Immune checkpoint inhibitors can induce a rare but fatal complication known as hemophagocytic lymphohistiocytosis(HLH). However, reports of ICI-related HLH in breast cancer are extremely limited, and no cases induced by the combination of toripalimab with chemotherapy have been documented. This article reports a case of a breast cancer patient who developed persistent high fever 13 days after receiving toripalimab combined with chemotherapy. Diagnostic evaluations met the HLH-2004 diagnostic criteria. Following methylprednisolone pulse therapy, the patient's symptoms improved rapidly, with subsequent consolidation treatment involving low-dose etoposide. Follow-up examinations one month after discharge showed normal results. This case suggests that toripalimab may induce HLH in breast cancer patients and that initial treatment with glucocorticoids alone can be effective. It provides a reference for the early clinical identification and management of such severe immune-related adverse events.

In recent years, the spread of clubroot disease caused by Plasmodiophora brassicae infection has seriously affected the yield and quality of Brassica juncea (L.) Czern.. The cascade of mitogen-activated protein kinases (MAPKs), a highly conserved signaling pathway, plays an important role in plant responses to both biotic and abiotic stress conditions. To mine the MAPK genes related to clubroot disease resistance in B. juncea, we conducted a genome-wide analysis on this vegetable, and we analyzed the phylogenetic evolution and gene structure of the MAPK gene family in mustard. The 66 BjuMAPK genes identified by screening the whole genome sequence of B. juncea were unevenly distributed on 17 chromosomes. At the genomic scale, tandem repeats led to an increase in the number of MAPK genes in B. juncea. It was found that members of the same subfamily had similar gene structures, and there were great differences among different subfamilies. These predicted cis-acting elements were related to plant hormones, stress resistance, and plant growth and development. The expression of BjuMAPK02, BjuMAPK15, BjuMAPK17, and BjuMAPK19 were down-regulated or up-regulated in response to P. brassicae infection. The above results lay a theoretical foundation for further studying the functions of BjuMAPK genes in B. juncea in response to the biotic stress caused by clubroot disease.
Mustard Plant/parasitology* ; Plasmodiophorida/pathogenicity* ; Plant Diseases/genetics* ; Mitogen-Activated Protein Kinases/metabolism* ; Phylogeny ; Disease Resistance/genetics* ; Gene Expression Regulation, Plant ; Genome, Plant ; Plant Proteins/genetics*

Secondary metabolites of medicinal plants are extremely important to human health because of their special pharmacological activities or efficacy. They are the main source of drugs, health care products, and cosmetics. As human beings continue to pursue health and longevity, the demand in the pharmaceutical market continues to grow. It becomes especially important to improve the production and quality of secondary metabolites of medicinal plants. Plant secondary metabolites are a kind of adaptation of plants to their environment and are the result of the interaction between plants and biotic and abiotic factors during the long-term evolution process. The production and accumulation of secondary metabolites in medicinal plants are mainly affected by plant genetic factors and environmental factors. Among them, light environment is extremely important for their synthesis. Therefore, light regulation has long been a research focus for many scholars in China and abroad. In this article, we the recent research progress on the effects of light regulation on the secondary metabolites of medicinal plants were reviewed, mainly focusing on the effects of light quality, light intensity and photoperiod, in order to provide theoretical basis and practical guidance for the efficient production of secondary metabolites with important pharmacological activities.

Objective:To investigate the feasibility of a three-dimensional no new U-Net (3D nnU-Net) deep learning (DL) network for the automatic segmentation of colorectal cancer (CRC) based on abdominal CT images.Methods:This was a cross-sectional study. From January 2018 to May 2023, a total of 2180 primary CRC patients, confirmed by pathology at the Guangdong Provincial Hospital of Traditional Chinese Medicine (center 1, n=777), Nanfang Hospital, Southern Medical University (center 2, n=732), and Sun Yat-sen Memorial Hospital (center 3, n=671), were enrolled in this retrospective study. The baseline abdominal CT examination of each patient was conducted using CT equipment from 7 different models across 4 vendors, at the 3 centers, encompassing both the arterial phase (AP) and venous phase (VP). Two radiologists manually delineated the volume of interest to circumscribe the entire tumors in dual-enhanced phase CT images. The CT data of CRC patients from center 1 and center 3 were merged and divided into a training set ( n=1 159) and a validation set ( n=289) using a weighted random method with a ratio of 4∶1. The patients from center 2 were used as an independent external test set ( n=732). The 3D nnU-Net segmentation model was trained and tested. Using manually annotated label data as the benchmark, segmentation performance of the model was evaluated based on different phases and tumor locations. The segmentation coverage rate (SCR), Dice similarity coefficient (DSC), recall (REC), precision (PRE), F1-score, and 95% Hausdorff distance (HD 95) were calculated. The mean manual segmentation time and the mean automatic time were compared using independent samples t-test. Results:In the independent external test set, the performance of the 3D nnU-Net model based on the AP CT images was superior to that based on the VP CT images. On the AP images, the SCR, DSC, REC, PRE, F1-score, and HD 95 were 0.865, 0.714, 0.716, 0.736, 0.714, and 27.228, respectively; on the VP images, they were 0.834, 0.679, 0.710, 0.675, 0.679, and 29.358, respectively. The model achieved the best performance on right-sided colon cancer, with SCR, DSC, REC, PRE, F1-score, and HD95 on the AP CT images at 0.901, 0.775, 0.780, 0.787, 0.775, and 21.793, respectively. Next were left-sided colon cancer and rectal cancer, while the segmentation performance for transverse colon cancer was the worst (SCR, DSC, REC, PRE, F1-score, and HD 95 were 0.731, 0.631, 0.641, 0.630, 0.631 and 38.721, respectively). The automatic segmentation time on a single phase was (1.0±0.3) min, while the manual segmentation time was (17.5±6.0) min ( t=128.24, P<0.001). Conclusions:After training and validating on a dataset from multiple centers with various CT scanner vendors, the 3D nnU-Net DL model demonstrates the capability to automatically segment CRC based on abdominal CT images, while also showcasing commendable robustness and generalization ability.

Objective:To summarize the clinical and genetic characteristics of mental retardation disorder (MRD) with TRIO gene variant in children.Methods:Case series study. The data of 9 children with TRIO gene variants were collected retrospectively from August 2019 to March 2024 in Department of Neurology, Beijing Children′s Hospital, Capital Medical University and Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University. The data included gender, age, intellectual and motor development, appearance, seizures, neuroimaging and genetic results. The clinical features and genotype-phenotype correlations were summarized.Results:Of the 9 children, 6 boys and 3 girls, 4 MRD63 children presented with moderate to severe developmental delays accompanied by macrocephaly; 5 MRD44 children had mild to moderate developmental delays with microcephaly. A total of 5 children had dysmorphic facial features (flat occiput, thick eyebrows, unibrow, large ears, short fingers, pale skin, yellow hair, and strabismus), 2 children experienced seizures (1 child with myoclonic seizure and 1 with absence seizure), 4 children had feeding difficulties, 1 child had congenital cataracts, 1 child had congenital heart disease, 1 child had recurrent infections, and 1 child had tiger-striped changes in the fundus examination. TRIO gene variants carried by the 9 children were all de novo, involving 8 variant sites, including 7 missense variants and 1 frameshift variant, c.3232C>T/p.R1078W (2 cases), c.3920A>G/p.Y1307C, c.4112A>T/p.H1371L, c.4283G>T/p.R1428L, c.4394A>G/p.N1465S, c.6041T>C/p.I2014T, c.6821G>A/p.R2274H, c.7027delC/p.Q2343Sfs*70. Among them, 2 sites are located in the Spectrin domain, 4 sites are in the GEFD1 domain, 2 sites are in the GEFD2 domain, and 1 site (frameshift variant) is in the PH2-SH3 domain. The individual with frameshift variant exhibit absence seizures, mild developmental delay, and the mildest phenotype. The child with myoclonic seizures was treated with valproic acid and levetiracetam for seizure control, while the child with absence epilepsy was treated with valproic acid and lamotrigine for seizure control. All 9 children underwent regular rehabilitation exercises, making slow progress.Conclusions:TRIO gene related MRD is characterized by varying degrees of developmental delay, and often accompanied by macrocephaly or microcephaly, dysmorphic facial features, and with or without seizures. The main variant types are missense variants, which are mostly concentrated in the Spectran domain and GEFD domain. p. R1078W may be a relative hotspot variant. The phenotype caused by the frameshift variant is relatively milder.

With the progressive advance and application of information technology,general artificial intelligence technology is leading the fourth industrial revolution,and opens a new era in terms of changing people's produc-tion,life and learning.The digital age is characterized by more emphasis on the comprehensive cultivation of com-petence,trans-border integration,collaborative communication,innovative consciousness,critical thinking and problem-solving.Data-driven educational transformation is one of the important directions of education reform,in which digital literacy of college teachers is crucial to data-driven educational transformation.From the perspective of data-driven educational transformation enabling the improvement of digital literacy of medical college teachers,the present article analyzed the positive impact on improving the quality and personalization of education as well as pro-fessional capacity building and faculty development to meet the needs of medical education in the new era.

Objective:To explore the effects of the transtheoretical model (TTM) -based intervention in patients undergoing coronary angiography (CAG) .Methods:Totally 146 patients who were scheduled to undergo CAG at Fuwai Central China Cardiovascular Hospital from May 2021 to May 2022 were selected by convenience sampling. Patients admitted from May to November 2021 were assigned to the control group ( n=73), and those admitted from December 2021 to May 2022 were assigned to the observation group ( n=73). The control group received routine care, while the observation group received TTM-based intervention. The effects of the intervention were evaluated using the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), and a self-designed CAG compliance assessment form. Results:After the intervention, SAS and SDS scores decreased in both groups, with the observation group scoring significantly lower than the control group ( P< 0.05). The CAG compliance in the observation group was also significantly higher than that in the control group ( P<0.05) . Conclusions:The TTM-based intervention can improve the psychological state of CAG patients and enhance their compliance with CAG procedures.

Objective:To investigate the correlation between the promoter methylation level of Dickkopf-related protein 1 (DKK1) gene and diabetic microangiopaopathy complicated with osteoporosis.Methods:Patients with type 2 diabetes mellitus (T2DM) microangiopathopathy who were admitted to our hospital from Jan. 2019 to Dec. 2022 were collected as research objects, and divided into observation group (44 cases) and control group (58 cases) according to whether they were complicated with osteoporosis. Bone mineral density (BMD) of lumbar spine (L1-4) was measured, and bone metabolism indexes, including serum calcium, serum phosphorus, 25-hydroxy vitamin D3[25-hydroxy vitamin D3, 25- (OH) D3], PTH, C-terminal telopeptide of typeI collagen (CTX), procollagen of aminoterminal propeptide (PINP) and tartrate resistant acid phosphatase (TRACP) levels were detected; The promoter methylation level of DKK1 gene was determined.Results:The methylation level of DKK1 gene promoter in the observation group was 5.17%±0.73%, which was significantly higher than that in the control group (3.81%±0.61%), with statistical significance ( t=5.22, P<0.001). The 25- (OH) D3 level, PTH and lumbar bone density in the observation group were significantly lower than those in the control group, while the CTX and TRACP levels were significantly higher than those in the control group ( t was 5.58, 4.35, 4.12, 4.05 and 4.17, respectively, P<0.001). In all patients, the promoter methylation level of DKK1 gene was significantly positively correlated with CTX and TRACP ( r was 0.41 and 0.39, P was 0.006 and 0.027, respectively), and significantly negatively correlated with PTH and lumbar bone density ( r was -0.38 and -0.43, respectively). P=0.015 and 0.003, respectively). ROC curve analysis showed that the area under the curve of DKK1 methylation level to distinguish type 2 diabetes microangionopathy with and without osteoporosis was 0.841 (0.762-0.921), and the sensitivity and specificity were 86.4% and 72.4%, respectively. Conclusion:The methylation level of DKK1 gene promoter is associated with osteoporosis and bone metabolism in T2DM patients with microangiopathia.

Objective:To study the application value of refined centralized management combined with scientific preventive maintenance in the standardized management of clinical ventilators.Methods:The ventilator failure information wad collected,a ventilator information management database was established,the refined and centralized management and scientific preventive maintenance measures for ventilators was developed in terms of planning,implementing,and updating the ventilator management system as well as training and assessment.119 ventilators in clinical use in People's Hospital of the Xinjiang Uygur Autonomous Region from 2021 to 2022 were selected,the conventional management mode(referred to as conventional mode,50 units)and the refined centralized management combined with scientific preventive maintenance mode(referred to as joint mode,69 units)were adopted respectively for management.The maintenance status of ventilators in the two modes and the total amount of work in 2021 and 2022 were compared.Results:There were 85 ventilator failures in 2021 and 58 ventilator failures in 2022 in conventional mode.34 ventilator failures in 2021 and 44 ventilator failures in 2022 in joint mode.The number of failures,maintenance time and satisfaction of clinical department with the ventilators of the joint mode in 2021 were(3.25±1.06)times/month,(12.57±10.31)days and(91.50±1.73)% respectively,the number of failures and maintenance time were less than those of conventional mode,satisfaction of clinical department was higher than that of the conventional mode,the difference was statistically significant(t=14.458,2.501,2.563,P<0.05).The number of failures of ventilators of joint mode in 2022 was(3.08±2.02)times/month,which was less than that of conventional mode,the difference was statistically significant(t=4.655,P<0.05).The number of failures,number of times to contact the equipment department,consumable costs,adverse events,and number of terminal disinfections for 119 ventilators of the two modes in 2021 were(10.25±2.34)times/month,(16.75±6.54)times/month,and CNY(44,000±49,300)/month,(2.49±0.92)pieces/month and(382.58±83.67)times/month,which were higher than those in 2022,the equipment completeness rate and frequency of clinical training were(88.27±1.29)% and(3.42±1.51)times/month,respectively,which were lower than those of 2022,the difference was statistically significant(t=5.124,6.103,4.099,7.884,1.980,5.607,3.564,P<0.05).Conclusion:Refined centralized management combined with scientific preventive maintenance can effectively reduce the number of ventilator failures,maintenance time and costs,etc.,and improve the quality of standardized management of clinical ventilators.

Objective To evaluate the value of perfusion imaging mismatch and low perfusion ratio(HIR)based on CT perfusion imaging in predicting acute intracranial large vessel occlusion(LVO)associated with intracranial atherosclerotic stenosis(ICAS).Methods A total of 82 pa-tients with acute intracranial LVO who underwent emergency thrombectomy in our hospital from February 2019 to December 2020 were enrolled in this study.According to the etiology,they were divided into ICAS-related LVO group(ICAS-LVO,65 cases)and cardiogenic embolism group(17 cases).ROC curve was plotted to analyze the predictive value of CT perfusion imaging parame-ters.Results Compared with the cardiogenic embolism group,the ICAS-LVO group had signifi-cantly larger male ratio,higher BMI and TG level,more severe progression of disease,longer time from onset to surgery,larger proportion of ischemic penumbra and higher mismatch ratio,and ob-viously less ratio of atrial fibrillation,lower BNP and HDL levels,smaller infarct volume,and lower HIR(P＜0.05,P＜0.01).ROC curve analysis showed that HIR and mismatch ratio had good predictive value for the etiology of ICAS-LVO.The optimal cut-off value of HIR was 0.26,with an AUC value of 0.74,a specificity of 0.88,and a sensitivity of 0.54.The optimal cutoff for the mismatch ratio was 3.84,with an AUC value of 0.84,a specificity of 0.75,and a sensitivity of 0.90.Generalized linear model revealed that HIR and cerebral blood volume index had no signifi-cant difference in prognostic performance(P=0.175).Conclusion HIR and mismatch ratio are helpful to identify the pathogenesis earlier and formulate surgical strategies more accurately,thereby reducing iatrogenic injury to a greater extent,increasing the effective reperfusion rate,re-ducing the disability and mortality,and improving the prognosis of clinical outcomes.