Purpose To explore the pathological features of angioimmunoblastic T-cell lymphoma(AITL)with bone marrow involvement and to improve awareness of bone marrow infiltration in AITL.Methods The tissue morphology of 32 cases of AITL with bone marrow involvement was retrospectively analyzed.Im-munohistochemistry using the EnVision method and ten-color flow cytometry were conducted to detect AITL-related immune markers.T cell clonality was analyzed through T cell receptor(TCR)gene rearrangement.Results The predominant pat-terns of tumor cell infiltration were nodular(20/32,62.5％)and interstitial or small clusters(10/32,31.3％).The nodules showed a mixture of cellular components.In some cases,the fo-ci contained a mixture of cells with characteristic"granuloma-toid"changes.The tumor cells were mainly small to medium-sized lymphocytes with inconspicuous atypia.Some cases showed plasma cell proliferation.19 cases were subject to immunohisto-chemical staining,which revealed a low count of CD4-positive T cells,with an average of 8.4％.The positive rates of T follic-ular helper cells(TFH)markers were as follows:CD10(7/14,50.0％),BCL6(6/19,31.6％),PD-1(13/19,68.4％),and CXCL13(13/19,68.4％).In most cases,tumor cells showed co-expression of PD-1 and CXCL13,but the number of positive cells was less than 1％.Flow cytometry analysis was performed in 24 cases,among which 22 cases all consistently expressed cytoplasmic CD3(cCD3),CD5,CD4,and CD2,with varying degrees of CD10 expression.In some cases,there was a lack of expression of surface CD3(sCD3)(12/22,54.5％),while there was a lack of expression of CD7(8/22,36.4％).and no abnormal T cells were found in 2 cases.TCR gene rearrangement analysis was performed in 7 cases,with 3 cases showing TCR clonality.Conclusion AITL with bone marrow involvement exhibits a lower proportion of tumor cells and less atypia,making it prone to misdiagnosis.The presence of lymphocytic foci with mixed cellular components in the bone marrow can indicate bone marrow involvement in AITL.Flow cy-tometry detection of abnormal T cells(double positive for CD4 and CD10)strongly suggests bone marrow infiltration in AITL.A comprehensive diagnosis of bone marrow involvement in AITL re-quires consideration of bone marrow biopsy,flow cytometry,and TCR gene rearrangement analysis.

The latest research findings on bidirectional regulation of neuro-immunity through traditional neural circuits shed new light on the theoretical basis of the role of vidian neurectomy (VN). This article aims to provide a comprehensive understanding of VN, including the history of VN, the principle of neuroimmuno-interaction, the applied anatomy of VN as well as the methods of transnasal endoscopic surgery. Additionally, we introduce the concept of the nose-brain axis, which was proposed based on the advancement in the area of neuro-immune interactions.

ObjectiveTo explore the mechanism of Dihuang Yinzi in improving astrocyte injury and glycolysis in Alzheimer's disease （AD） mice via regulating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， thereby improving the cognitive function of AD mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. The mice in the control + Dihuang Yinzi group and the model + Dihuang Yinzi group were administered with Dihuang Yinzi by gavage， and those in the control group and the model group received an equal volume of sterilized normal saline， once a day for 150 days. Morris water maze test was performed to test the ability of navigation and space exploration of mice. The protein expression of p-PI3K， PI3K， p-Akt， Akt， phosphofructokinase-1 （PFK-1）， and aldehyde dehydrogenase 3 family member B2 （ALDH3B2） in mouse brain tissues was measured by Western blot. An immunofluorescence assay was performed to detect astrocyte morphology and the expression level of ALDH3B2. ResultAs compared with the control group， the model group showed prolonged escape latency during the 2^nd to 5^th days of the location-based navigation （P<0.05， P<0.01）， reduced number of times crossing the target area of the platform， shortened residence time in the target quadrant （P<0.05， P<0.01）， prolonged residence time in the opposite quadrant （P<0.05）， increased surface area of the cell body and total length of cell protrusions of astrocytes （P<0.05， P<0.01）， and down-regulated protein expression of p-PI3K， p-Akt， ALDH3B2， and PFK-1 （P<0.01）， while the above experimental indexes were not significantly different in the control + Dihuang Yinzi group. Compared with the model group， the model + Dihuang Yinzi group showed shortened escape latency of APP/PS1 mice during the 2^nd to 5^th days of the location-based navigation （P<0.05， P<0.01）， increased number of times crossing the platform， prolonged target quadrant residence time （P<0.05， P<0.01）， shortened residence time in the opposite quadrant （P<0.05）， reduced surface area of the cell body and total length of cell protrusions of astrocytes （P<0.05）， and up-regulated protein expression of p-PI3K， p-Akt， ALDH3B2， and PFK-1 （P<0.01）. ConclusionDihuang Yinzi can improve the learning and memory ability of AD mice by activating the PI3K/Akt signaling pathway and up-regulating the protein expression of PFK-1 and ALDH3B2 to protect against astrocyte injury in brain tissues and improve glycolysis.

ObjectiveTo explore the mechanism of Dihuang Yinzi （DHYZ）in improving astrocyte injury in the brain and regulating energy metabolism and autophagy disorder in Alzheimer's disease （AD） model mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + DHYZ group （2.5 g·kg^-1）， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + DHYZ group （2.5 g·kg^-1）， with 20 mice in each group. The mice in the control group and the model group were administered with an equal volume of sterilized normal saline by gavage， once a day for 150 days. Novel object recognition test and step-down test were performed to evaluate the learning and memory ability of mice. The expression of glial fibrillary acidic protein （GFAP） in astrocytes was detected by immunofluorescence and Western blot. High-performance liquid chromatography （HPLC） was used to detect adenosine triphosphate （ATP）， adenosine diphosphate （ADP）， and adenosine monophosphate （AMP） in brain tissues of mice， and the data obtained were used to calculate energy charge （EC） levels. The phosphorylation levels of liver kinase B1 （LKB1）， adenosine 5′-monophosphate （AMP）-activated protein kinase （AMPK）， UNC-51-like kinase 1 （ULK1）， and mammalian target of rapamycin （mTOR） and the expression levels of autophagy-related proteins Beclin-1， microtuble-associated protein 1 light chain 3 （LC3）-Ⅱ/LC3-Ⅰ， and p62 in mouse brain were measured by Western blot. ResultCompared with the control group， the model group showed decreased novel object recognition index， shortened retention latency， increased error times in the step-down test， up-regulated protein expression of GFAP， decreased content of ATP， ADP， and EC in brain tissues， elevated AMP ， increased levels of p-AMPK， p-LKB1， and p-mTOR， and protein expression of p62 ， and down-regulated p-ULK1 level and protein expression of Beclin-1 and LC3-Ⅱ/LC3-Ⅰ（P<0.01）， while the above experimental indexes were not significantly different in the control + DHYZ group. Compared with the model group， the model + DHYZ group showed increased novel object recognition index（P<0.05）， prolonged retention latency（P<0.01）， decreased error times（P<0.01） in the step-down test， reduced protein expression of GFAP（P<0.05）， increased content of ATP， ADP， and EC in brain tissues （P<0.05， P<0.01）， decreased AMP content（P<0.05）， reduced p-AMPK， p-LKB1， and p-mTOR levels and protein expression of p62， and up-regulated p-ULK1 level and protein expression of Beclin-1 and LC3-Ⅱ/LC3-Ⅰ（P<0.01）. ConclusionBy protecting astrocytes， DHYZ can improve energy metabolism and autophagy disorder in AD mice to improve the learning and memory ability of model mice.

ObjectiveTo investigate the mechanism of Dihuang Yinzi in improving astrocyte injury and protecting synaptic structure and function in the brain of Alzheimer's disease （AD） mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + Dihuang Yinzi （0.25 g·kg^-1） group， with 20 mice in each group. The mice in the control + Dihuang Yinzi group and the model + Dihuang Yinzi group were administered with Dihuang Yinzi by gavage， and those in the control group and the model group received an equal volume of sterilized normal saline， once a day for 150 days. The learning and memory ability of mice was tested by the light-dark box test and Y-maze spontaneous alternation test. The content of glutamate （Glu） and glutamine （Gln） was measured by liquid chromatography-tandem mass spectrometry （LC-MS）. Long-term potentiation （LTP） assay was used to detect synaptic plasticity in brain tissues. The protein expression levels of excitatory amino acid transporter 2 （EAAT2）， postsynaptic density protein95 （PSD95）， and synaptophysin （SYN） in brain tissues were measured by Western blot. Immunofluorescence was used to assess the localization and expression of EAAT2. Colorimetry was performed to detect Na⁺-K⁺ ATPase activity in mouse brain tissues. ResultAs compared with the control group， the model group showed shortened residence latency （P<0.01）， increased number of errors （P<0.01） in the light-dark box test， reduced spontaneous alternation behaviors （P<0.01）， no significant difference in the total number of arm entries in the Y-maze spontaneous alternation test， down-regulated expression of EAAT2， PSD95， and SYN （P<0.01）， blunted activity of Na⁺-K⁺ ATPase （P<0.01）， up-regulated Glu level （P<0.01）， down-regulated Gln level （P<0.01）， and reduced relative population spike （PS） amplitude and the slope of excitatory postsynaptic potential （EPSP） （P<0.05， P<0.01）， while the above experimental indexes were not significantly different in the control + Dihuang Yinzi group. Compared with the model group， the model + Dihuang Yinzi group displayed prolonged residence latency （P<0.05）， decreased number of errors （P<0.01） in the light-dark box test， increased spontaneous alternation behaviors （P<0.01）， no significant difference in the total number of arm entries in the Y-maze spontaneous alternation test， up-regulated expression of EAAT2， PSD95， and SYN （P<0.01）， potentiated activity of Na⁺-K⁺ ATPase （P<0.01）， reduced Glu level （P<0.01）， up-regulated Gln level （P<0.01）， and increased PS amplitude and EPSP slope （P<0.01）. ConclusionDihuang Yinzi can improve cognitive dysfunction in AD mice by protecting astrocytes， increasing Glu uptake to reduce its abnormal accumulation， and protecting synaptic structure and function.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective:To explore implementation of post training in Central Sterile Supply Department (CSSD) based on Analysis, Design, Development, Implementation and Evaluation model (ADDIE model) , so as to explore its training effects.Methods:From January to August 2021, the development of post training courses for CSSD were completed according to ADDIE model, and 54 CSSD staff in the Second Hospital of Jilin University were selected by the convenient sampling method for post training. After the training, the Korotkoff evaluation method was used to evaluate the training effect from the aspects of CSSD staff satisfaction, theoretical assessment results and implementation rate of key technologies.Results:The satisfaction of CSSD staff with post training based on the ADDIE model was (88.44±4.01) , which was higher than the (79.72±4.90) of traditional training, and the difference was statistically significant ( P<0.01) . After the post training based on the ADDIE model, the theoretical assessment score of CSSD staff was (90.07±6.09) , and the score before training was (81.30±7.28) , and the difference was statistically significant ( P<0.05) . In addition, the implementation rate of the key technologies of the posts was higher than before the training. Except for the sterilization post, there were statistically significant differences in the cleaning post, packaging post, distribution post and receiving post ( P<0.05) , and the frequency of adverse events was 0. Conclusions:Post training based on the ADDIE model can effectively improve the ability of CSSD staff and promote positive changes in their work behavior. Both CSSD staff and hospitals have a high degree of recognition for this training.

Objective:To explore the feasibility of CT angiography (CTA) in investigating vascular dilatation of anterior choroidal artery (AChA) and posterior communicating artery (PComA) in patients with Moyamoya syndrome (MMS).Methods:From July 2017 to July 2018, the clinical and imaging data of MMS patients with brain CTA and DSA performed were analyzed retrospectively. According to DSA results, 71 MMS patients were divided into unilateral MMS group (20 cases, 20 hemispheres) and bilateral MMS group (51 cases, 102 hemispheres). There were 20 cases in unilateral MMS group, 10 males and 10 females, with an average age of (45±9) years; 51 cases in bilateral MMS group, 24 males and 27 females, with an average age of (44±12) years. The hemispheres were divided into dilated group and non-dilated group according to the dilatation of AChA or PComA. Kappa analysis was used to evaluate the consistency of two inspection methods to judge the expansion of AChA. The lumen diameters of PComA, P1 and P2 segments of posterior cerebral artery were measured on CTA images, and the ratio of PComA/P1 and PComA/P2 were calculated. The repeatability of CTA measures was evaluated by intra-group correlation coefficient. Independent sample t-test was used to compare CTA measurement results between PComA dilated group and non-dilated group, and ROC curve was drawn to calculate the best threshold for diagnosis of PComA expansion. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of CTA measures were calculated. Results:The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of CTA diagnosis of AChA expansion inunilateral MMS were all 100.00%. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of CTA diagnosis of AChA expansionin bilateral MMS were 90.00%, 93.90%, 93.14%, 78.26% and 97.47%. Compared with DSA, there was no significant difference in the diagnostic performance of AChA expansion between single and bilateral MMS diagnosed by CTA ( P>0.05). The two methods had strong consistency (Kappa value was 1.00 and 0.79 respectively, P<0.01). A total of 46 patients (69 cerebral hemispheres) were included in the evaluation of PComA. PComA/P1 (1.09±0.41) and PComA/P2 (0.86±0.13) in the dilated group were significantly higher than those in the non-dilated group (0.71±0.21 for PComA/P1 and 0.75±0.23 for PComA/P2). The differences were statistically significant ( t=-4.59, -2.50, P<0.05). The best threshold in diagnosing PComA expansion was 0.87 (PComA/P1) and 0.76 (PComA/P2), and the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 84.62%, 83.33%, 84.06%, 86.84%, 80.65% and 79.49%, 60.00%, 71.01%, 72.09% and 69.23%, respectively. Compared with DSA, the Kappa value of CTA measures in diagnosis of PComA expansion was 0.68 (PComA/P1) and 0.40 (PComA/P2), respectively, and the difference was statistically significant ( P<0.05). Conclusions:CTA has a strong consistency with DSA in evaluating the AChA expansion in MMS. When the PComA/P1 ratio on CTA is greater than 0.87, it can be used as the diagnosis criterion for PComA expansion.

Objective: To evaluate the effect of dexmedetomidine on postoperative cognitive function in the patients with mild hyperbilirubinemia caused by choledocholithiasis. Methods: One hundred and twenty patients of both sexes with mild hyperbilirubinemia (serum total bilirubin levels 21-170 μmol/L) caused by choledocholithiasis, aged 51-63 yr, with body mass index of 20-28 kg/m², of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with preoperative Mini-Mental State Examination (MMSE) scores≥20, scheduled for elective cholecystectomy and choledocholithotomy, were divided into 3 groups (n=40 each) using a random number table method: control group (C group) and dexmedetomindine 0.4 μg·kg^-1·h^-1 group (D1 group) and dexmedetomindine 0.6 μg·kg^-1·h^-1 group (D2 group). After induction of anesthesia, dexmedetomidine was intravenously infused for 10 min in a loading dose of 0.5 μg/kg, followed by an infusion of 0.4 and 0.6 μg·kg^-1·h^-1 until the end of operation in D1 and D2 groups, respectively.The equal volume of normal saline was given instead in group C. with preoperative scores≥20, MMSE and Montreal Cognitive Assessment (MoCA) were used to assess the cognitive function at 1 day before operation (T₀) and 1, 3, 5 and 7 days after operation (T_1-4). The occurrence of cognitive dysfunction within 7 days after operation was recorded.Venous blood samples were collected at the time points mentioned above, and the plasma concentrations of β-amyloid (Aβ) 42 were determined by enzyme-linked immunosorbent assay. Results: Compared with group C, MoCA scores were significantly increased at T₁ in group D₁, and MMSE scores at T₁ and MoCA scores at T₁ and T₂ were significantly increased, and the plasma concentrations of Aβ42 were decreased at T_2-4 in group D2, and the incidence of cognitive dysfunction was significantly decreased in D1 and D2 groups (P<0.05). Compared with group D1, MoCA scores were significantly increased at T₁, and the plasma concentrations of Aβ42 were decreased at T_2-4 in group D2 (P<0.05). Conclusion Dexmedetomidine can improve postoperative cognitive function, and intravenous infusion at a rate of 0.6 μg·kg^-1 · h^-1 provides better efficacy for the patients with mild hyperbilirubinemia caused by choledocholithiasis.