OBJECTIVE: To explore prevalence, incidence and possible factors of immediate herniated discs after posterior cervical expansive open-door laminoplasty (EODL). METHODS: Totally 29 patients with cervical spinal stenosis and intervertebral disc herniation who underwent EODL from October 2020 to December 2021 were collected, including 24 males and 5 females, aged from 43 to 81 years old with an average of (61.3±9.0) years old;the courses of disease ranged from 1 to 120 months with an average of (36.4±37.0) months. Three or more intervertebral discs on C₃-C₇ were observed. The clinical efficacy was evaluated according to Japanese Orthopaedic Association (JOA) score before operation, 3 days and 1, 3, 6 and 12 months after operation, respectively. The changes of herniated disc before and after operation were measured by multipoint area method and two-dimensional distance method, and incidence and percentage of herniated disc regression were further calculated. Cervical imaging parameters such as Cobb angle (C₃-C₇), intervertebral angle, T₁ slope (T₁S), spinal canal sagittal diameter, K-line angle, dural sac sagittal diameter were measured and compared before and after operation. Pearson correlation was used to analyze correlation between cervical sagittal imaging parameters and disc herniation changes before and after operation. RESULTS: All patients obtained grade A wound healing, and 14 of them were followed up for 3(1.00, 5.25) months. There were no immediate or long-term postoperative complications. Totally 101 herniated intervertebral discs were measured, of which 79 regression numbers were obtained by area measurement. The number of intervertebral disc regressions by distance measurement was 77. There was no statistically significant difference in Cobb angle, intervertebral angle, T₁S and K-line angle of C₃-C₇ (P>0.05), however, there were statistically significant differences in sagittal diameter of spinal canal, sagittal diameter of dural sac, and JOA score before and after operation(P<0.05). The regression ratio of disc herniation ranged from 5% to 50%, and regression ratio of disc herniation was greater than 25% in 45.57%(36/79). Disc herniation in C_4,5 was positively correlated with sagittal plane diameter in C₅(r=0.423, P=0.028). There was a negative correlation between changes of C_3,4 and C_3,4 intervertebral angle (r=-0.450, P=0.041). The improvement rate of cervical JOA score immediately after operation was (59.54±15.07) %, and postoperative follow-up improved to (76.57±14.66) %. CONCLUSION Herniated disc regression immediately after EODL is a common occurrence, and EODL should be selected as far as possible under the premise of satisfying surgical indications. The regression of disc herniation is positively correlated with spinal canal sagittal diameter, and spinal canal should be enlarged as far as possible in the appropriate scope during EODL, so as to create more opportunities and conditions for disc regression and achieve better clinical results.
Humans ; Female ; Male ; Intervertebral Disc Displacement/diagnostic imaging* ; Spinal Stenosis/diagnostic imaging* ; Laminoplasty/methods* ; Middle Aged ; Aged ; Cervical Vertebrae/diagnostic imaging* ; Adult ; Aged, 80 and over ; Intervertebral Disc/surgery*

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

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

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 analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective To establish a ultra-high performance liquid chromatography-tandem mass spectrometer(UPLC-MS/MS)method for determining the concentration of sotagliflozin in rat plasma and apply it to pharmacokinetic studies in rats.Methods Electrospray negative ion multi-reaction ion detection was used.Chromatographic column:EXT-C18(2.1 mm × 100.0 mm,2.7 μm);column temperature:45 ℃;mobile phase:5 mmol·L-1 ammonium acetate aqueous solution-acetonitrile;flow rate:0.35 mL·min-1;ion pairs:sotagliflozin m/z 483.3→315.1,dapagliflozin m/z 467.4→329.2;injection volume:6 μL,plasma samples were processed using methyl tert-butyl ether liquid-liquid extraction.Six male SD rats were administered a single oral dose of sogliflozin at 40 mg·kg-1,and detected the concentration of sogliflozin in plasma.Pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.1.1.Results Sotagliflozin showed good linearity within the range of 5-2 000 ng·mL-1,with intra-day and inter-day precision both less than 15％.The recovery rate,matrix effect,and stability were all within the specified range.Pharmacokinetic parameters:Cmax was(3 716.67±568.28)ng·mL-1,tmax was(1.00±0.32)h,t1/2 was(2.28±0.45)h,AUC0-t was(1.70 × 104±2 075.87)ng·mL-1·h.Conclusion This study established a method for determining the concentration of sotagliflozin in rat plasma,which is characterized by high sensitivity,rapid detection,and good repeatability.It is suitable for the determination of sotagliflozin concentration in plasma and pharmacokinetic studies.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.