Objective:To explore the expressions of calcium-activated chloride channel protein 1(ANO1)and E-cadherin in colorectal cancer(CRC)tissue and their relationships with the clinicopathological characteristics of the CRC patients,and to clarify their clinical significances.Methods:The surgical tissue specimens from 77 patients with primary CRC were collected.Immunohistochemistry(IHC)method was used to detect the protein expressions of ANO1 and E-cadherin in CRC tissue;Spearman correlation analysis method was used to analyze the correlation between their expressions;PCR fluorescence probe method was used to detect the KRAS/NRAS mutations in CRC tissue;chi-square test or Fisher's exact probability method was used to analyze the relationships between the expressions of ANO1 and E-cadherin and clinicopathological characteristics of the CRC patients.Results:The IHC results showed that the positive expression rate of ANO1 in CRC tissue was 24.7％,and the positive expression rate of E-cadherin was 63.6％.The Spearman analysis results showed that the expressions of ANO1 and E-cadherin in CRC tissue were positively correlated(r=0.458,P<0.05).Compared with the patients with tumor located in rectum,the positive expression rate of ANO1 in cancer tissue of the CRC patients with tumor located in colon was significantly increased(χ2=5.499,P=0.019);compared with the patients with TNM stageⅢ-Ⅳ,the positive expression rate of ANO1 in cancer tissue of the CRC patients with TNM stageⅠ-Ⅱ was significantly increased(χ2=4.774,P=0.029);compared with the patients with lymphnode metastasis,the positive expression rate of ANO1 in the CRC patients without lymphnode metastasis was significantly increased(P=0.034).Compared with the CRC patients with T4 stage,the positive expression rate of E-cadherin in the CRC patients with T1-T3 stage was significantly increased(P=0.024).Compared with the CRC patients with p53 positive,Ki-67≥90％,PMS2 positive and KRAS wild-type,the positive expression rate of ANO1 in cancer tissue of the CRC patients with p53 negative,Ki-67<90％,PMS2 negative and KRAS mutant was significantly increased(P=0.031,P=0.036,P=0.048,P=0.028).Conclusion:The expressions of ANO1 and E-cadherin in primary CRC tissue of the patients are positively correlated;ANO1 and E-cadherin are associated with multiple clinicopathological characteristics of the patients;ANO1 and E-cadherin may be involved in the occurrence and progression of CRC.

Cerebral blood flow directly affects the metabolism of substances and neural activity in the brain, and is closely associated with the occurrence and development of cerebral small vessel disease (CSVD). Multiple studies have revealed that various imaging biomarkers in patients with CSVD, such as lacunar infarction, enlarged perivascular spaces, cerebral microbleeds, cerebral atrophy, and white matter hyperintensities, are closely associated with cerebral autoregulation (CA) function. Therefore, understanding the regulatory mechanism of CA in patients with CSVD is of great significance for delaying the further development of CSVD, improving cerebral ischemia and cognitive impairment. This article reviews the correlation and mechanism between CA and CSVD.

Objective To investigate the effect of splenectomy on the repair of full-thickness skin tissue defects,as well as the impact of different recovery times after splenectomy on the healing of skin tissue defects.Methods According to a random number table,39 8-week-old female C57 mice were randomly divided into three groups:sham surgery group(sham group,n=13),splenectomy group with 3 days of recovery(Spx3d group,n=13),and splenectomy group with 3 weeks of recovery(Spx3w group,n=13).Full-thickness skin defects were created on the backs of the mice in each group.The wound healing conditions at different times after skin defects were observed,and the wound healing rates after the injury were calculated.Peripheral blood cell analysis was performed on day 14 after the defect,and tissue samples from the wound area were taken for hematoxylin and eosin(HE)staining to observe the granulation tissue thickness at the defect site and the re-epithelialization rate.Masson's trichrome staining was used to observe the proportion of collagen fibers.Results After splenectomy and sham surgery,the mice recovered well without significant discomfort.From 1 to 14 days after the skin defect modeling,the wound areas of the mice in all three groups gradually decreased.Compared with sham group,the wound areas were smaller in Spx3d and Spx3w groups at 3,5 and 7 days after the injury,and the differences were statistically significant(P<0.05).The wound healing rates were also significantly higher(P<0.05).Moreover,at 3 days and 5 days after the injury,the wound healing rates of Spx3d group were significantly higher than those of Spx3w group(P<0.05 or P<0.01).The peripheral blood white blood cell(WBC)count in Spx3w group was significantly higher than that in sham group and Spx3d group(P<0.01).The platelet counts in both sham group and Spx3w group were significantly higher than that in Spx3d group(P<0.05).Additionally,the lymphocyte and neutrophil counts in Spx3w group were markedly higher than those in sham group(P<0.05).No statistically significant differences in red blood cell(RBC)counts were observed among the three groups(P>0.05).HE staining results showed that compared with sham group,the wound healing of the mice in Spx3d and Spx3w groups were better,and the thickness of the granulation tissue in Spx3d group were better than that in Spx3w group.At 7 days,the thickness of the granulation tissue in Spx3d and Spx3w groups was significantly higher than that in sham group(P<0.01,P<0.05)and the re-epithelialization rate in Spx3d group was significantly higher than that in sham group and Spx3w group(P<0.05).At 14 days,the re-epithelialization rates of Spx3d and Spx3w groups were significantly higher than those of sham group(P<0.05).The results of Masson's staining showed that the collagen fiber proportion in the wounds of Spx3d group at 7 and 14 days and that of Spx3w group at 14 days were significantly higher than that in sham group(P<0.05).Conclusion The healing of skin defects in mice is accelerated after splenectomy,and the recovery time after splenectomy has a certain effect on the healing of skin defects.

Objective:The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) .Methods:This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared.Results:①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD ( P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM ( R2=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion:sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.

Objective:To investigate the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation in patients with mild carotid artery stenosis.Methods:A retrospective study was conducted to select 30 cases of patients with unilateral mild carotid artery stenosis and moderate intensity aerobic exercise for more than 1 year in the Central Hospital of Dalian University of Technology from July 2022 to November 2023 as the exercise group (study group), and 30 cases of patients with unilateral mild carotid artery stenosis without exercise habits matched by age, gender and other factors as the non-exercise group (control group). Transcranial Doppler ultrasound (TCD) examination was performed in both groups, and the recumbent-upright-test, breath holding test and breath exchange test were performed to calculate the occurrence rate of "w" wave in recumbent-upright position, the slope of "w" wave in recubitus position, the change rate of pulse index (PI) before and after breath holding, resistance index (RI), breath holding index (BHI), and cerebral blood flow velocity before and after breath exchange. The blood pressure and heart rate difference in the recumbent-upright position were calculated, and the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation function in patients with mild carotid artery stenosis was evaluated by statistical analysis. The correlation analysis between the exercise years and BHI in the study group was carried out to explore the relationship between the exercise years and cerebrovascular reactivity.Results:The occurrence rate and slope of "w" wave in the study group were higher than those in the control group: 93.3%(28/30) vs. 86.7%(26/30), 2.27 ± 1.14 vs. 1.28 ± 0.23, 2.67 ± 0.63 vs. 1.41 ± 0.69, there were statistically significant ( P<0.05). The change rates of PI and RI before and after breath holding and ventilation in the study group were higher than those in the control group: 21.23 ± 7.67 vs. 13.89 ± 9.67, 14.62 ± 6.63 vs. 11.17 ± 1.78 and 26.26 ± 12.46 vs. 18.36 ± 12.13, 14.91 ± 4.91 vs. 10.83 ± 2.35, and the average cerebral blood flow velocity before and after ventilation was higher than that in the control group: (31.26 ± 4.92) cm/s vs. (24.89 ± 6.34) cm/s, there were statistically significant ( P<0.01). The exercise years of the study group was negatively correlated with the breath holding index. Conclusions:Moderate intensity exercise is associated with cerebral blood flow regulation in patients with mild carotid artery stenosis. Exercise years are negatively correlated with cerebral blood flow regulation. Impaired cerebral blood flow regulation may be one of the potential mechanisms of poor prognosis of stroke in carotid artery stenosis population.

Objective:To compare single-cell transcriptome sequencing data from skin samples of patients with atopic dermatitis (AD) and those from skin samples of healthy controls, and to investigate immunometabolic characteristics of inflammatory dendritic epidermal cells (IDECs) in skin lesions of patients with AD.Methods:An in-depth analysis was carried out on previously published single-cell sequencing data from 8 AD patients and 7 healthy controls in the Gene Expression Omnibus database (GSE 153760). Marker genes were used to screen out IDECs, and differentially expressed genes in IDECs between the two groups were analyzed. Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed on these differentially expressed genes, the "AddModuleScore" function in the Seurat package was used to evaluate the IDEC-involved inflammatory and metabolic pathways in the two groups, and Mann-Whitney rank sum test was used for statistical analysis; correlations between the IDEC-involved metabolic and inflammatory pathways were evaluated using the above scores and the "cor" and "cor.test" functions in R packages.Results:A large number of IDECs infiltrating the skin lesions of AD patients highly expressed Th2 chemokines (CCL17), antigen presentation-related genes (CD1B), endothelial growth-related genes (TYMP, AREG), inflammation-related genes (S100A8, S100A10, LGALS1), stromal fibrosis-related genes (MMP12, ADAM19), metabolism-related genes (LDHA, LIPA, GLUL), and danger signaling-related genes (HSPA1B, HSP90AA1, HSPB1, HSPH1). The activities of glucose energy metabolism, glycolytic metabolism, nucleotide metabolism, glutamate and glutamine metabolism, and amino acid metabolism were significantly upregulated in IDECs in AD patients, and were positively correlated with Th2 inflammation levels; the activities of oxidative phosphorylation and lipid metabolism were significantly downregulated in IDECs in AD patients, and the lipid metabolism level was negatively correlated with Th2 inflammation levels. Glutamine metabolism and glucose energy metabolism activities were positively correlated with Th22 inflammation levels; Th1 and Th17 inflammation levels were negatively correlated with the activities of pentose phosphate metabolism, nucleotide metabolism, glycolytic metabolism, and amino acid metabolism pathways.Conclusion:The inflammation- and metabolism-related genes were abnormally expressed in IDECs in skin lesions of AD patients, and activities of multiple metabolic pathways were markedly upregulated in IDECs, among which the glycolysis metabolism activity was mostly correlated with Th2 inflammation levels.

Objective Using the weighted gene co-expression network analysis(WGCNA)to explore the key genes of aging associated with Alzheimer's disease(AD).Methods GSE132903 was selected from GEO database as the analysis dataset.The differential expressed genes(DEGs)of AD were screened,and visualized with volcano and heat map.Aging and senescence-associated genes(ASAGs)were downloaded from MsigDB,Aging Altas and CellAge databases.WGCNA screened the gene modules with the highest correlation with AD,and genes of key modules subsequently performed with gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.AD age-related differential expressed genes(ARDEGs)were obtained by taking intersection genes of DEGs,key module genes of WGCNA and ASAGs.Protein-protein interaction(PPI)network analysis was performed using the STRING database to find key node genes.The co-expression networks and associated functions of key genes were analyzed using the GeneMANIA database.The key genes were validated in Alzdata database.Results 226 DEGs,606 ASAGs and 8 ARDEGs were obtained.The top 5 key genes selected by PPI were SYP,STXBP1,VAMP2,CPLX1 and STX1A.Alzdata database verified that the expressions of 5 key genes in other brain regions of AD were down-regulated,except for no significant changes of VAMP2 in hippocampus and STXBP1 in frontal cortex,as well as no expression of CPLX1 in frontal cortex.The differential expression of VAMP2,STXBP1 and STX1A appeared in the early stage of AD,and CPLX1 was related to the pathological process of Tau.SYP and STXBP1 were related to the pathological processes of amyloid β-protein and Tau.Conclusion SYP,STXBP1,VAMP2,CPLX1 and STX1A are ARDEGs,which are expected to be potential diagnostic and therapeutic targets for AD.

Cerebral hyperperfusion syndrome (CHS) is a rare but serious complication after cerebral revascularization, which may lead to catastrophic consequences. The mechanism of CHS is not fully understood, and it may be related to cerebral autoregulation dysfunction and the increase of blood pressure after operation. Timely detection and treatment of cerebral hyperperfusion can avoid CHS. This article reviews the pathogenesis, diagnosis, clinical manifestations, prevention and treatment of CHS.

"Shaoyang as the pivot"is one of the important concepts in the theory of traditional Chinese medicine.It is believed that shaoyang is located between half exterior and half interior,which reaches the muscular striae and the exterior and connects with the internal organs,and plays the role of promoting qi movement,regulating water channel and distributing ministerial fire.The dysfunction of shaoyang pivot leads to the disorder of qi movement,abnormal water metabolism,and stagnation or hyperactivity of ministerial fire.Cholinergic urticaria is a special type of urticaria caused by the disorder of cholinergic nerve conduction,which has a long course of disease and is difficult to be cured.According to the clinical characteristics of the disease,Professor SUI Dao-Shun believes that the dysfunction of shaoyang pivot is the core pathogenesis of cholinergic urticaria.Emotional disorders lead to the dysfunction of pivot,and then cause the disordered flow of qi and fluid and internal disturbance of hyperactive ministerial fire,which induce the disharmony between nutritive qi and defensive qi,and the failure of being against the pathogens.Finally,wind pathogen attacks the skin and muscular striae and becomes latent,and results in cholinergic urticaria.For the treatment of cholinergic urticaria,Chaihu Guizhi Decoction can be used as the basic prescription to harmonize shaoyang,expel pathogens and release exterior.Corresponding modification of herbal medicines should be performed for various syndromes caused by the dysfunction of shaoyang pivot such as qi stagnation,dampness retention and heat stagnation during the clinical application.The prevention and treatment of cholinergic urticaria based on the theory of shaoyang as the pivot can provide thoughts for the clinical treatment of cholinergic urticaria.

Objective To study the use of phospholipase A2(PLA2)to open blood brain barrier(BBB)by affecting the physiological barrier function and promote the antidote drug asoxime(HI-6)to take effect in brain,providing a new research idea for the treatment of central nervous system organophosphorus poisoning.Methods The stability of the complex of PLA2-HI-6 was characterized through methods such as release and stability experiments.The cerebral delivery ability of the complex was evaluated through brain tissue FLU fluorescence pathology.The effect of PLA2 on cell membrane permeability was evaluated by observation with propidium iodide(PI)staining.The mouse model of soman poisoning was established to evaluate cerebral effects of the complex against soman central poisoning:(1)measuring the reactivation rate of mouse brain acetylcholinesterase(AChE);(2)observing pathological sections of mouse brain tissues;(3)calculating the survival time of mice in different groups.The safety of PLA2 was evaluated at both cellular and animal levels.Results Releasing and stability test results showed that the addition of PLA2 didn't affect the release and degradation of HI-6.PLA2 helped FLU transport into brain tissues,demonstrating excellent central delivery capability.The complex of PLA2-H1-6 significantly increased the reactivation rate of AChE in the brain of poisoned mice to 50％,about 12 times higher than that treated by HI-6 alone.Pathological results of mouse brain tissue showed that the complex effectively counteracted the cerebral nervous system damage caused by organophosphorus poisoning,significantly prolonged the survival time of mice at three times the lethal dose,and significantly alleviated symptoms of central toxicity.Research on delivery mechanisms found that complex achieved central delivery by increasing the permeability of the cell membrane to crossing the cell.Safety tests at the cellular and animal levels showed that the dosage of PLA2 used in this study was safe and reliable,and did not cause any adverse reactions.Conclusion By using PLA2 as an open material,combined with the therapeutic drug of HI-6,a complexcapable of effectively penetrating the BBB was successfully constructed.This complex has a certain central targeting ability and significantly improves the reactivation rate of AChE in the brain after organophosphorus poisoning,whichprovides a referencefor solving the difficult problem of enzyme reactivation incentral nervous system organophosphorus poisoning.