ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

Objective:To explore the relationship between hemoglobin variability (Hb-var) and risk of all-cause death and cardiovascular death in patients with peritoneal dialysis (PD), and to provide basis for reducing the risk of death in PD patients.Methods:It was a multicenter retrospective cohort study. The clinical data of regular PD patients from Nanfang Hospital of Southern Medical University, Shunde Hospital of Southern Medical University, Foshan First People's Hospital and Ganzhou People's Hospital from July 1, 2008 to December 31, 2019 were collected. Hb-var was calculated based on hemoglobin at baseline before PD and in the first year after PD. The patients were divided into low Hb-var group, moderate Hb-var group and high Hb-var group according to the tertiles of first year Hb-var, and the differences of baseline clinical data among three groups were compared. Follow-up endpoints included death, transfer to hemodialysis, transfer to kidney transplantation, transfer to other centers, loss of follow-up, or on December 31, 2021. Cox regression analysis model was used to analyze the association of the first-year Hb-var with all-cause death and cardiovascular death. Fine-Gray competitive risk regression model was used to evaluate the impact of competitive events on mortality risk.Results:A total of 1 562 patients with PD were included in the study, aged (47.6±13.8) years old, with 821 males (52.6%) and baseline hemoglobin of 81 (69, 94) g/L. Hb-var in the first year of PD was 26.6 (16.7, 40.3) g/L. There were statistically significant differences in age, body mass index, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, intact parathyroid hormone and the proportion of renin-angiotensin system inhibitors among low Hb-var group (<20.0 g/L), moderate Hb-var group (20.0-35.5 g/L) and high Hb-var group (≥35.5 g/L, all P<0.05). The follow-up time was 33 (19, 51) months, and 208 patients (13.3%) died, among which 111 patients (53.4%) died of cardiovascular death. Multivariate Cox regression analysis showed that the higher Hb-var in the first year, the lower the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.018) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) in PD patients. Compared with low Hb-var group, the risk of all-cause death ( HR=0.56, 95% CI 0.37-0.82, P=0.003) and cardiovascular death ( HR=0.54, 95% CI 0.31-0.95, P=0.032) was lowest in the high Hb-var group. The competitive risk regression model analysis showed that Hb-var in the first year was still negatively correlated with the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.039). Conclusion:High Hb-var in the first year is associated with low risk of all-cause death and cardiovascular death in PD patients with severe anemia at baseline.

Objective: To analyze the prognosis and risk factors of lung metastasis of patients with adenoid cystic carcinoma(ACC) of head and neck. Methods: A retrospective study was conducted. The data of 157 patients with ACC of head and neck treated in Beijing Tongren Hospital, Capital Medical University from January 2014 to October 2020 were collected, including 72 males and 85 females, with onset age between 14 and 72 years old. According to whether lung metastasis occurred, the patients were divided into lung metastasis group (88 cases) and non-pulmonary metastasis group (69 cases). Kaplan-Meier method was used to calculate the overall survival rate and progression-free survival rate using SPSS 26.0 software. Log-rank test was used to evaluate statistically relevant clinicopathological factors. Cox proportional risk model was used in multivariate analysis for the factors affecting the lung metastasis-free survival using R Studio 1.2.5042. Results: The 3-year and 5-year overall survival rates were 91.5% and 85.2%, respectively. The 3-year and 5-year progression-free survival rates were 57.7% and 34.3%, respectively. Univariate analysis showed that primary site, histological grade, high-grade transformation, Ki-67, T stage, and lymph node status were the risk factors for lung metastasis (χ²=11.78, 10.41, 4.06, 4.71, 5.37, 16.20, respectively, all P<0.05). Multivariate analysis showed independent risk factors for lung metastasis, including submandibular gland and sublingual gland (HR=3.53, 95%CI: 1.19-10.46, P<0.05), T3-4 stage (HR=3.09, 95%CI: 1.54-6.23, P<0.05), and Grade Ⅱ-Ⅲ grade (HR=2.47, 95%CI: 1.26-4.86,P<0.05). Conclusion: Distant metastasis, mainly pulmonary metastasis, affects the long-term prognosis of patients with ACC significantly. Primary site, T stage and histopathological grade can be used as the predictors for the risk of lung metastasis.
Adolescent ; Adult ; Aged ; Carcinoma, Adenoid Cystic ; Female ; Humans ; Lung/pathology* ; Lung Neoplasms/secondary* ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; Young Adult

Objective To investigate the pollution level of 9,10-anthraquinone in teas sold in Wuhan, and to assess the dietary exposure of 9,10-anthraquinone ingested through tea. Methods The content of 9,10-anthraquinone in teas collected from local tea markets in Wuhan was analyzed by GC-MS/MS. Results 9,10-anthraquinone was detected in all 36 tea samples with a concentration ranging from 0.0080 mg/kg to 0.137 mg/kg. The standard limit for 9,10-anthraquinone has not yet been set in China. Referring to EU standards, the total over-standard rate was 86.11% (31/36). Generally, the concentration of residual 9,10-anthraquinone was higher in highly fermented teas. The highest average concentration of residual 9,10-anthraquinone was found in fully/post-fermented tea (0.0762 mg/kg), and the over-standard rate was 100%. The second highest was in semi-fermented tea (0.0452 mg/kg), and the over-standard rate was 86.7%. The concentration of 9,10-anthraquinone in non-fermented tea was 0.0262 mg/kg, and the over-standard rate was 42.9%. According to people^’s tea-drinking habits, tea samples were brewed with boiling water（1:50）for 5 minutes, and the concentration of 9,10-anthraquinone in tea soup was 0.0004 mg/kg～0.01 mg/kg, with an average leaching rate of 7.2%. The average daily intake exposure of tea for an adult was 0.0551μg/kg bw/day. Conclusion There was a certain degree of 9,10-anthraquinone pollution in the teas sold in Wuhan, and the rate exceeding the standard was high. Since the acceptable daily intake (ADI) for 9,10-anthraquinone has not been established, it is impossible to assess the health risks of 9,10-anthraquinone ingested through tea.

OBJECTIVE: To explore the molecular basis for an A subtype of the ABO blood group. METHODS: The forward and reverse typing of the ABO blood group were identified by gel card and test tube methods. The ABO gene of the patient was detected by PCR-sequence specific primer (PCR-SSP). Exons 1 to 7 of the ABO gene was amplified by PCR and sequenced. The ABO gene was also subjected to subclone sequencing for haplotype analysis. RESULTS: The patient's red cells showed weak agglutination with anti-A but non-agglutination with anti-B. The patient's serum showed 1+ agglutination with A cells and 4+ agglutination with B cells. Based on above serological characteristics, the patient was defined as Aw subtype of the ABO blood group. Sequencing analysis showed that the patient was heterozygous for c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.297A>G, c.467C>T, c.543G>C, c.646T>A, c.681G>A, c.771C>T, c.829G>A, in addition with a c.261G deletion. Combined with the result of subclone sequencing, the ABO genotype of the patient was determined as ABO*AW.33. new/O.01.02, which harbored c.467C>T and c.543G>C variants compared with ABO*A1.01 and c.543G>C variant compared with ABO*A1.02. The novel allele has been submitted to GenBank with an accession number of MK302122. CONCLUSION A novel allele of Aw33 subtype has been identified with its GTA transferase gene harboring c.467C>T and c.543G>C variants compared with A1.01.
ABO Blood-Group System ; genetics ; Alleles ; Exons ; genetics ; Genotype ; Humans ; Phenotype

Objective:To investigate the effect of trans-activation of transcription (Tat) lysine 41 on HIV-1 transcription and compare the effect of HIV-1 subtypes B and C.Methods:The effects of wildtype Tat, Tat K41A and Tat K41R mutants on HIV-1 transcription were assessed by luciferase assay, and the differences of Tat K41 effect were compared in subtypes B and C viruses. Next, immunoprecipitation (IP) assay was used to detect whether Tat K41 of HIV-1 clades B and C affects the interaction between Tat and SIRT1. Finally, Western blot was used to detect whether K41 of Tat B and Tat C affects the acetylation level of p65 K310 in the nucleus.Results:Mutants of subtype C Tat K41 significantly inhibited Tat transactivation, reduced the interaction between SIRT1 and Tat C and decreased the level of p65 K310ac in the nucleus compared with wildtype of subtype C Tat, but there were no significant changes in subtype B Tat.Conclusions:Subtype C Tat K41 plays a vital role in HIV-1 transcription.

Objective: To determine the HIV infection of a 13-year-old leukemia patient Wei using molecular tracing technique. Methods: Three blood samples were collected from the persons who were associated with HIV positive blood donation member Lang. The viral load was tested and pol gene was sequenced and analyzed. At the same time using HyPhy2.2.4 and Cytoscape 3.6.1 to establish the molecular network with these 3 samples sequences and other HIV subtypes sequences obtained from Luzhou. Results: The HIV-1 viral load test result of the three patients were: Lang 933 CPS /ml (treated, blood donor), Wei (blood recipitent) 89 813 CPS /ml, Deng (blood recipitent) 85 158 CPS /ml. The subtype of HIV-1 of these three samples were all recombinant HIV CRF01_AE, and the pol gene similarity was 98.8% (Lang and Wei), 99.7% (Lang and Deng), and 99.1% (Wei and Deng), respectively. The gene sequences of the three samples were linked into clusters (the gene distance was less than 0.004). Conclusions The patient Wei with leukemia was infected with HIV-1 due to blood transfusion during the seroconversion period, and the three patients were more likely to be infected with the same HIV-1 strain. It is necessary to popularize the use of high-sensitivity nucleic acid detection method in blood collection and supply institutions, which can effectively improve the safety of blood use.

Identifying data-driven biotypes of major depressive disorder (MDD) has promise for the clarification of diagnostic heterogeneity. However, few studies have focused on white-matter abnormalities for MDD subtyping. This study included 116 patients with MDD and 118 demographically-matched healthy controls assessed by diffusion tensor imaging and neurocognitive evaluation. Hierarchical clustering was applied to the major fiber tracts, in conjunction with tract-based spatial statistics, to reveal white-matter alterations associated with MDD. Clinical and neurocognitive differences were compared between identified subgroups and healthy controls. With fractional anisotropy extracted from 20 fiber tracts, cluster analysis revealed 3 subgroups based on the patterns of abnormalities. Patients in each subgroup versus healthy controls showed a stepwise pattern of white-matter alterations as follows: subgroup 1 (25.9% of patient sample), widespread white-matter disruption; subgroup 2 (43.1% of patient sample), intermediate and more localized abnormalities in aspects of the corpus callosum and left cingulate; and subgroup 3 (31.0% of patient sample), possible mild alterations, but no statistically significant tract disruption after controlling for family-wise error. The neurocognitive impairment in each subgroup accompanied the white-matter alterations: subgroup 1, deficits in sustained attention and delayed memory; subgroup 2, dysfunction in delayed memory; and subgroup 3, no significant deficits. Three subtypes of white-matter abnormality exist in individuals with major depression, those having widespread abnormalities suffering more neurocognitive impairments, which may provide evidence for parsing the heterogeneity of the disorder and help optimize type-specific treatment approaches.

A 3-year-old female proband presented with patchy follicular keratotic papules on the hairless scalp after birth. At about the age of 2 years, sparse hairs of non-uniform thickness began to grow, but they fell out intermittently and were broken easily. Some eyebrows and eyelashes of different lengths fell out or were broken. Physical examination revealed good condition of nutrition, normal height, weight and intelligence, with no obvious abnormalities in other systems. Skin examination showed sparse and broken hairs with follicular keratotic papules on the vertex and occiput. Teeth, nails, toenails and sweat glands were normal. Dermoscopy, optical microscopy and scanning electron microscopy all showed that affected hairs gave a beaded appearance. Gene sequencing showed that the proband carried heterozygous deletions of exons 2-16 in the desmoglein 4 (DSG4) gene, and a heterozygous mutation c.574T>C (p.S192p) (NM-177986) in the DSG4 gene, which were inherited from her father and mother respectively. None of the above mutations in the DSG4 gene were found in 100 healthy controls. According to the gene sequencing results and clinical phenotype, the patient was finally diagnosed with autosomal recessive hereditary monilethrix, and the c.574T>C mutation and heterozygous deletions of exons 2-16 of the DSG4 gene may contribute to autosomal recessive hereditary monilethrix in the child.

Objective To investigate the prognostic value of the texture analysis contrast-enhanced MR imaging (DCE-MRI) in predicting microvascular invasion in hepatocellular carcinoma (HCC) before operation. Methods Sixty patients with HCC confirmed by pathology in the Chinese Academy Medical Sciences from January 2014 to December 2016,were enrolled in our study retrospectively.According to the post-operative pathology, the patients were divided into positive microvascular invation[MVI(+)]group including 30 patients, and negative MVI[MVI(-)] group including 30 patients. All patients underwent normal MR and DCE-MRI before surgery.Sixty seven texture features were extracted from the original data of arterial phase (AP) and portal venous phase (PVP) of DCE-MRI. All data were calculated by using Omni-Kinetics(OK)software of the United States.The difference between MVI(+)group and MVI(-)group was statistically significant using the independent sample t test. The identified methods of the DCE-MR texture features in predicting MVI adopted the principal component analysis (PCA) and the establishing prediction model including dimensionality reduction, modeling, prediction and verification. The model was established by logistic regression method. According to the histopathology, 80% data of AP and PVP were used as training group[48 cases,MVI(+)and MVI(-)group 24 cases respectively],20% as validation group [12 cases, MVI(+) and MVI(-) group 6 cases respectively]. The DCE-MRI images of AP and PVP were modeled and cross-referenced respectively, and the diagnostic efficiency of ROC evaluation model was adopted. Results There were 15 significant different texture features of the AP and three significant different texture features of the PVP between MVI(+) group and MVI(-) group respectively. The PCA method extracted the important DCE-MRI texture features and analyzed the 15 features of AP.The UPP and energy showed a good correlation(r>0.90),therefore the UPP were removed.Fourteen texture features were analyzed using the PCA method.There were four important texture features including the GLCM Correlation, Hara Variance, GLCM sum Variance and GLCM sum Entropy in the AP. Moreover, there were three important texture features including GLCM difference Entropy, Long Run Low Grey Level Emphasis and GLCM difference Variance in the PVP.Through the prediction model was established and crossly validated. There were three significant different texture features in the AP of DCE-MRI,including GLCM Correlation, GLCM Contrast and GLCM sum Entropy.And there were two significant different texture features in the PVP of DCE-MRI,including GLCM difference Variance and Long Run Low Grey Level Emphasis.In the training and validation group,the areas under the ROC of the AP model and PVP model were 0.774,0.681,0.889 and 0.611 respectively.The diagnosed accuracy rate of the AP model(83.30%,10/12)was higher than that of the PVP model(42.00%,5/12).Conclusion The DCE-MRI texture analysis technique could predict the MVI of HCC before operation,and the predictive accuracy of the AP texture feature was higher.