Microglia are specialized immune cells in the brain, primarily responsible for clearing debris and responding to inflammation. One of the pathological features of Alzheimer's disease (AD) is the extensive activation of immune system in the brain, and the dynamic changes and dysfunction of microglia could become key factors for AD progression. This article reviews the research progress of regulated effect of microglial on AD pathology, and summarizes its potential value in AD treatment, in order to provide theoretical basis for exploring new therapeutic strategies and intervention targets for AD.

Microglia are specialized immune cells in the brain, primarily responsible for clearing debris and responding to inflammation. One of the pathological features of Alzheimer's disease (AD) is the extensive activation of immune system in the brain, and the dynamic changes and dysfunction of microglia could become key factors for AD progression. This article reviews the research progress of regulated effect of microglial on AD pathology, and summarizes its potential value in AD treatment, in order to provide theoretical basis for exploring new therapeutic strategies and intervention targets for AD.

AIM:To investigate the activation of Cl-channels by sodium taurocholate(NaTC)in mouse pan-creatic acinar cells.METHODS:The single isolated pancreatic acinar cells from FVB/N mice were prepared using colla-genase digestion method.Whole-cell patch clamp technique was performed to record the currents.Intracellular adenosine triphosphate(ATP)dependence of the channels was examined via eliminating ATP from the pipette solution.Anion per-meability of the channels was investigated with ion-exchange method.The pharmacological characteristics of the channels was confirmed by two Cl-channel blockers.The volume sensitivity of the channels was detected using 47%hypertonic bathing solution.Extracellular Ca2+dependence of activating the channels was examined through eliminating Ca2+from the bathing solution.Intracellular reactive oxygen species(ROS)level was detected by an oxidation-sensitive fluorescent probe,2',7'-dichlorofluorescin diacetate.The experiment was repeated 6 times in each group.RESULTS:Extracellular application of 5 mmol/L sodium taurocholate induced a Cl-current,exhibiting the properties of outward-rectification,a se-lectivity sequence of I->Br-≥Cl->gluconate-and intracellularATP dependence(P<0.01).The currents were inhibited by chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate(DIDS)and tamoxifen and by 47%hypertonicity stimulation(P<0.01).When ROS production was scavenged by N-acetyl-L-cysteine,the sodi-um taurocholate-induced Cl-currents were unaffected.The effect of sodium taurocholate on ROS production did not alter with the treatment with DIDS.Sodium taurocholate failed to induce Cl-currents when Ca2+was absent in extracellular bath-ing solution(P>0.05).CONCLUSION:Sodium taurocholate activates Cl-channels in mouse pancreatic acinar cells,which is dependent on extracellular Ca2+but not ROS pathway.

Objective:To investigate the difference in the proportions of T-lymphocyte subsets and the immunological monitoring profiles between patients with B-lymphoproliferative disorder(B-LPD) and healthy individuals.Methods:This clinical observational study involved 194 B-LPD patients [122 males, 72 females, average age (64±20)] treated in Qilu Hospital of Shandong University from May 14th, 2022 to January 19th, 2024. The patient cohort included 76 cases of chronic lymphocytic leukemia (CLL), 23 cases of diffuse large B-cell lymphoma (DLBCL), 17 cases of follicular lymphoma (FL), 12 cases of hair-cell leukemia (HCL), 10 cases of lymphoplasmacytic lymphoma/Waldenstr?m macroglobulinemia (LPL/WM), 26 cases of mantle cell lymphoma (MCL), 20 cases of marginal zone lymphoma (MZL), and 10 cases of unclassified CD5 -B lymphocytic proliferative disease unclassified (B-LPD-U). At the same time, 45 health control (HC) samples [22 males, 23 females, aged 62(±17)] from the medical examination center of our hospital in November 18th, 2023 were collected. The T cell subsets were meticulously analyzed using flow cytometry, including CD4 +naive T cell [CD4 +TN (CD3 +CD4 +CD45RA +CD62L +) ], CD4 +central memory T cell [CD4 +TCM (CD3 +CD4 +CD45RA -CD62L +) ], CD4 +terminally differentiated effector memory cells expressing CD45RA [CD4 +TEMRA (CD3 +CD4 +CD45RA +CD62L -) ], CD4 +effector memory T cell [CD4 +TEM (CD3 +CD4 +CD45RA -CD62L -) ], CD8 +TN (CD3 +CD8 +CD45RA +CD62L +), CD8 +TCM (CD3 +CD8 +CD45RA -CD62L +), CD8 +TEMRA (CD3 +CD8 +CD45RA +CD62L -), CD8 +TEM (CD3 +CD8 +CD45RA -CD62L -), naive regulatory T cell [nTreg (CD3 +CD4 +CD127 dim+CD25 +CD45RA +) ], memory Treg [mTreg (CD3 +CD4 +CD127 dim+CD25 +CD45RA -) ] and activated Treg [aTreg (CD3 +CD4 +CD127 dim+CD25 +HLA-DR +) ]. The difference of T cell subsets data were compared by Mann-Whitney test. Result:The proportionof CD3 +T cells within lymphocyte in B-LPD groups (CCL group 13.15%, DLBCL group 41.75%, FL group 30.52%, HCL group 34.24%, LPL/WM group 40.58%, MCL group 20.67%, MZL group 26.36%, CD5 -B-LPD-U group 17.49%) was significantly lower than HC group (64.85%). The percentage of CD4 +T cells in B-LPD groups (CCL group 46.63%, DLBCL group 40.76%, FL group 42.77%, HCL group 43.81%, LPL/WM group 43.02%, MCL group 45.58%, MZL group 43.95%, CD5 -B-LPD-U group 46.91%) was also significantly lower than HC group (54.61%). Conclusions:B-LPD diseases impair T cell immune function. The increased presence of CD4 +TEM, the reduced level of CD8 +TEMRA and the elevated aTreg suggest that B-LPD may suppress CD8 +T cell-mediated cytotoxicity and enhance the immunosuppressive activity of Treg.

Objective:To investigate the difference in the proportions of T-lymphocyte subsets and the immunological monitoring profiles between patients with B-lymphoproliferative disorder(B-LPD) and healthy individuals.Methods:This clinical observational study involved 194 B-LPD patients [122 males, 72 females, average age (64±20)] treated in Qilu Hospital of Shandong University from May 14th, 2022 to January 19th, 2024. The patient cohort included 76 cases of chronic lymphocytic leukemia (CLL), 23 cases of diffuse large B-cell lymphoma (DLBCL), 17 cases of follicular lymphoma (FL), 12 cases of hair-cell leukemia (HCL), 10 cases of lymphoplasmacytic lymphoma/Waldenstr?m macroglobulinemia (LPL/WM), 26 cases of mantle cell lymphoma (MCL), 20 cases of marginal zone lymphoma (MZL), and 10 cases of unclassified CD5 -B lymphocytic proliferative disease unclassified (B-LPD-U). At the same time, 45 health control (HC) samples [22 males, 23 females, aged 62(±17)] from the medical examination center of our hospital in November 18th, 2023 were collected. The T cell subsets were meticulously analyzed using flow cytometry, including CD4 +naive T cell [CD4 +TN (CD3 +CD4 +CD45RA +CD62L +) ], CD4 +central memory T cell [CD4 +TCM (CD3 +CD4 +CD45RA -CD62L +) ], CD4 +terminally differentiated effector memory cells expressing CD45RA [CD4 +TEMRA (CD3 +CD4 +CD45RA +CD62L -) ], CD4 +effector memory T cell [CD4 +TEM (CD3 +CD4 +CD45RA -CD62L -) ], CD8 +TN (CD3 +CD8 +CD45RA +CD62L +), CD8 +TCM (CD3 +CD8 +CD45RA -CD62L +), CD8 +TEMRA (CD3 +CD8 +CD45RA +CD62L -), CD8 +TEM (CD3 +CD8 +CD45RA -CD62L -), naive regulatory T cell [nTreg (CD3 +CD4 +CD127 dim+CD25 +CD45RA +) ], memory Treg [mTreg (CD3 +CD4 +CD127 dim+CD25 +CD45RA -) ] and activated Treg [aTreg (CD3 +CD4 +CD127 dim+CD25 +HLA-DR +) ]. The difference of T cell subsets data were compared by Mann-Whitney test. Result:The proportionof CD3 +T cells within lymphocyte in B-LPD groups (CCL group 13.15%, DLBCL group 41.75%, FL group 30.52%, HCL group 34.24%, LPL/WM group 40.58%, MCL group 20.67%, MZL group 26.36%, CD5 -B-LPD-U group 17.49%) was significantly lower than HC group (64.85%). The percentage of CD4 +T cells in B-LPD groups (CCL group 46.63%, DLBCL group 40.76%, FL group 42.77%, HCL group 43.81%, LPL/WM group 43.02%, MCL group 45.58%, MZL group 43.95%, CD5 -B-LPD-U group 46.91%) was also significantly lower than HC group (54.61%). Conclusions:B-LPD diseases impair T cell immune function. The increased presence of CD4 +TEM, the reduced level of CD8 +TEMRA and the elevated aTreg suggest that B-LPD may suppress CD8 +T cell-mediated cytotoxicity and enhance the immunosuppressive activity of Treg.

Objective:To analyze the distribution of TCM syndrome elements and syndromes in patients with hypertension with insomnia (HWI) in the real world.Methods:A cross-sectional study and retrospectively enrolled. The positive symptoms and TCM syndrome type entries of 359 patients with HWI who were collected from Henan Integrated Medicine Hospital,Henan Provincial People's Hospital,the First Affiliated Hospital of Henan University of Chinese Medicine from December 2020 to August 2022 were retrospectively studied. Based on factor analysis dimension reduction and systematic cluster analysis, the TCM syndrome elements and potential syndrome types of patients were summarized. The Latern 5.0 software was used to establish a latent structure model and comprehensive clustering based on the mountain climbing method (LTM-EAST) algorithm, and analyze and judge the common syndrome types, providing a basis for proposing the clinical common syndrome types of this disease.Results:Factor analysis extracted 14 common factors, and the cumulative contribution rate was 63.254%. Among the 36 symptom variables with frequency ≥ 70, more than half of the patients with hypertension and insomnia were upset, irritable, less sleepy, dreamy, dizzy, palpitations, stuffy chest, dry mouth, easy to wake up, and tired. The tongue color was mainly light red tongue and red tongue. The tongue is mainly thin and greasy. The first three pulse conditions are string pulse, number pulse and slippery pulse. The disease location and syndrome elements of hypertension with insomnia were mainly liver (52.09%), heart (33.43%), spleen (26.46%) and kidney (23.68%); The disease syndrome elements are mainly phlegm dampness (34.54%), yin deficiency (29.25%), heat (fire) (25.35%), and qi stagnation (25.07%). Ten syndrome types are obtained by frequency statistics, nine syndrome types are obtained by factor clustering, and seven syndrome types are inferred by implicit structure clustering. Among the syndrome types inferred by the above three methods, there are seven syndrome types that recur at least twice, which can be identified as the common syndrome type of hypertension with insomnia.Conclusions:The common clinical symptoms of HWI are upset and irritable, less sleep, more dreams, dizziness, palpitations, stuffy chest, dry mouth, easy to wake up, mental fatigue and body tiredness. The disease location and syndrome elements are mainly in liver, heart, spleen and kidney. The disease mainly involves phlegm dampness, yin deficiency, heat and qi stagnation. The common clinical syndrome types are liver depression transforming fire type, yin deficiency and yang hyperactivity type, phlegm dampness intrinsic type, yin deficiency and internal heat type, heart and gallbladder qi deficiency type, heart and spleen deficiency type, and heart kidney disjunction type.

Objective:To investigate the value of central vein sign (CVS) and iron deposition on quantitative susceptibility imaging (QSM) of 3.0 T MRI in differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disease (NMOSD).Methods:This study was a retrospective study. A total of 54 MS patients and 49 NMOSD patients were enrolled from July 2018 to December 2020 in People′s Hospital of Leshan and the First Affiliated Hospital of Chongqing Medical University. All patients underwent conventional MRI and three-dimensional enhanced T 2*-weighted angiography (3D-ESWAN), and ESWAN-filtered phase and QSM were reconstructed from 3D-ESWAN data. First, brain lesions of MS and NMOSD were screened on proton density (PD)-T 2WI, and then the location of lesions, CVS and nodular/annular iron deposition were observed on phase and QSM images. The χ 2 test was used to compare the differences in intracranial lesion location, CVS and iron deposition between MS and NMOSD patients. Receiver operating characteristic curve and area under the curve (AUC) were used to assess the efficiency of CVS and QSM iron deposition to differentiate MS from NMOSD. Results:A total of 968 MS lesions were observed in 54 MS patients, of which CVSs were found in 354 lesions and 227 CVSs were located around the lateral ventricles, 117 in deep white matter (DWM) and 10 in the cortex/subcortex; 372 lesions showed nodular iron deposition, and 193 lesions ring iron deposition on QSM. Totally 247 brain lesions were observed in 41 of 48 patients with NMOSD, of which CVSs were found in 4 lesions and 1 located around the lateral ventricle, 3 located in the DWM; 3 lesions showed nodular iron deposition on QSM. There were significant differences in cortex/subcortex lesions, CVS and iron deposition between MS and NMOSD patients (χ 2 were 29.33, 115.66 and 258.21, respectively, all P<0.001). The AUC of CVS for differentiating MS from NMOSD was 0.941 (95%CI 0.887-0.994), with a sensitivity of 96.3% and a specificity of 91.8%; the AUC of iron deposition for differentiating MS from NMOSD was 0.969 (95%CI 0.930-1.000), with a sensitivity of 100% and a specificity of 93.9%. Conclusion:CVS and iron deposition on 3.0 T MRI are distinct radiologic features of MS lesions from those of NMOSD lesions, and have certain value in the differential diagnosis.

Objective:To investigate the current status of knowledge, attitude and practice of palliative care among nurses in 10 general hospitals in Beijing and explore its influencing factors, so as to provide a reference for further training and management of palliative care.Methods:From March to April 2020, convenience sampling was used to select nurses from 10 general hospitals in Beijing for investigation with three questionnaires on knowledge, attitude and behavior of palliative care in Chinese. A total of 850 questionnaires were returned and 833 valid questionnaires were collected, with a valid rate of 98.00%. Multiple linear regression analysis was used to analyze the influencing factors of knowledge, attitude and behavior of palliative care among nurses.Results:The overall score for palliative care of nursing staff in 10 general hospitals in Beijing was (82.16±8.73) , with a score rate of 68.47%. The knowledge score was (12.36±4.14) with a score rate of 61.80%, and the attitude score was (36.85±3.97) with a score rate of 61.42%, and the behavior score was (32.95±5.84) with a score rate of 82.37%. Multiple linear regression analysis showed that participation in palliative care training, gender, job title, knowledge and attitude, and monthly income were the main influencing factors of nurses' knowledge, attitude and behavior on palliative care ( P<0.05) . Conclusions:The current status of palliative care awareness among nurses in Beijing general hospitals is at an intermediate level and needs to be further improved. Nursing managers should strengthen the training and education of nursing staff, improve relevant knowledge, palliative care attitudes and professional enthusiasm, so as to promote behavioral changes and improve the quality of clinical nursing.

【Objective】 To evaluate the efficacy and safety of early interventions by traditional Chinese medicine oral liquid combined with plasma exchange in the treatment of pregnant women with high titer of ABO/Rh antibodies. 【Methods】 156 pregnant women with serum antibodies presenting high titer (ABO ≥512, Rh ≥ 64) in our hospital from May 2018 to April 2021 were randomly divided into traditional Chinese medicine group(group Ⅰ, n=68), traditional Chinese medicine combined with plasma exchange group(group Ⅱ, n=57) and control group (n=31). The control group were given VC, VEand oxygen uptake. Group Ⅰ were further given oral administration of traditional Chinese medicine liquid on the basis of treatment of the controls. GroupⅡwas further treated with plasma exchange on the basis of group I treatment(for 20 days every month). The biochemistry, serum antibody titer and foetus intrauterine growth were monitored. The the efficacy of treatment, as well as pregnancy and neonatal conditions in the three groups were observed. 【Results】 The decrease time of antibody titer and IgG subtype titer in groupⅠ and Ⅱ, relative to the controls, were significantly better(P<0.05). The effective rate of group Ⅰ(72.59%, 49/68) and group Ⅱ(92.98%, 53 /57) were significantly higher than the controls(18.52%, 5/27, with 4 cases excluded). No HDN occurred in group II, indicating superior treatment outcome to group I and the controls. 【Conclusion】 The oral administration of traditional Chinese medicine liquid combined with plasma exchange, with good therapeutic efficacy and maternal-fetal safety, was effective for the early interventions of ABO/Rh incompatible HDN and worthy of clinical application.

OBJECTIVE: To explore the expression of the RNA-binding protein tristetraprolin in lung adenocarcinoma cells and its molecular mechanism for inhibiting autophagy. METHODS: Quantitative real-time PCR and Western blotting were performed to detect the expression of autophagy-related genes (including Beclin1, LC3-Ⅱ/LC3-Ⅰ and SQSTM1/p62) in cultured lung adenocarcinoma cells at 24, 48 and 72 h after transient transfection with a tristetraprolin-overexpressing plasmid and the empty plasmid. The effects of transfection with the tristetraprolin-overexpressing plasmid and empty plasmids in the presence or absence of tumor necrosis factor- (TNF-) on the expressions of nuclear factor-κB (NF-κB) p65, c-rel, and p50 were examined in lung adenocarcinoma cells using immunofluorescence assay and Western blotting. The cells were also transfected with the IκBα-mut plasmid and the tristetraprolin-overexpressing plasmid, either alone or in combination, and the changes in the expressions of tristetraprolin and autophagy-related genes were detected using RT-qPCR and Western blotting. RESULTS: The expressions of tristetraprolin were significantly reduced at both the mRNA and protein levels in lung adenocarcinoma cells ( < 0.001). Overexpression of tristetraprolin in the cells significantly lowered the expressions of autophagy-related genes Beclin1 and the ratio of LC3-Ⅱ/LC3-Ⅰ at the mRNA and protein levels ( < 0.001), obviously lowered the expressions of NF-κB p65 and c-rel, and almost totally blocked the nuclear translocation of NF-κB p65 and c-rel ( < 0.05); the expression of p50, however, did not undergo significant changes in response to tristetraprolin overexpression ( > 0.05). The inhibitory effect of tristetraprolin overexpression on autophagy was abrogated by transfection of the cells with IκBα-mut plasmid, which blocked the NF-κB signaling pathway. Co-transfection of the cells with IκBα-mut also attenuated the inhibitory effect of tristetraprolin overexpression on Beclin1 and the LC3-Ⅱ/LC3-Ⅰ ratio at both the mRNA and protein levels ( < 0.05). CONCLUSIONS The expression of tristetraprolin is low in lung adenocarcinoma cells. Tristetraprolin overexpression causes inhibition of autophagy in lung adenocarcinoma cells possibly by blocking NF-κB p65 and c-rel nuclear translocation.
Autophagy ; Cell Line ; Humans ; Lung Neoplasms ; NF-kappa B ; Signal Transduction ; Tristetraprolin