Objective To summarize the clinical features,treatment and prognosis of patients with primary central nervous system lymphoma(PCNSL)with clonal bone marrow B cells,and to explore the influence on clinical diagnosis and treatment.Methods PCNSL patients with clonal bone marrow B cells diagnosed by flow cytometry between Jan 2020 and Jul 2023 at Huashan Hospital of Fudan University were enrolled.The auxiliary examination data of these patients were collected,including complete blood count,routine biochemistry,bone marrow aspiration and biopsy,contrast-enhanced brain MRI,and whole-body PET-CT.Kaplan-Meier was used to draw the survival curve,and relevant literature was reviewed.Results A total of 223 newly diagnosed PCNSL patients were included,187 of whom completed bone marrow puncture and biopsy evaluation.We found clonal bone marrow B cells in 16 of 187 cases(8.56%)by flow cytometry.2 patients showed B lymphoma involving the bone marrow.All patients received a high-dose methotrexate based chemotherapy.The median progression free survival(PFS)of 16 patients with clonal bone marrow B cells was 11.1 months,and the median PFS of 171 patients with normal bone marrow was 12.6 months.There was no significant difference in the PFS between the two groups.Conclusion PCNSL with clonal bone marrow B cells had no specific clinical features,but bone marrow flow cytometry showed clonal B cells.High-dose methotrexate treatment regimen is effective.There was no significant difference in PFS for PCNSL patients with clonal B cells and normal findings in bone marrow.Clonal B cells in bone marrow may be caused by monoclonal B-cell lymphocytosis(MBL),lymphoma involves the bone marrow and the presence of common precursor cells.Bone marrow examination should be performed in the initial evaluation of suspected PCNSL.

Objective To summarize the clinical features,treatment and prognosis of patients with primary central nervous system lymphoma(PCNSL)with clonal bone marrow B cells,and to explore the influence on clinical diagnosis and treatment.Methods PCNSL patients with clonal bone marrow B cells diagnosed by flow cytometry between Jan 2020 and Jul 2023 at Huashan Hospital of Fudan University were enrolled.The auxiliary examination data of these patients were collected,including complete blood count,routine biochemistry,bone marrow aspiration and biopsy,contrast-enhanced brain MRI,and whole-body PET-CT.Kaplan-Meier was used to draw the survival curve,and relevant literature was reviewed.Results A total of 223 newly diagnosed PCNSL patients were included,187 of whom completed bone marrow puncture and biopsy evaluation.We found clonal bone marrow B cells in 16 of 187 cases(8.56%)by flow cytometry.2 patients showed B lymphoma involving the bone marrow.All patients received a high-dose methotrexate based chemotherapy.The median progression free survival(PFS)of 16 patients with clonal bone marrow B cells was 11.1 months,and the median PFS of 171 patients with normal bone marrow was 12.6 months.There was no significant difference in the PFS between the two groups.Conclusion PCNSL with clonal bone marrow B cells had no specific clinical features,but bone marrow flow cytometry showed clonal B cells.High-dose methotrexate treatment regimen is effective.There was no significant difference in PFS for PCNSL patients with clonal B cells and normal findings in bone marrow.Clonal B cells in bone marrow may be caused by monoclonal B-cell lymphocytosis(MBL),lymphoma involves the bone marrow and the presence of common precursor cells.Bone marrow examination should be performed in the initial evaluation of suspected PCNSL.

Objective To explore the feasibility and diagnostic value of ultra-fast scanning scheme based on deep learning-based reconstruction(DLR)for cervical MR examination.Methods Thirty-six subjects were prospectively enrolled and underwent both conventional scheme(scan time:6 min 14 s)and ultra-fast scheme(2 min)cervical spine MR scanning to acquire encompassing sagittal T1WI,sagittal adipose suppression T2WI and axial T2WI.The ultra-fast MRI were reconstructed using DLR method.The subjective and objective evaluations on imaging qualities of different MRIs were compared,along with the inter-observer agreement for diagnosing intervertebral disc degeneration and herniation.Results Compared with conventional MRI,artifacts in ultra-fast DLR images significantly reduced(P＜0.05).The subjective evaluation results of MRI had good agreement(all Kappa≥0.60).Compared with conventional MRI,the sagittal T1WI,T2WI and axial T2WI obtained with ultra-fast DLR showed significantly improved signal-to-noise ratio(SNR)of the spinal cord,cerebrospinal fluid(CSF)and vertebral body,as well as the spinal cord/CSF contrast(all P＜0.001).The Kappa value of 2 physicians for diagnosing intervertebral disc degeneration based on ultra-fast DLR and conventional scheme images was 0.94 and 1.00,respectively,of intervertebral disc herniation was 0.96 and 0.98,respectively.Conclusion Compared with conventional scanning scheme,using ultra-fast DLR scheme in cervical MR examination could shorten scanning time while achieve similar image quality and diagnostic accuracy.

Objective To investigate the pass rates of fit tests for various brands of medical protective masks and to explore methods for quickly matching these masks based on their head and face dimensions.Methods A total of 202 medical staff from designated hospitals in Tianjin were selected as subjects.Quantitative fit tests were conducted on 5 brands of masks(A,B,C,D,and E)using an aerosol condensation nucleus counter.Two-dimensional photographic measurement was used to obtain the face length and width of the subjects,categorizing them into face types#1 to#10.The pass rates of masks across different face zones,brands,and face types were compared.Results A total of 202 testers participated in this study.According to the guidelines,face type#1 was the most common[43.6%(88/202)],followed by face type#3[18.2%(37/202)].The majority of subjects were categorized as face types#1,#2,#3,and#4,totaling 176 subjects(87.1%).A total of 914 tests were conducted,with 678 passes,resulting in an overall mask pass rate of 74.18%.The pass rates of masks A,B,and C were significantly higher than those of masks D and E[87.03%(161/185),85.57%,(166/194),82.02%(146/178)vs.62.98%(114/181),51.70%(91/176),all P<0.05].The pass rate of adjustable head-mounted masks was significantly higher than that of non-adjustable masks[79.54%(587/738)vs.51.70%(91/176),P<0.05].The fit factor(FF)for mask B in face types#1 to#5 was significantly higher than that in face types#6 to#10[200(163,200)vs.132(86,200),P<0.05].Conclusions Two-dimensional photographic measurement can quickly obtain facial information of the subjects and match the corresponding masks.Hospitals can match masks with higher test pass rates according to the proportion of face types among medical staff.When selecting masks,preference should be given to adjustable head-mounted masks.

Objective To explore the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP),and reveal its mechanism of resistance to ceftazidime/avibactam(CZA).Methods CZA-re-sistant CRKP strains initially isolated from the Affiliated Hospital of Xuzhou Medical University from January 2021 to September 2023 were collected.The carriage of 5 carbapenemase genes(blaKPC,blaNDM,blaOXA,blaVIM,blaIMp)were detected with gene amplification method and colloidal gold method.The relative copy number and expression level of Klebsiella pneumoniae(KP)carbapenemase-producing KP(KPC-KP)was detected with real-time quantita-tive polymerase chain reaction(RT-qPCR),mutation sites of KPC mutation strains were analyzed with whole-ge-nome sequencing,and epidemic characteristics of CRKP and resistance mechanism to CZA were analyzed.Results A total of 73 CZA-resistant CRKP strains were isolated,with 37(50.68％)being KPC and NDM co-producing strains,33(45.21％)NDM-producing alone(23 strains producing NDM-5 and 10 strains producing NDM-1),and 3 KPC-producing alone.KP-2842 strain was identified as ST11-type KPC-33 variant,KP-2127 and KP-2189 strains produced KPC-2.Compared with KP ATCC BAA-1705,the copy number of blaKPC in these strains up-regulated by 1.04-3.86 fold,and the expression increased by 6.66-12.93 fold,respectively.Colloidal gold and PCR methods demonstrated good consistency and the ability to detect the enzyme co-producing and KPC-33 variant.Conclusion In this hospital,the resistance of CRKP to CZA is primarily mediated by the metalloenzyme NDM,with co-produc-tion of NDM and KPC being a characteristic of CRKP.High copy number and expression level of blaKPC-2 also con-tribute to CZA resistance.This study identified the KPC-33 variant for the first time in ST11-type CRKP in Jiangsu Province.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

Objective To evaluate the effects and the possible mechanisms based on the synaptic plasticity regulated by the orexin signalling pathway of the classic Qing Dynasty prescription AnMeidan(AMD),whose"Raw and cooked jujube kernel"used and without the prescription on learning and memory in a rat model of insomnia.Methods The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine(PCPA)into rats,and AMD was administered by gavage and a decoction of the formula was disassembled.Observing 24 h autonomous activity using the EthoVision XT animal motion trajectory tracking system,Morris water maze was used to evaluate the learning and memory ability;hematoxylin-eosin(HE)and Nissl staining were used to observe the neuronal changes in rat hippocampal CA1 area;Golgi staining and immunohistochemistry(IHC)were used to observe the neuronal dendritic changes in rat hippocampal CA1 area,and the changes in synaptic plasticity proteins,synaptophysin(SYN),microtubule-associated protein 2(MAP-2),glial fibrillary acidic protein43(GFAP-43);Western blotting and Reverse transcription-qPCR(RT-qPCR)were used to detect hippocampal orexin A(OXA)/phosphatidylinositol-specific phosphodiesterase Cβ1(PLCβ-1)/protein kinase Cα(PKCα)/extracellular signalling-regulated kinase(ERK1/2)signalling pathway protein and gene expression.Results Compared with the blank group,the model group showed prolonged upper platform latency,decreased number of crossing stations,decreased distance travelled by periplatform range I activity,the frequency and duration of mania increase,while the frequency and duration of stillness decrease(P<0.01),damaged muscle fibres in the CA1 region of the hippocampus,uneven staining of the nuclei,decreased and disorganized Nyctal microsomes,reduced dendritic spine length and number(P<0.05),and faded staining and decreased expression of SYN,MAP-2,and GFAP-43(P<0.01),hippocampal OXA protein and gene expression increased(P<0.01),and PLCβ-1,PKCα,ERK1/2 protein and gene expression decreased(P<0.01).Compared with the model group,Suvorexant and AMD,AMD desiccated,and cooked jujube seed increased the static frequency、number of times they traversed the station,the distance travelled in the first quadrant and the range of periportal activities,and the time of periportal range I activities(P<0.05,P<0.01);hippocampal muscle fibres were more neatly arranged,the number of Nissin bodies increased,and dendritic spine lengths and numbers were increased(P<0.05),and the SYN,MAP-2,and GFAP-43 expression was elevated(P<0.05,P<0.01),OXA expression was decreased(P<0.01,P<0.05),and PLCβ-1,PKCα,ERK1/2 expression was elevated(P<0.01,P<0.05).Compared with the AMD group,both AMD de-raw and ripe date palm kernel groups could increase the number of times and distances they traversed the stations(P<0.05,P<0.01),decrease the length and number of dendritic spines(P<0.05),decrease the expression of SYN,MAP-2,GFAP-43,and OXA proteins in hippocampal CA1 region(P<0.01),and elevate the PLCβ-1,PKCα,and ERK1/2 expression(P<0.05).Conclusion AMD can regulate the synaptic plasticity of hippocampus in insomniac rats through regulating the OXA/PLCβ-1/PKCα/ERK1/2 signalling pathway to improve the learning memory,the effect of"raw and cooked jujube kernel"used together was better than that of"raw and cooked jujube kernel"used separately.

Objective To evaluate the effects and the possible mechanisms based on the synaptic plasticity regulated by the orexin signalling pathway of the classic Qing Dynasty prescription AnMeidan(AMD),whose"Raw and cooked jujube kernel"used and without the prescription on learning and memory in a rat model of insomnia.Methods The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine(PCPA)into rats,and AMD was administered by gavage and a decoction of the formula was disassembled.Observing 24 h autonomous activity using the EthoVision XT animal motion trajectory tracking system,Morris water maze was used to evaluate the learning and memory ability;hematoxylin-eosin(HE)and Nissl staining were used to observe the neuronal changes in rat hippocampal CA1 area;Golgi staining and immunohistochemistry(IHC)were used to observe the neuronal dendritic changes in rat hippocampal CA1 area,and the changes in synaptic plasticity proteins,synaptophysin(SYN),microtubule-associated protein 2(MAP-2),glial fibrillary acidic protein43(GFAP-43);Western blotting and Reverse transcription-qPCR(RT-qPCR)were used to detect hippocampal orexin A(OXA)/phosphatidylinositol-specific phosphodiesterase Cβ1(PLCβ-1)/protein kinase Cα(PKCα)/extracellular signalling-regulated kinase(ERK1/2)signalling pathway protein and gene expression.Results Compared with the blank group,the model group showed prolonged upper platform latency,decreased number of crossing stations,decreased distance travelled by periplatform range I activity,the frequency and duration of mania increase,while the frequency and duration of stillness decrease(P<0.01),damaged muscle fibres in the CA1 region of the hippocampus,uneven staining of the nuclei,decreased and disorganized Nyctal microsomes,reduced dendritic spine length and number(P<0.05),and faded staining and decreased expression of SYN,MAP-2,and GFAP-43(P<0.01),hippocampal OXA protein and gene expression increased(P<0.01),and PLCβ-1,PKCα,ERK1/2 protein and gene expression decreased(P<0.01).Compared with the model group,Suvorexant and AMD,AMD desiccated,and cooked jujube seed increased the static frequency、number of times they traversed the station,the distance travelled in the first quadrant and the range of periportal activities,and the time of periportal range I activities(P<0.05,P<0.01);hippocampal muscle fibres were more neatly arranged,the number of Nissin bodies increased,and dendritic spine lengths and numbers were increased(P<0.05),and the SYN,MAP-2,and GFAP-43 expression was elevated(P<0.05,P<0.01),OXA expression was decreased(P<0.01,P<0.05),and PLCβ-1,PKCα,ERK1/2 expression was elevated(P<0.01,P<0.05).Compared with the AMD group,both AMD de-raw and ripe date palm kernel groups could increase the number of times and distances they traversed the stations(P<0.05,P<0.01),decrease the length and number of dendritic spines(P<0.05),decrease the expression of SYN,MAP-2,GFAP-43,and OXA proteins in hippocampal CA1 region(P<0.01),and elevate the PLCβ-1,PKCα,and ERK1/2 expression(P<0.05).Conclusion AMD can regulate the synaptic plasticity of hippocampus in insomniac rats through regulating the OXA/PLCβ-1/PKCα/ERK1/2 signalling pathway to improve the learning memory,the effect of"raw and cooked jujube kernel"used together was better than that of"raw and cooked jujube kernel"used separately.

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.
Humans ; Child ; Hepatitis B, Chronic/pathology* ; Retrospective Studies ; Case-Control Studies ; Hepatitis B virus/genetics* ; Liver Cirrhosis/pathology* ; Non-alcoholic Fatty Liver Disease/complications* ; Risk Factors