Objective To explore macrophage subpopulations in ischemic stroke (IS) by using single-cell RNA sequencing (scRNA-seq) data analysis and High-Dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA). Methods Based on single-cell sequencing data, transcriptomic information for different cell types was obtained, and macrophages were selected for subpopulation identification. hdWGCNA, cell-cell communication, and pseudotime trajectory analysis were used to explore the characteristics of macrophage subpopulations following IS. Key genes related to IS were identified using microarray data and validated for diagnostic potential through Receiver Operating Characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential functions of these genes. Results The scRNA-seq data analysis revealed significant changes in macrophage subpopulation composition after IS. A specific macrophage subpopulation enriched in the stroke group was identified and designated as MCAO-specific macrophages (MSM). Pseudotime trajectory analysis indicated that MSM cells were in an intermediate stage of macrophage differentiation. Cell-cell communication analysis uncovered complex interactions between MSM cells and other cells, with the CCL6-CCR1 signaling axis potentially playing a crucial role in neuroinflammation. Two gene modules associated with MSM were identified via hdWGCNA, significantly enriched in pathways related to NOD-like receptors and antigen processing. By integrating differentially expressed MSM genes with conventional transcriptomic data, three IS-related hub genes were identified: Arg1, CLEC4D, and CLEC4E. Conclusion This study reveals the characteristics and functions of macrophage subpopulations following IS and identifies three hub genes with potential diagnostic value, providing novel insights into the pathological mechanisms of IS.
Macrophages/metabolism* ; Computational Biology/methods* ; Single-Cell Analysis/methods* ; Transcriptome ; Ischemic Stroke/metabolism* ; Animals ; Gene Regulatory Networks ; Gene Expression Profiling ; Humans ; Male

In recent years,an increasing body of research has reported that the gut microbiota can modulate host immune responses and is associated with a variety of immune-related diseases.The gut microbiota plays a pivotal role in maintaining immune homeostasis.In numerous immune-related inflammatory diseases,significant alterations have been observed in both the gut microbiota and its derived metabolites,short-chain fatty acids(SCFAs).These microbial communities and metabolites play a crucial role in the pathogenesis of immune-related inflammatory diseases such as inflammatory bowel disease,diabetes,rheumatoid arthritis,and systemic lupus erythematosus.In this review,we discuss the latest developments in the human gut microbiome's association with autoimmune diseases(ADs)and the feasibility of developing novel diagnostics based on microbiome profiling.We aim to provide new drug targets for the treatment of autoimmune diseases,thereby paving a way for drug research and development.

Objective To compare the efficacy of double filtration plasmapheresis(DFPP),centrifugal therapeutic plasma exchange(cTPE)and centrifugation-filtration plasmapheresis(CFPP)in improving renal insufficiency after kidney transplantation,as well as the differences in inducing plasma exchange-related adverse reactions.Methods Clinical data from 46 patients who underwent plasma exchange after renal transplantation in our hospital were retrospectively collected,and patiens were divided into DFPP group(n=33),cTPE group(n=7)and CFPP group(n=6).Changes in peripheral blood creatinine,albumin,hemoglobin,platelets,fibrinogen levels and urine volume before and after TPE were compared and analyzed among the three groups.Results Among the DFPP group,cTPE group and CFPP group,the creatinine after TPE decreased by(31.40±25.38)%,(58.91±19.75)%and(39.44±28.64)%,respectively,with cTPE group significant-ly higher than the DFPP group(P＜0.05),but no significant differences between the DFPP group and cTPE group(P＞0.05);the urine volume after TPE increased by(49.33±30.03)%,(54.62±39.32)%and(68.89±23.00)%,showing no significant differences(P＞0.05);the hemoglobin after TPE decreased by(11.97±5.94)%,(20.17±5.75)%and(9.65±8.75)%,respectively,with the cTPE group significantly higher than the DFPP group and CFPP group(P＜0.05),but no significant difference between the DFPP group and CFPP group(P＞0.05).The platelet count after TPE decreased by(37.88±18.39)%,(24.56±12.36)%and(21.40±12.51)%,respectively,with no significant differences between the three groups(P＞0.05);the fibrinogen after TPE decreased by(0.57±0.20)%,(0.14±0.06)%and(0.26±0.22)%,re-spectively,with the DFPP group significantly higher than the cTPE group(P＜0.05),but the CFPP group had no significant difference with cTPE group or DFPP group(P＞0.05);the albumin after TPE decreased by(11.41±5.97)%,(14.67±6.52)%and(25.18±5.10)%,respectively,with cTPE group and DFPP group significantly lower than the CFPP group(P＜0.05,P＜0.001),but with no significant difference between the DFPP group and cTPE group(P＞0.05).Conclusion The effect of three plasma exchange methods varies on renal function,anemia and coagulation function of patients after kid-ney transplantation.It is necessary to consider the the patient's disease characteristics and treatment needs,as well as the laboratory′s technical conditions and plasma supply when selecting TPE methods.

Objective:To explore the influence of multidisciplinary treatment (MDT) on clinical staging and diagnosis and treatment strategies for rectal cancer.Methods:A retrospective case series study was conducted. The clinical data of 142 rectal cancer patients who underwent surgical treatment in Shanxi Provincial People's Hospital from March 2021 to December 2021 were retrospectively analyzed. According to whether to implement MDT or not, all patients were divided into MDT group (68 cases) and non-MDT group (74 cases). Relevant clinical data including patients' basic information (gender, age, etc.), TNM staging, whether to receive neoadjuvant radiotherapy and chemotherapy or not, surgical methods, R0 resection rate of both groups were compared. The implementation methods and the effects of MDT for patients were summarized.Results:There were statistically significant differences in the proportion of clinical N staging at initial diagnosis, whether to receive neoadjuvant radiotherapy and chemotherapy or not of both groups (all P < 0.05). The overall agreement rate of clinical T staging at initial diagnosis and pathological T staging was 67.6% (46/68), 50.0% (37/74), respectively in the MDT group and the non-MDT group, and the difference was statistically significant ( χ2 = 4.54, P = 0.033). The overall agreement rate of N staging at initial diagnosis and pathological N staging was 50.0% (34/68), 54.1% (40/74), respectively in the MDT group and the non-MDT group, and the difference was not statistically significant ( χ2 = 0.23, P = 0.629). The treatment rate of neoadjuvant radiotherapy and chemotherapy was 57.4% (39/68) and 4.1% (3/74), respectively in the MDT group and the non-MDT group, and the difference was statistically significant ( χ2 = 48.33, P < 0.001). The R0 resection rate in both the MDT group and non-MDT group was 100.0%, and no tumor tissue was found at the upper, lower, and circumferential margins. Conclusions:MDT could provide more accurate clinical staging and more effective diagnosis and treatment opinions for patients, and provide reliable guidance for the treatment selections.

Objective To conduct a detailed clinical phenotypic analysis and gene mutation detection on an au-tosomal dominant Van der Hoeve syndrome family,and to identify the pathogenic gene mutation sites of the family and the impact of the mutation on gene coding.Methods Clinical data including medical history,physical examina-tion and auxiliary examination were collected and peripheral blood samples were collected from the Van der Hoeve syndrome families.Exome sequencing and Sanger sequencing were performed on 22 family members.The data were analyzed using bioinformatics software.Results The family had a total of 5 generations,with each generation expe-riencing consecutive illnesses.Each generation of men and women could suffer from the disease,which conformed to the characteristics of autosomal dominant inheritance.The 12 patients in this family were all born with blue sclera and short stature.8 patients had a history of fractures and could heal normally.3 patients were considering hearing loss caused by Van der Hoeve syndrome.12 patients had a base deletion(c.1128delT)in exon 17 of the COL1A1 gene,causing a change in the amino acid coding after position 376 and ending the amino acid coding prematurely at position 539.10 asymptomatic individuals in this family didn't had this mutation.Conclusion The patient of this family was identified as Van der Hoeve syndrome caused by c.1128 delT mutation.

Due to the fact that the articular cartilage of children's joints has not yet been fully ossified, visualizing the adjacent anatomical structures during the clinical diagnosis and treatment of joint diseases and injuries in children is a challenging issue. Arthrography is an efficient, convenient, and minimally invasive technique, and is particularly crucial for the visualization of children's hip joints. Currently, arthrography technology is widely employed during surgeries for developmental dysplasia of the hip (DDH), and in recent years, numerous studies have concentrated on the efficacy of joint angiography, exploring its assessment and predictive roles during and after the operation. We review the overview of hip joint arthrography techniques, such as the concept of arthrography, the selection of access routes for hip joint arthrography, the process of hip joint arthrography, the dosage and operation of contrast agents, and the adverse reactions of contrast agents; the use of hip joint arthrography to evaluate the quality of closed reduction; the use of hip joint arthrography to predict the future development and outcome of the acetabulum after closed reduction; the use of hip joint arthrography in the study of open reduction or osteotomy; the use of hip joint arthrography to observe the morphology of soft tissues in the hip joint; the use of hip joint arthrography in combination with nuclear magnetic resonance to observe the anatomical structure of the acetabular labrum. Summarizing the research results of arthrography for evaluating the corresponding indicators of the hip joint helps improve the matching between the femoral head and the acetabulum and the accuracy of evaluating the quality of reduction, uncovers identifying factors such as labrum varus that hinder concentric reduction, enhances the ability to predict the development and outcome of the acetabulum, and has significant guiding significance for the precise selection of the timing of surgical intervention for early and residual deformities in children with DDH. Exploring the application of arthrography technology in evaluating the quality of closed reduction in DDH and predicting the development of the acetabulum after reduction is expected to provide meaningful references for orthopedic surgeons in the current clinical diagnosis, treatment, and research of DDH.

Objective To systematically evaluate the efficacy and safety of dronedarone in preventing early recurrence of atrial fibrillation(AF)after ablation.Methods PubMed,Web of Science,Cochrane Library,Embase,CNKI,WanFang Data and VIP databases were electronically searched to collect the clinical studies on the efficacy and safety of dronedarone in preventing early recurrence of AF after ablation from the inception to April 16,2024.Two researchers independently screened the literature,extracted data,and assessed the risk of bias of the included studies.Meta-analysis was performed by using RevMan 5.3 software.Results A total of three randomized controlled trials and eight cohort studies were ultimately included,including 1 534 patients.The results of meta-analysis showed that there was no statistically significant difference in the early recurrence rate of AF after ablation between the dronedarone group and the amiodarone group(RR=1.15,95％CI 0.90 to 1.47,P=0.25).Compared with the amiodarone group,the dronedarone group had a higher incidence of bleeding(RR=2.28,95％CI 1.08 to 4.81,P＜0.05),a higher incidence of gastrointestinal adverse reactions(RR=3.87,95％CI 1.39 to 10.74,P=0.009)and a lower incidence of thyroid dysfunction(RR=0.15,95％CI 0.06 to 0.40,P＜0.001).There was no statistically significant difference in the incidence of postoperative bradycardia,liver and kidney dysfunction,and total adverse drug reactions between the two groups(P＞0.05).Compared with the propafenone group,the dronedarone group had a lower early recurrence rate of AF after ablation(RR=0.31,95％CI 0.17 to 0.57,P＜0.001).However,there was no statistically significant difference in the incidence of adverse reactions between them(P＞0.05).Conclusion Current evidence suggests that dronedarone is as effective in preventing early recurrence after AF ablation as amiodarone,but more effective than propafenone.In terms of safety,compared to amiodarone,dronedarone has a lower risk of thyroid dysfunction,but a higher risk of gastrointestinal adverse reactions and bleeding.Due to the limited quality and quantity of the included studies,more large sample,multi-center and high-quality studies are needed to verify the above conclusion.

In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Cocrystal separation technology is a technology that utilizes coformers to selectively form cocrystals with target compounds and separate them from mixed systems. Our study used puerarin (PUE), daidzein (DDZ), and genistein (GEN) as model drugs, which have similar structures and are the main isoflavones in Pueraria lobata root. The separation and purification processes in the modern traditional Chinese medicine (TCM) of these three components use conventional column chromatography, recrystallization, and other technologies, which have the issues of lengthy separation cycles, high solvent consumption, and inefficient preparation. Different with existing separation technology, our team used the early-found cocrystal separation method to design a step-by-step extraction and separation experiment of GEN-PUE-DDZ ternary mixture. Caffeine and L-proline were added to the mixed system in turn, GEN-caffeine cocrystal and PUE-proline cocrystal were prepared by suspension method. The cocrystals precipitated out of the solution. The purities of the GEN-caffeine cocrystal and the PUE-proline cocrystal could achieve 93% (the purity of GEN) and 99% (the purity of PUE). Besides, the purity of DDZ could also be increased by 6.76 times. This study proposed a simple operating, low cost and wide application range separation method different from the traditional separation method and realized the separation of structurally similar chemical components in TCM, laying a foundation for the application of cocrystal technology in the separation and refining of TCM.