BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

AIM:To investigated the mechanism of action of Yiqi tongfu xiere prescription(YTX)in treating mice with lipopolysaccharide(LPS)-in-duced acute lung injury(ALI).METHODS:According to the random number table,24 C57BL/6 mice were divided into 4 groups:control group(Control),model group(LPS),low dose group(YTX-L)and high dose group(YTX-H).Except for the control group,the mice models of acute lung injury were established by intratracheal instillation of LPS solu-tion(5 mg/kg).The low and high dose treatment groups were given intragastric administration con-tinuously for 14 days.After 24 hours,the lung tis-sue,bronchoalveolar lavage fluid(BALF)and serum of the four groups were taken for follow-up detec-tion.The degree of pulmonary edema was evaluat-ed by wet weight coefficient(wet to dry ratio,W/D)of lung tissue.The degree of alveolar inflamma-tion and pulmonary fibrosis were evaluated by HE and Masson staining,and the contents of BALF and serum inflammatory cytokines IL-1β and IL-6 were detected by ELISA.The protein expressions of α-SMA,FN,Col-Ⅰ and Col-Ⅲ were measured by West-ern blot.Determination of α-SMA,FN,Col-Ⅰ,MAPK,NF-κB mRNA expression by RT-PCR method.RE-SULTS:Compared with LPS group,the contents of BALF,IL-1β and IL-6 in serum,Wmax D ratio,lung pathology,serum α-SMA,FN,Col-Ⅰ,Col-Ⅲ protein expression and α-SMA,FN,Col-Ⅰ,MAPK,NF-κB mRNA expression in treatment group were signifi-cantly lower than those in control group.CONCLU-SION:YTX can significantly reduce the levels of pul-monary fibrosis markers such as α-SMA,FN,Col-Ⅰand Col-Ⅲ by inhibiting the activation of MAPK/NF-κB signal pathway,and improve alveolar inflamma-tion and pulmonary fibrosis in mice with lung inju-ry,suggesting that YTX can treat acute lung injury and provide a theoretical basis for the clinical use of YTX.

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

AIM:To investigated the mechanism of action of Yiqi tongfu xiere prescription(YTX)in treating mice with lipopolysaccharide(LPS)-in-duced acute lung injury(ALI).METHODS:According to the random number table,24 C57BL/6 mice were divided into 4 groups:control group(Control),model group(LPS),low dose group(YTX-L)and high dose group(YTX-H).Except for the control group,the mice models of acute lung injury were established by intratracheal instillation of LPS solu-tion(5 mg/kg).The low and high dose treatment groups were given intragastric administration con-tinuously for 14 days.After 24 hours,the lung tis-sue,bronchoalveolar lavage fluid(BALF)and serum of the four groups were taken for follow-up detec-tion.The degree of pulmonary edema was evaluat-ed by wet weight coefficient(wet to dry ratio,W/D)of lung tissue.The degree of alveolar inflamma-tion and pulmonary fibrosis were evaluated by HE and Masson staining,and the contents of BALF and serum inflammatory cytokines IL-1β and IL-6 were detected by ELISA.The protein expressions of α-SMA,FN,Col-Ⅰ and Col-Ⅲ were measured by West-ern blot.Determination of α-SMA,FN,Col-Ⅰ,MAPK,NF-κB mRNA expression by RT-PCR method.RE-SULTS:Compared with LPS group,the contents of BALF,IL-1β and IL-6 in serum,Wmax D ratio,lung pathology,serum α-SMA,FN,Col-Ⅰ,Col-Ⅲ protein expression and α-SMA,FN,Col-Ⅰ,MAPK,NF-κB mRNA expression in treatment group were signifi-cantly lower than those in control group.CONCLU-SION:YTX can significantly reduce the levels of pul-monary fibrosis markers such as α-SMA,FN,Col-Ⅰand Col-Ⅲ by inhibiting the activation of MAPK/NF-κB signal pathway,and improve alveolar inflamma-tion and pulmonary fibrosis in mice with lung inju-ry,suggesting that YTX can treat acute lung injury and provide a theoretical basis for the clinical use of YTX.

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

Objective:To assess the practical value of visual scores of magnetic resonance imaging(MRI)features in the diagnosis and classification of dementia with Lewy bodies(DLB).Methods:In this study, 102 DLB patients were prospectively recruited, with 102 cognitively normal elderly people as the normal control group(NC).All included subjects underwent MRI examinations and neuropsychological assessments.Based on the clinical dementia rating(CDR)scale, DLB patients were divided into a mild(CDR=1.0), a moderate(CDR=2.0)and a severe(CDR=3.0)group.The results of MRI were scored visually and the rating scales included medial temporal lobe atrophy(MTA), global cortical atrophy-frontal subscale(GCA-F), posterior cortical atrophy(PCA), white matter lesions(the Fazekas scale), cerebral microbleeds(CMBs), and the Evans Index(EI).Statistical differences were compared between the DLB and NC groups and between DLB patients with different degrees of cognitive impairment.Results:In terms of neuropsychology, the Mini-Mental State Examination(MMSE) score of the DLB group[16.0(11.0, 21.0)]was statistically significantly lower than that of the NC group[29.0(28.0, 30.0)]( Z=-12.31, P<0.001), the Montreal Cognitive Assessment(MoCA)score of the DLB group[9.5(6.0, 15.0)]was statistically significantly lower than that of the NC group[28.0(27.0, 29.0)]( Z=-12.40, P<0.001), and the Activities of Daily Living(ADL)score of the DLB group[32.0(23.8, 40.0)]was statistically significantly higher than that of the NC group[20.0(20.0, 20.0)]( Z=-11.98, P<0.001).The scores of all MRI visual assessment scales in DLB patients were statistically significantly higher than those in the NC group( P<0.001).There were significant differences in MTA scores between DLB patients with different degrees of cognitive impairment( P0<0.001).The MTA score of the mild group[1.0(1.0, 1.0)]was statistically significantly lower than that of the moderate group[2.0(1.0, 2.0)]( P1<0.001, P2<0.001); The MTA score of the moderate group[2.0(1.0, 2.0)]was statistically significantly lower than that of the severe group[2.0(2.0, 3.0)]( P1=0.003, P2=0.010). Conclusions:This study has for the first time after comprehensively evaluated the value of various visual scores in DLB diagnosis, MTA can be used to help diagnose DLB and distinguish the severity of DLB, providing a new supplemental tool for clinical diagnosis.

Dementia with Lewy bodies(DLB)is the second most common neurodegenerative dementia after Alzheimer's Disease(AD). This article will mainly elaborate the relationship between DLB and blood-brain barrier(BBB)from the following five aspects: (1)The structure and function of BBB; (2)In vivo assessment methods for the blood-brain barrier damage; (3)Evidence for the damage of blood-brain barrier in DLB; (4)The relationship between α-synuclein and the blood-brain barrier; (5)The relationship between APOE and the blood-brain barrier.Future research should focus on the pathogenesis of BBB damage in DLB patients, by which new drug targets for disease diagnosis and treatment may be found.

Objective:To explore the effect of the application of nursing decision support information system in the continuing nursing of stroke patients in convalescent period, and to provide guidance for the information-based whole process nursing of stroke patients in convalescent period.Methods:A total of 107 stroke patients in convalescent period admitted to 4 Grade Ⅲ Level A hospitals of Beijing city from March to November 2019 were selected. The patients were divided into control group (53 cases) and test group (54 cases) by coin tossing method. The control group followed uniformly formulated discharge health education manual for post-discharge management and follow-up, while the test group received health guidance and follow-up through the nursing decision support information system. Barthel Index and MOS SF-36 were used to evaluate the activities of daily living and quality of life of the two groups of patients before intervention and 3 and 6 months after the intervention, and the results were compared.Results:There was no significant difference in Barthel Index before the intervention between the two groups( P>0.05). After 3 months of intervention, the Barthel Index ≤ 49, 50-70 and ≥ 71 in the test group were 7, 17 and 27 cases respectively, and 16, 21 and 13 cases in the control group respectively, and the difference between the two groups was statistically significant ( Z=-2.95, P<0.01). After 6 months of intervention, the Barthel Index ≤ 49, 50-70 and ≥ 71 in the test group were 7, 12 and 32 cases respectively, and 10, 15 and 25 cases in the control group respectively,and the difference between the two groups was statistically significant ( Z=-2.21, P<0.05). There was no significant difference in MOS SF-36 before the intervention between the two groups( P>0.05). After 3 and 6 months of intervention, the total score of MOS SF-36 in the test group was (50.51 ± 14.57), (57.06 ± 14.85) respectively, and that in the control group was (42.02 ± 15.48), (45.58 ± 14.97) respectively, and the differences between the two groups were statistically significant ( t=2.84, 3.23, both P<0.05). Conclusions:The application of nursing decision support information system can effectively improve the daily life ability of patients, enhance the quality of life of patients.

Objective: To investigate the prevalence of autonomic dysfunction and its influencing factors in the elderly in Jizhou community of Tianjin. Methods: By using a cross-sectional study, a questionnaire survey was conducted in the elderly in order to investigate the prevalence of autonomic dysfunction and its influencing factors. Results: A total of 1 292 elderly patients were enrolled.Of them, 196 cases had autonomic dysfunction(15.2%, 196/1 292). The main symptoms of autonomic dysfunction were frequent urination, urination urgency, urination incontinence(19.7%, 255/1 292)and constipation(15.9%, 205/1 292). Multivariate Logistic regression analysis showed that women(OR=1.808, 95%CI: 1.253~2.607), 75-85 years of age(OR=1.573, 95%CI: 1.109~2.232), general anesthesia history(OR=1.552, 95%CI: 1.044~2.307), sleep disorders(OR=2.906, 95%CI: 1.506~2.916), diabetes(OR=1.791, 95%CI: 1.197~2.678)and headache(OR=2.589, 95%CI: 1.482~4.520)were risk factors for autonomic dysfunction. Conclusions The prevalence of autonomic dysfunction is high in the elderly in Jizhou community of Tianjin city.It is necessary to pay great attention to potential risk factors of autonomic dysfunction in the elderly.And the autonomic dysfunction symptoms should be diagnosed and treated as early as possible.

Neurofibrillary tangle-predominant dementia(NFTPD)is one type of late-onset dementia, with memory disorders as the main clinical manifestation.The pathological feature is the presence of a large number of neurofibrillary tangle(NFT)in the hippocampus with no or little amyloid deposition in the brain.In recent years, primary age-related tauopathy(PART)has been proposed as a new pathological term, which means that NFT appears in the medial temporal lobe with aging, but no amyloid deposits, and NFTPD is one type of dementia associated with the progression of PART.