Objectives To investigate the characteristics of changes in serum metabolic profile before and after resection of carcinoma tissues to establish a disease distinguishing model,to analyze the changing trend of characteristic metabolites,and to determine the molecular mechanism and potential clinical value of characteristic metabolic markers for HBV-related liver cancer.Methods Ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the serum metabolites of 15 patients with hepatocellular carcinoma (HCC) before and after partial hepatectomy and on 25 healthy volunteers.The pattern recognition method and nonparametric test analyzes were used to analyze the data and to identify the specific metabolites and their changes after resection of carcinoma tissues.Results We established the principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) disease distinguishing model for HCC patients before and after operation as against the healthy volunteers.To distinguish between the liver cancer group and the normal control group,27 characteristic metabolites were selected from the patients before and after resection of carcinoma tissues.Eight moved towards the normal control after resection of carcinoma tissues.This indicated that liver carcinoma was an important impacting factor for these metabolites.Finally,7 metabolites were identified,and these metabolites had high diagnostic value as shown on ROC curves.Conclusions Through serum metabolic profiling of patients before and after resection of carcinoma tissues,a high correlation between metabolism and hepatocellular carcinoma was found.Researches on endogenous metabolites and pathways in liver diseases will provide a better understanding of the molecular mechanisms and provide further directions for clinical diagnosis and treatment.

Objective: To compare the therapeutic effects of two different moxibustion methods both with tai-yi moxa stick in treating primary dysmenorrhea. ＜br> Methods: Forty-three patients were randomized into two groups by the random number table according to their treatment orders. The causalgic group was intervened by causalgic stimulation with tai-yi moxa stick while the tepid group was treated by mild thermal stimulation with tai-yi moxa stick. Shiqizhui (EX-B 8) was selected for both groups. Visual analogue scale (VAS) was used for observation before and during the treatment by every 10 min to compare the clinical efficacies between the two groups. ＜br> Results: Before treatment, there was no statistically significant difference in pain intensity between the two groups (P>0.05). After treatment, both groups achieved significant improvements in pain intensity (P＜0.05), but the inter-group difference in pain intensity was still statistically insignificant (P>0.05), but the difference was enlarged comparing with that before treatment. The pain relief during the first 10 min of treatment was slower in the causalgic group than that in the tepid group. However, during the later 20 min, the pain relief in the calsalgia group gradually outpaced that in the tepid group. ＜br> Conclusion: The two moxibustion methods with tai-yi moxa stick both have a good instant analgesic effect in treating primary dysmenorrhea. For patients with primary dysmenorrhea, if 30 min is regarded as the treatment time, mild stimulation was suggested to be used for the first 10 min, and causalgic stimulation for the later 20 min to achieve a better curative effect.

Objective:To explore the tumor microenvironment (TME) module associated with pancreatic ductal adenocarcinoma (PDAC) and identify prognostic biomarkers and potential immunotherapeutic targets.Methods:The genetic expression profile data were collected and selected from a dataset of 142 PDAC patients in The Cancer Genome Altas (TCGA) database and 2 microarray datasets (GSE2150, GSE62452) of 168 PDAC patients in Gene Expression Omnibus (GEO) database, and the cell type enrichment analysis of PDAC gene expression data was analyzed by xCell network tool. According to the median cell enrichment score, 142 patients from TCGA were divided into high score group and low score group, and the cell types with prognostic value were determined by univariate survival analysis and validated by GEO datasets. According to the cell type, the differential expression gene analysis and univariate survival analysis were performed to determine the prognosis related differential expression genes (DEGs), and the prognostic DEGs were analyzed by function enrichment analysis and protein-protein interaction (PPI) network analysis. At the same time, GEO dataset was used to verify the prognosis related DEGs of TCGA datasets. Finally, TISIDB database was searched for the common DEGs of TCGA and GEO database, and its correlation with immune system was analyzed.Results:Cell type enrichment analysis showed that Th1 cell and keratinocyte had the same prognostic value in both TCGA and GEO dataset; the overall survival rate of patients with high score was lower than that of those with low score, and the differences were statistically significant (all P values <0.05). 216 prognosis related DEGs were identified, and the results of functional enrichment showed that 9 of the 21 biological process items were closely related to the immune process, and 4 of the 5 KEGG (Kyoto Encyclopedia Of Genes and Genomes) pathways were closely related to the immune process. Through PPI network analysis, CCR7, CD 27, CD 5, CXCL13, ZAP70, MS4A1 and CCL19 were proved to be possibly closely associated with central genes. Through the validation of GEO datasets, there were 15 DEGs with similar prognostic value in GEO and TCGA datasets, which was searched in TISIDB dataset, and the result showed that GIMAP7 was closely related with the immune process of PDAC. Conclusions:A group of 216 TME genes and 7 central genes related to the prognosis of PDAC were identified, and 5 potential targets for immunotherapy of PDAC were provided, including CCR7, CCL19, CD 27, CXCL13 and GIMAP7.

OBJECTIVE To explore mecha-nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net-work pharmacology combined with in vitro experi-ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data-bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100 μ mol·L-1)on P-gp activity were monitored in hCMEC/D3in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans-mission regulation,neurotransmitter receptor activity,proteinkinaseregulationactivity,G protein-coupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig-naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi-cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu-lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro-tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer-ence basis for further exploration of the mecha-nisms of imperatorin on regulating P-gp in BBB.

Objective: To explore the glycemic control of newly-diagnosed type 2 diabetes with different levels of baseline body mass index (BMI) after 6 months treatment under the standardized metabolic disease management model. Methods: (1) 163 patients of newly-diagnosed type 2 diabetes were divided into normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI≥28 kg/m²) groups according to baseline BMI, the blood glucose and lipids levels were compared among 3 groups. (2) The blood glucose levels were compared among 3 groups after 6 months of standardized management. (3) The overweight and obese patients were divided into group weight loss≥5% and group weight loss<5% or weight gain in 6 months. The blood glucose levels were compared. Results: (1) At baseline, overweight and obese groups had higher homeostasis model assessment for insulin resistance and lower high density lipoprotein-cholesterol compared with normal weight group. (2) After 6 months of treatment, HbA_1C and HbA_1C reduction showed no difference among 3 groups (normal, overweight and obese) after adjusted by baseline HbA_1C. The rate of HbA_1C<7% among 3 groups were 77.78%, 83.95%, and 80.43% (P>0.05). (3) After 6 months of treatment, 32.28% overweight and obese patients lost weight by ≥ 5%, while HbA_1Cand HbA_1Creduction showed no difference between 2 groups (weight loss≥5% and weight gain or weight loss<5%) after adjusted by baseline HbA_1C. Both groups achieved good glycemic control [(6.27±1.38 vs 6.43±0.66)%], but have no significantly(P>0.05). Group weight loss≥5% had better glucose control (92.68% vs 77.91%, P<0.05). Conclusions As BMI increased, insulin resistance and lipid disorders were more serious in newly-diagnosed type 2 diabetes. After 6 months of standardized metabolic management, newly-diagnosed type 2 diabetes with different baseline BMI and weight changes both achieved good glycemic control. In addition, patients losing weight equal to or more than 5% achieved higher attainment of HbA_1C targets.

Lymphocytic hypophysitis(LYH) is a rare autoimmune inflammatory disorder of the pituitary gland, usually affecting young women in late pregnancy or postpartum period. To enhance the knowledge of LYH, herein we reported a case of LYH in a female during postpartum who presented with pituitary crisis.

Objective:To observe the extent of brain edema caused by severe cut injury and the protective role of umbilical cord mesenchymal stem cells (UC-MSCs).Methods:A total of 90 female C57L mice were selected and the models of severe cut injury were prepared with surgical blade. According to the random number table, the animals were divided into control group (20 mice), cut group (20 mice), interleukin-6 antibody (IL-6-AB) before cut group (administered IL-6-AB at 18 hours before cut, 15 mice), IL-6-AB after cut group (administered IL-6-AB at 1 hour after cut, 15 mice) and UC-MSCs group (20 mice). The extent of brain edema was detected, the level of IL-6 in brain tissue by ELISA method and the expression of aquaporin-4 (AQP-4) by Western blot assay.Results:Brain water content test showed brain edema in cut group was (81.5±1.8)%, significantly higher than (77.1±2.4)% in control group ( P<0.05). Compared with cut group, brain edema in UC-MSCs group [(76.8±2.4)%] and IL-6-AB before cut group [(76.2±2.9)%] were significantly decreased ( P<0.05), while that in IL-6-AB after cut group [(82.4±1.7)%] was little decreased ( P>0.05). ELISA showed the level of IL-6 in cut group was significantly increased in mouse brain [(16.6±1.3)pg/ml], when compared with control group [(10.3±0.3)pg/ml] ( P<0.01). Compared with cut group, the levels of IL-6 in UC-MSCs group [(10.7±0.6)pg/ml] and IL-6-AB before cut group [(10.1±0.4)pg/ml] were significantly decreased ( P<0.01), while that in IL-6-AB after cut group [(14.9±1.2)pg/ml] was little decreased in mouse brain ( P>0.05). Western blot assay showed that compared with control group (1.0±0.1), the expression of AQP-4 in cut group (2.4±0.5) was significantly increased in mouse brain ( P<0.01). Compared with cut group, the expression of AQP-4 in UC-MSCs group (1.2±0.3) and IL-6-AB before cut group (1.0±0.1) were significantly decreased ( P<0.01), while that in IL-6-AB after cut group (2.3±0.3) was little decreased in mouse brain ( P>0.05). Conclusions:Severe cut injury can increase brain water content and eventually lead to brain edema through upregulating the levels of IL-6 and AQP-4 protein in the brain. Moreover, UC-MSCs effectively prevent the formation of brain edema by inhibiting the above effects.

BACKGROUNDCushing's disease (CD) presents a remarkable preponderance in female gender, and a significant minority of patients with CD presented with negative magnetic resonance imaging (MRI) findings. The aim of this study was to evaluate gender-related and MRI classification-related differences in clinical and biochemical characteristics of CD.

METHODSWe retrospectively studied 169 patients with CD, comprising 132 females and 37 males, and 33 patients had no visible adenoma on MRI.

RESULTSWe observed that male and MRI-positive patients presented with high adrenocorticotropic hormone (ACTH) values (P < 0.05). Female patients presented with higher prevalence of hirsutism and hyperpigmentation and lower prevalence of purple striae (P < 0.05). The prevalence of buffalo-hump and hypertension was greater in MRI-negative patients (P < 0.05). In addition, male patients with CD presented at a younger age compared with females (P < 0.05). Patients with fatigue and hypokalaemia presented significantly higher urinary-free cortisol, ACTH and cortisol levels compared with patients without these symptoms (P < 0.05). The prevalence of LH reduction, hyper total cholesterol (TC) and hyper low-density lipoprotein was more frequent in MRI-positive patients (P < 0.05). Hyper-TC levels and PRL reduction were more frequent in males (P < 0.05). T3, T4 and FT3 levels negatively correlated with age at diagnosis (r = -0.310, P < 0.01; r = -0.191, P < 0.05; r = -0.216, P < 0.05). T3, T4, FT3 and FT4 levels significantly negatively correlated with 8-am plasma cortisol levels (r = -0.328, P < 0.01; r = -0.195, P < 0.05; r = -0.333, P < 0.01; r = -0.180, P < 0.05). Females presented higher total protein level (P < 0.01) and lower blood urea nitrogen and serum creatinine levels (P < 0.01), compared with male patients.

CONCLUSIONSCarefulness and caution are required in all patients with CD, because of the complexity of clinical and biochemical characteristics in CD patients of different gender and MRI classification, particularly male patients and MRI-negative patients.

Adolescent ; Adult ; Aged ; Dyslipidemias ; diagnosis ; Female ; Humans ; Hypertension ; diagnosis ; Hypokalemia ; diagnosis ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pituitary ACTH Hypersecretion ; complications ; diagnosis ; Retrospective Studies ; Sex Factors ; Young Adult

ObjectiveTo investigate the abnormal changes of gray matter structure covariant network in post-stroke aphasia (PSA) patients. MethodsFrom June, 2019 to March, 2022, 15 PSA patients (patient group) from Dongzhimen Hospital, Beijing University of Chinese Medicine and Beijing Bo'ai Hospital were recruited, as well as 15 healthy subjects (control group). Their brain structure magnetic resonance imaging data were collected. The brain covariant network was constructed based on gray matter volume correlation, and graph theory analysis method was used to evaluate the global and node network level topology properties of structural covariant network. The differences of gray matter covariant network properties between patients and controls were compared. ResultsThere was no significant difference in the global network level topology properties between two groups (P > 0.05). At the nodal level, compared with the control group, the betweenness decreased in the right middle frontal gyrus, right posterior cingulate gyrus, right amygdala, left middle occipital gyrus, and increased in the right inferior frontal gyrus and the right suboccipital gyrus of the insula operculum (P < 0.05); the node degree decreased in the left superior frontal gyrus, left anterior cingulate and paracingulate gyrus, left hippocampus and left amygdala, while it increased in the right inferior frontal gyrus, left supplementary motor area, right superior occipital gyrus, right inferior occipital gyrus, and right lentiform pallidus (P < 0.05); the node efficiency decreased in the left anterior cingulate and paracingulate gyrus, left hippocampus, left amygdala, left temporal pole: superior temporal gyrus, and increased in the inferior frontal gyrus of right insula, left supplementary motor area and right suboccipital gyrus (P < 0.05). ConclusionThe abnormal reduction of node network properties in some brain regions in the left hemisphere of PSA patients may be a characteristic structural covariation pattern, and there may be some compensation in the right hemisphere of the structural network in some brain regions.