IgG4-related disease （IgG4-RD） is an idiopathic fibroinflammatory condition characterized by a predilection for tumor-forming lesions， an increase in the serum level of IgG4， excessive infiltration of IgG4-positive plasma cells， storiform fibrosis， and/or obliterative phlebitis. This article reports a rare case of IgG4-RD in which the patient developed recurrent transient ischemic attacks （TIA） after the diagnosis of IgG4-RD. This report explores the potential pathological mechanisms， clinical features， treatment， and prognosis of IgG4-RD with TIA， in order to enhance the awareness of the possible neurological complications associated with IgG4-R among clinicians.
Glucocorticoids

Objective:To investigate the function and mechanism of exosome Linc00665 in modulating CD8+T cell immunoreactivity to promote radiotherapy resistance in OSCC.Methods:HOEC,SCC9 and SCC9-RR exosomes were extracted and identified,and the expression of Linc00665 was detected by qRT-PCR in cell lines and exosomes.The expression of TNF-α,IFN-γ,perforin and granzyme B in each treatment group was detected by ELISA(PBS,SCC9 exo,SCC9-RR exo).The killing ability of CD8+T cells against SCC9 cells in each treatment group was detected by CCK-8 assay.The targets of Linc00665 were further bioinformatically ana-lyzed and verified by qRT-PCR and Western blot.The expression of Linc00665,miR-28-5p and PD-1 in CD8+T cells was exogenous-ly regulated,the expression of immunoreactive factors in the supernatants of each treatment group was detected by ELISA(NC,sh-Linc00665,miR-28-5p inhibitor,sh-PD-1),and the killing ability of cells in each group was detected by CCK-8 method.Results:The concentrations of TNF-α,IFN-γ,perforin and granzyme B in the supernatants of cell culture in the SCC9-RR exo/CD8+T group were significantly decreased compared with those in the PBS/CD8+T group and the SCC9 exo/CD8+T group(P＜0.05),and the kill-ing ability of the cells in the SCC9-RR exo group was significantly decreased compared with those in the PBS group and the SCC9 exo group(P＜0.05),suggesting that SCC9-RR exo could inhibit the tumor killing ability of CD8+T cells.qRT-PCR results suggested that Linc00665 was highly expressed in the SCC9-RR cell line as well as exosome(P＜0.05).It was further verified by bioinformat-ics analysis that Linc00665 could regulate PD-1 expression via miR-28-5p,thereby modulating CD8+T cell immunoreactivity to pro-mote OSCC radiotherapy resistance.Conclusion:Exosome Linc00665 regulates CD8+T cell immunoreactivity through miR-28-5p/PD-1 axis to promote OSCC radiotherapy resistance.

Objective To achieve non-invasive and precise prediction of mean arterial pressure(MAP)based on a fully convolutional neural network(FCNN).Methods A high-precision blood pressure data acquisition system compliant with international metrological standards was used in conjunction with the'gold standard'auscultation method to collect blood pressure and pulse waveform data from patients.True MAP values were derived via Gaussian fitting of pulse waveform data,constructing a traceable dataset.The FCNN was applied to this dataset to develop a novel MAP prediction method.Additionally,the predictive accuracy of the FCNN was compared with linear regression and conventional empirical formulas.Results The mean squared errors(MSE)for MAP prediction using the FCNN,linear regression,and empirical formulas were 19.76,21.40,and 30.97,respectively.The coefficients of determination(R2)were 0.90,0.89,and 0.84,and the prediction accuracies were 0.90,0.89,and 0.85,respectively.Conclusions By using systolic blood pressure,diastolic blood pressure,age,and arm circumference as input parameters,the FCNN-based MAP prediction method significantly reduces the bias of empirical formulas.This approach not only improves the accuracy of hemodynamic boundary condition acquisition but also contributes to refining the metrological traceability system of non-invasive blood pressure measurement.

Objective To achieve non-invasive and precise prediction of mean arterial pressure(MAP)based on a fully convolutional neural network(FCNN).Methods A high-precision blood pressure data acquisition system compliant with international metrological standards was used in conjunction with the'gold standard'auscultation method to collect blood pressure and pulse waveform data from patients.True MAP values were derived via Gaussian fitting of pulse waveform data,constructing a traceable dataset.The FCNN was applied to this dataset to develop a novel MAP prediction method.Additionally,the predictive accuracy of the FCNN was compared with linear regression and conventional empirical formulas.Results The mean squared errors(MSE)for MAP prediction using the FCNN,linear regression,and empirical formulas were 19.76,21.40,and 30.97,respectively.The coefficients of determination(R2)were 0.90,0.89,and 0.84,and the prediction accuracies were 0.90,0.89,and 0.85,respectively.Conclusions By using systolic blood pressure,diastolic blood pressure,age,and arm circumference as input parameters,the FCNN-based MAP prediction method significantly reduces the bias of empirical formulas.This approach not only improves the accuracy of hemodynamic boundary condition acquisition but also contributes to refining the metrological traceability system of non-invasive blood pressure measurement.

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 investigate the function and mechanism of exosome Linc00665 in modulating CD8+T cell immunoreactivity to promote radiotherapy resistance in OSCC.Methods:HOEC,SCC9 and SCC9-RR exosomes were extracted and identified,and the expression of Linc00665 was detected by qRT-PCR in cell lines and exosomes.The expression of TNF-α,IFN-γ,perforin and granzyme B in each treatment group was detected by ELISA(PBS,SCC9 exo,SCC9-RR exo).The killing ability of CD8+T cells against SCC9 cells in each treatment group was detected by CCK-8 assay.The targets of Linc00665 were further bioinformatically ana-lyzed and verified by qRT-PCR and Western blot.The expression of Linc00665,miR-28-5p and PD-1 in CD8+T cells was exogenous-ly regulated,the expression of immunoreactive factors in the supernatants of each treatment group was detected by ELISA(NC,sh-Linc00665,miR-28-5p inhibitor,sh-PD-1),and the killing ability of cells in each group was detected by CCK-8 method.Results:The concentrations of TNF-α,IFN-γ,perforin and granzyme B in the supernatants of cell culture in the SCC9-RR exo/CD8+T group were significantly decreased compared with those in the PBS/CD8+T group and the SCC9 exo/CD8+T group(P＜0.05),and the kill-ing ability of the cells in the SCC9-RR exo group was significantly decreased compared with those in the PBS group and the SCC9 exo group(P＜0.05),suggesting that SCC9-RR exo could inhibit the tumor killing ability of CD8+T cells.qRT-PCR results suggested that Linc00665 was highly expressed in the SCC9-RR cell line as well as exosome(P＜0.05).It was further verified by bioinformat-ics analysis that Linc00665 could regulate PD-1 expression via miR-28-5p,thereby modulating CD8+T cell immunoreactivity to pro-mote OSCC radiotherapy resistance.Conclusion:Exosome Linc00665 regulates CD8+T cell immunoreactivity through miR-28-5p/PD-1 axis to promote OSCC radiotherapy resistance.

The 2024 update of the Lancet Commission on Dementia synthesizes new research findings since the 2020 report, presenting promising evidence for the prevention, intervention, and care of dementia.This paper explored the key elements of risk factor management as delineated in the report.Currently recognized risk factors associated with cognitive impairment include less education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury, social isolation, and air pollution.Furthermore, the updated report identifies vision loss and elevated LDL cholesterol as significant contributors to cognitive decline.This article reviewed the most recent evidence-based findings and examines potential underlying mechanisms related to these 14 identified risk factors.It aims to extract strategies for preventing cognitive impairment and proposes a life-course model for managing these risks.Theoretically, addressing these 14 risk factors could avert up to 45% of dementia cases.The paper concluded with forward-looking recommendations for the effective management of cognitive impairment risk factors and outlines directions for future research.

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.

Cytochrome P450 (CYP450) enzymes, as versatile biocatalysts with the broadest range of catalytic reactions in nature, play critical roles in the metabolism of medicinal plants. They are involved in various oxidative modification processes of active ingredients, facilitating both the synthesis and degradation of bioactive substances. This review delves into the classification, structure, and catalytic mechanisms of CYP450 enzymes, emphasizing their indispensable roles in plant biosynthesis. Using representative cases, including the biosynthetic pathways of tanshinones, artemisinin, celastrol, paclitaxel, and berberine, this review highlights the functional importance of specific CYP450s. For instance, CYP71AV1 catalyzes the production of artemisinin and artemisinic aldehyde, with its activity directly affecting artemisinin yield. Similarly, CYP76AH1 and CYP76AK1 play pivotal roles in the backbone construction and postmodification of tanshinones, acting as key players in their metabolic network. In the case of celastrol, CYP712K1, CYP712K2, and CYP712K3 initiate the first oxidative reaction, providing a solid foundation for subsequent biosynthetic processes. These examples highlight the pivotal role of CYP450 enzymes in the biosynthesis of medicinal plants, showcasing both their complexity and significance in plant metabolic pathways. Furthermore, this review examines the oxidative metabolism of CYP450 enzymes under aerobic conditions and their reductive metabolism in specific environments, offering deeper insights into their catalytic mechanisms. A comprehensive understanding of these processes lays the groundwork for the effective application of CYP450 enzymes in biotechnology and plant metabolic engineering.

Objective To investigate the influencing factor of prognosis of symptomatic intracranial large artery occlusive(ILAO)cerebral infarction in nonacute phase.Methods According to the prognosis,86 patients with symptomatic ILAO cerebral infarction in nonacute phase were divided into good prognosis group and poor prognosis group,and the clinical data of the two groups were compared.Multifactorial Logistic regression analysis was used to screen out the factors that influence prognosis.The related factors were combined to construct a nomogram for predicting poor prognosis of ILAO cerebral infarction in nonacute phase,validated by calibration curves and decision curve analysis.Results Compared with those in the good prognosis group,age,admission mRS,admission NIHSS score,globulin level and medication ratio in the poor prognosis group were significantly higher,and triacylglycerol level,albumin-globulin ratio in the poor prognosis group were significantly lower(P＜0.05-0.01).Multifactorial Logistic regression analysis showed that admission mRS was positively associated with poor 3-month prognosis of patients with ILAO cerebral infarction in nonacute phase(OR=2.551,95％CI:1.134-5.738,P=0.024);endovascular opening therapy was negatively associated with poor 3-month prognosis of patients with ILAO cerebral infarction in the nonacute phase(OR=0.132,95％CI:0.027-0.634,P=0.011).Incorporating admission mRS and endovascular opening treatment to establish a nomogram had good predictive efficacy.Conclusions Admission mRS and endovascular recanalization treatment increased and decreased the risk of poor prognosis at 3 months in patients with ILAO cerebral infarction in nonacute phase,respectively.The nomogram established by combining the two has good application value in predicting the poor prognosis of patients.