a close correlation between DRGs and immune cells.There were 257 differentially expressed genes between the C1 and C2 subtypes,which were related to biological processes such as myeloid leukocyte activation and positive regulation of cytokines.Fcγ receptor-mediated phagocytosis and NOD-like receptor signaling pathway activity were enhanced in C1 subtype.WGCNA analysis suggested that the brown module exhibited the strongest correlation with DRG subtypes(r=0.67),from which 23 differentially expressed genes were identified.The feature genes screened by three machine learning methods were interpolated to obtain a DRGs-related prediction model consisting of three genes(AQP9,F5 and PYGL).Nomogram and ROC curves(AUC_train=0.891,AUC_test=0.840)showed good diagnostic efficacy.Conclusions DRGs were closely related to the occurrence and progression of AMI.The DRGs-related prediction model consisting of AQP9,F5 and PYGL may provide targets for the diagnosis and personalized treatment of AMI.
Humans ; Myocardial Infarction/diagnosis* ; Transcriptome ; Computational Biology ; Gene Expression Profiling ; ROC Curve ; Gene Regulatory Networks ; Nomograms ; Disulfidptosis

Objective To observe the value of prenatal ultrasound measuring fetal cauda equina nerve parameters for diagnosing tethered cord syndrome(TCS).Methods Forty six fetuses with TCS(TCS group)and 591 healthy fetuses(control group)were retrospectively enrolled.The length,area and angle of cauda equina nerve were measured with prenatal ultrasound and compared between groups,and the value for diagnosing TCS was analyzed.Results Significant differences of the length,area and angle of fetal cauda equina nerve were found between groups(all P＜0.05),with the area under the curve for diagnosing TCS of 0.924,0.809 and 0.972,respectively.Conclusion Prenatal ultrasound measuring fetal cauda equina nerve parameters had high value for diagnosing TCS.

Objective To explore the medication rules of Professor HUANG Li for the treatment of recurrent angina pectoris after percutaneous coronary intervention(PCI)for coronary heart disease by data mining method.Methods The prescriptions for effective cases of recurrent angina pectoris after PCI for coronary heart disease treated by Professor HUANG Li in the outpatient department of China-Japan Friendship Hospital were collected.SPSS Statistics 26.0 software and SPSS Modeler 18.0 software were used for frequency statistics,analysis of the therapeutic actions,properties,flavors and meridian tropism of the prescribed herbs as well as association rule analysis,cluster analysis and factor analysis of the herbs.Results A total of 344 Chinese medicine prescriptions were obtained,involving 209 herbs,with a cumulative frequency of 5 874 times.The top 30 Chinese medicinals were named as the high-frequency Chinese medicines,and the herbs with the frequency over 100 times in descending order were Astragali Radix,Chuanxiong Rhizoma,Puerariae Lobatae Radix,Rhodiolae Crenulatae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Poria,Dalbergiae Odoriferae Lignum,Atractylodis Macrocephalae Rhizoma,Curcumae Rhizoma,Sparganii Rhizoma,Dioscoreae Rhizoma,Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum,Codonopsis Radix,and Glycyrrhizae Radix et Rhizoma.The high-frequency Chinese medicinals were mostly classified as blood-activating and stasis-resolving drugs and qi-replenishing drugs.The medicinal properties of the drugs were characterized by being warm,mild,or cold,the flavors were predominated by being sweet,pungent or bitter,and the medicinals usually had the meridian tropism of the spleen,lung and liver meridians.A total of 30 association rules were mined out,cluster analysis yielded 5 herbal groups,and factor analysis yielded 11 groups of common factors.Conclusion For the treatment of cardiovascular diseases,Professor HUANG Li follows the theory of qi,blood and water,and especially pays more attention to the ascending and descending of qi movement.For qi deficiency and blood stasis contribute to the basic pathogenesis of recurrent angina pectoris after PCI,the therapy of benefiting qi,activating blood and removing stasis is recommended.Moreover,the simultaneous regulation of five zang-organs and simultaneous use of the cold and warm herbs are performed,and the herbs of benefiting qi and invigorating spleen,resolving phlegm and inducing diuresis,tranquilizing mind,promoting qi and dissipating masses,and activating blood to eliminate stasis are used for adjuvant therapy.

Objective To investigate the CT and MRI features of intraosseous myofibroma/myofibromatosis in pediatric patients.Methods The retrospective analysis involved the examination of clinical data and imaging findings from 15 children who were diagnosed with myofibroma/myofibromatosis of bone invasion through pathological means.Subsequently,the imaging characteristics were summarized.Results CT examinations were conducted on a total of 15 patients,with 2 of them also received enhanced scans.Additionally,MRI examinations were conducted on 5 patients,with 3 of them also underwent enhanced scans.Eleven patients were diagnosed with solitary type myofibroma,with 7 cases localized in the skull and the remaining lesions observed in the maxillofacial bone.Three patients exhibited the multicentric type without any involvement of visceral organs,while one patient presented with the multicentric type accompanied by visceral involvement.The lesions exhibited a uniform soft-tissue density on plain CT scan,predominantly located between the inner and outer layers of the bone.Additionally,they displayed swelling changes and osteolytic bone destruction,with some lesions showed residual bone shell.On MRI,the lesions exhibited a uniform signal,demonstrated an isointense or slightly hypointense signal on T1WI and an isointense or slightly hyperintense signal on T2WI.The lesions displayed significantly heterogeneous enhancement on CT and MRI.Conclusion The imaging manifestations of intraosseous myofibroma/myofibromatosis in pediatric patients exhibit certain characteristics,and the residual bone shell in the lesion is helpful for diagnosis,however,distinguishing it from Langerhans cell histiocytosis of the bone remains challenging,necessitating the reliance on pathological diagnosis.

ObjectiveTo reveal the molecular pathogenesis of Hunter syndrome in three families in southern China and to clarify the correlation between phenotype and genotype， so as to lay a foundation for future prenatal or preimplantation genetic diagnosis. MethodsOn the basis of initial clinical diagnosis and pedigree analysis， qualitative detection of glycosaminoglycans in urine was performed first， and then anticoagulant blood samples were collected from the children and their relatives. DNA was extracted and the IDS gene sequence was analyzed by PCR and Sanger sequencing. Various methods such as RT-PCR and bioinformatics analysis were used to identify the pathogenicity of the new variants. ResultsThe urine test results of the patients in the three families were all strongly positive（++）. Probands were all male， with hemizygous mutations in IDS gene from their mothers， and the mutation sites were c.615_622delCATACAGT， c.847_848delGT and IVS7 ds+1 G>A， respectively. The cross-species conservation analysis showed that the amino acid of IDS gene mutation site was highly conserved during species evolution. Compared with the normal protein， mutant proteins exhibited significant differences in the predicted results of advanced structure. The variants identified in the three families were classified as pathogenic by ACMG criteria. ConclusionsThe three probands were diagnosed with Hunter syndrome. The c.615_622del（p.Il206Valfs*18）， c.847_848del（p.Val283Alafs*57） and IVS7 ds+1 G>A （p.G336Dfs*12） of IDS gene are all novel pathogenic mutations， which are the underlying causes of morbidity in children. This study has further enriched the mutation spectrum of IDS gene.

Objective: To explore the changing characteristics of Wnt2/β⁃catenin pathway in liver regeneration and repair in C57BL/6 mice. Methods : Male C57BL/6 mice were randomly divided into a sham⁃operated group (Sham group) , 1 d post⁃operative group , 2 d post⁃operative group , 4 d post⁃operative group , 6 d post⁃operative group , and 8 d post⁃operative group. Mice in the operated group underwent partial hepatectomy ( PHx) to remove the left and middle lobes of the liver, respectively. Plasma and liver tissues were collected on postoperative days 1 , 2 ,4 ,6 , and 8 , and plasma ALT and AST activity was measured by ALT(alanine aminotransferase) and AST( aspartate aminotransferase) biochemical analysis kits; Ki67 ⁃positive cells were identified by immunohistochemistry in each group;the number of HNF4⁃α and Ki67 double positive cells , the number of LYVE1 and Ki67 double positive cells , and the number of β ⁃catenin transferred into the nucleus were determined by immunofluorescence method. The expression of Wnt2 protein in each group was detected by Western blot , and the time characteristics of its expression during liver regeneration were analyzed. Results: Liver weight and liver/body weight ratio peaked on day 6 after PHx and approached the level of the Sham group. After PHx , there was severe liver damage on day 1 , but it had normalized by day 4. On day 2 after PHx , mainly hepatocytes proliferated;and on days 4 and 6 , mainly liver sinusoidal endothelial cells proliferated ,while the Wnt2/β⁃catenin pathway was activated. Conclusion The liver has a powerful regenerative repair ability ,which is closely related to the rapid proliferation of hepatocytes and liver sinusoidal endothelial cells , and the activation of the Wnt2/β⁃catenin pathway is activated in the regenerative repair of the mouse liver.

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

ObjectiveTo explore the value of plasma free metanephrines， including metanephrine（MN） and normetanephrine（NMN）， collectively referred to as MNs in the diagnosis of pheochromocytoma and paraganglioma （PPGL）. MethodsThe study included 1 631 patients suspected of PPGL from December 2014 to December 2020 in SunYat-sen Memorial Hospital. In these subjects， Plasma free MNs were measured by liquid chromatography-tandem mass spectrometry（LC-MS/MS） before surgery. Receiver operating characteristic （ROC） curves were used to determine the sensitivity and specificity of plasma NMN and MN in the diagnosis of PPGL. ResultsOf the screened patients， 108 patients had pathologically confirmed PPGL and 1 523 patients had definitive diagnoses other than PPGL as a control group. The median value of plasma MN ［0.54（0.17~4.48） nmol/L vs. 0.15（0.11~0.21） nmol/L， P<0.001］ and NMN ［7.48（2.12~15.01） nmol/L vs. 0.32（0.22~0.46） nmol/L， P<0.001］ were significant higher in the PPGL group than in the control group. Using an upper cut-off of 0.395 nmol/L for MN， the sensitivity was 60.2% and the specificity was 97.8%； when using a cut-off of 1.105 nmol/L for NMN， the diagnostic sensitivity was 87.0%， and the specificity was 98.7%. The area under the ROC curve and 95% confidence interval of plasma MN and NMN combined were 0.800（0.743， 0.858）， 0.959（0.932， 0.98） and 0.970（0.944， 0.996）， respectively. Analyzing the false-positive results， it was found that in the control group， 3% of the false-positive cases appeared. The estimated glomerular filtration rate（eGFR） were significantly lower in the false-positive group than in the true-negative group ［74.42（51.04~96.96） mL/min vs. 88.51（72.80~101.83） mL/min， P=0.001］. In 212 patients with eGFR lower than 60 mL/min， the false positive rate was increased to 8%. If the upper limit of the reference interval was increased by 25%， the specificity was increased to 96.7%； when the upper limit of the reference interval was increased by 50%， the specificity was 98.6 %. ConclusionsPlasma free MNs has a great reliability in the diagnosis of PPGL. The negative predictive value is extremely high and close to 100%. Combination analysis of plasma MN and NMN can further improve diagnostic performance. However， a few false positive cases may appear and might be influenced by impaired renal function. In patients with eGFR lower than 60 mL/min， the false positive rate is significantly increasing， which need a 25%-50% increase in the expected upper limit of a reference range to guarantee high specificity.