A 27-year-old male was admitted to the Xijing Hospital in August 2018 due to unprovoked severe thoracodynia with palpitations, shortness of breath and chest tightness. Computed tomography angiography showed a type A aortic dissection. Genetic testing based on next-generation sequencing for 15 genes associated with hereditary aortic diseases and Sanger sequencing validation revealed a heterozygous missense mutation c.998G>T (p.Gly333Val) in the COL3A1 gene. Sanger sequencing verification of family members confirmed that the mutation c.998G>T co-segregated with the patient′s phenotype in this family. That mutation was classified as "likely pathogenic" according to American College of Medical Genetics and Genomics standards and guidelines for genetic variant classification. Carriers of this mutation can be definitively diagnosed with "vascular Ehlers-Danlos syndrome". After the diagnosis was clarified, symptomatic treatment was given to the patient, but the disease progressed rapidly. The patient discontinued treatment and died shortly after being discharged. In this study, we found a new variant in the COL3A1 gene, expanding the mutation spectrum of this gene.

Objective:To investigate the relationship between serum soluble CD155 (sCD155), soluble CD163 (sCD163) and chemotherapy efficacy and prognosis in patients with diffuse large B-cell lymphoma (DLBCL).Methods:A total of 126 patients with DLBCL admitted to Handan Central Hospital from May 2018 to May 2020 (DLBCL group) and 126 healthy subjects (control group) were prospectively selected to compare serum sCD155 and sCD163 levels. According to the chemotherapy effect of DLBCL patients, they were divided into effective group and ineffective group, and the serum sCD155 and sCD163 levels were compared before and after treatment. The effective rate of chemotherapy in patients with different serum sCD155 and sCD163 levels was compared. Kaplan-Meier method was used to analyze the relationship between serum sCD155 and sCD163 levels and 3-year overall survival (OS) and progression-free survival (PFS) of DLBCL patients. Cox proportional risk regression model was used to analyze the prognostic factors of DLBCL patients.Results:The serum levels of sCD155 and sCD163 in DLBCL group were higher than those in control group before treatment (all P<0.05). The effective rate of chemotherapy in 126 DLBCL patients in this group was 69.8%(88/126). Compared with the effective group, the serum levels of sCD155 and sCD163 were higher in the ineffective group before and after treatment (all P<0.05). Compared with before treatment, serum sCD155 and sCD163 levels in the effective group were decreased after treatment (all P<0.05). The effective rate of DLBCL patients in sCD155 and sCD163 high level groups was lower than that in sCD155 and sCD163 low level groups (all P<0.05). Kaplan-Meier analysis showed that the 3-year OS and PFS of DLBCL patients in the low level group of sCD155 and sCD163 were higher than those in the high level group (all P<0.05). The high level of sCD155 and sCD163 were independent risk factors for 3-year PFS and OS in DLBCL patients (all P<0.05). Conclusions:Abnormal levels of serum sCD155 and sCD163 in DLBCL patients may reduce the efficacy of chemotherapy and lead to poor prognosis.

Atherosclerosis is a chronic vascular inflammatory disease caused by abnormal lipid metabolism.The formation of lipid-rich foam cells acts as the initial trigger for development of atherosclerotic lesions.Recent studies have shown that lipophagy,a form of selective autophagy,can selectively degrade lipid droplets stored intracellularly and promote cholesterol efflux through the autophagic lysosomal pathway.As a result,intracellular lipid accumulation is re-duced and foaming is inhibited,making lipophagy a potential new target for current anti-atherosclerosis therapy.This arti-cle reviews the crucial role and molecular mechanism of lipophagy in the link between lipid metabolism and atherosclero-sis.Its objective is to outline the regulatory mechanism of lipophagy and present fresh insights for the treatment of athero-sclerotic diseases.

Objective:To preliminarily evaluate the immunogenicity and efficacy of two novel tuberculosis vaccine candidates (a fusion multicomponent protein EPDPA015f and a mixed multicomponent protein EPDPA015m) and to provide a new antigen combination for the development of tuberculosis vaccines.Methods:Recombinant plasmids for the expression of EPDPA015f and EPDPA015m proteins were constructed. Six-week-old BALB/c mice were immunized with EPDPA015f or EPDPA015m in combination with aluminium adjuvant (50 μg/mouse) for three times with an interval of 10 d. The mice were sacrificed 10 d after the last immunization to collect blood and spleen samples. Serum antibody titers and cytokine levels were measured by ELISA, Luminex technique and enzyme-linked immunospot assay (ELISPOT). Mycobacterial growth inhibition assay (MGIA) was used to detect the ability of mouse splenocytes to inhibit the growth of Mtb in vitro. One-way analysis of variance and t-test were used for statistical analysis. Results:Both EPDPA015f and EPDPA015m could induce the production of various cytokines and IgG antibodies at a high level. The levels of cytokines related to Th1 (IL-2, TNF-α, IFN-γ), Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) as well as other proinflammatory cytokines (GM-CSF, IL-12) were higher in the EPDPA015f group than in the adjuvant group ( P<0.05). The titer of IgG antibody induced by EPDPA015f was as high as 1∶4×10 6. The results of MGIA showed that the numbers of Mtb (lgCFU) in the PBS, adjuvant, EPDPA015f and EPDPA015m groups were 3.46±0.11, 3.51±0.06, 2.98±0.09 and 3.19±0.08, respectively. The number of colonies in the EPDPA015f group was the least as compared with that in the other three groups ( P<0.001, P<0.001, P<0.01). Conclusions:The vaccine candidate EPDPA015f could elicit more comprehensive and high-level cellular and humoral immune responses, and exhibited superior in vitro inhibitory activity against the growth of Mtb. EPDPA015f had the potential to be used as a preventive vaccine or a booster vaccine

ObjectiveTo investigate the key compounds affecting the irritation and to clarify the effect of heating and the addition of ginger juice as the auxiliary material during the processing on the irritation of Magnoliae Officinalis Cortex（MOC） by comparing the irritation and composition of volatile oil in MOC and its different processed products. MethodVolatile oil in raw products， water-processed products， ginger-dried products， ginger-fried products（the amounts of ginger were 10%， 50%， respectively） of MOC were extracted by steam distillation and subjected to rabbit eye irritation experiment， and the volatile components of each sample were detected by gas chromatography-mass spectrometry（GC-MS）. Principal component analysis（PCA）and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to analyze the data of each sample by SIMCA 14.1. The relative contents of different processed products were compared two by two with those of and raw products or ginger-fried products， and the markers that might be related to the irritation were sorted out according to the principles of variable importance in the projection（VIP） value >1 and P<0.05， and the factors influencing the differences in irritation were analyzed. ResultCompared with the blank group， the administration groups all had irritation to the eyes of rabbits， and the degree of irritation was in the order of raw products>water-processed products>ginger-dried products>ginger-fried products（10%）>ginger-fried products（50%）. The results of PCA and OPLS-DA showed that there were differences in the volatile oil from raw products and different processed products. According to VIP value>1 and P<0.05， and combined with the results of eye irritation experiment， ten volatile compounds related to irritation changes were screened out. Among them， cis-cinnamaldehyde was only detected in raw products， the relative contents of β-caryophyllene， （+）-delta-cadinene， α-humulene， γ-muurolene， （-）-isoledene and citral all increased to different degrees， the contents of p-cymene， 1（10）-4-cadinadien-15-ol and β-eudesmol all decreased to different degrees. ConclusionThe irritation of MOC is reduced after heating and processing with ginger juice， and the synergistic effect of both is more effective for reducing irritation. Among the differential markers associated with changes in irritation， the increase in the relative content of citral is closely related to the addition of ginger juice， while the decrease in the relative contents of cis-cinnamaldehyde， p-cymene， 1（10）-4-cadinadien-15-ol is related to heating， and the changes of other components may be related to the synergistic effect of heating and ginger juice.

Objective:To investigate the role of indoxyl sulfate (IS) in myocardial hypertrophy and fibrosis through organic anion transporter-3 (OAT-3) and oxidative stress in H9C2 cells.Methods:Rat myocardial cells (H9C2) were cultured and divided into four groups: Control group, IS group, siRNA negative control group (siOAT-3), and siOAT-3+ IS group. The control group was cultured routinely without IS stimulation. The IS group was stimulated with 250 μmol IS. The siRNA negative control group was transfected with 20 nmol/L OAT-3 siRNA, and the siOAT-3+ IS group was transfected with OAT-3 siRNA 48 hours later, then stimulated with IS for 24 hours. Real-time polymerase chain reaction (RT-PCR) was used to detect and analyze the mRNA expression levels of OAT-3, NADPH oxidase-4 (Nox-4), antioxidant proteins [nuclear factor E2 related factor 2 (Nrf-2), heme oxygenase 1 (HO-1)], myocardial hypertrophy markers [atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), β-myosin heavy chain gene (β-MHC)], and fibrosis markers [transforming growth factor β1 (TGF-β1), Smad homologous protein 3 (Smad-3), collagen type Ⅰ (Collagen Ⅰ)] in each group. H9C2 cells were further divided into three groups: Control group, IS group, and N-acetylcysteine (NAC) group. The NAC group was pre-treated with the antioxidant NAC before stimulation with 250 μmol IS for 24 hours. RT-PCR was used to detect the mRNA expression levels of the above indicators.Results:The mRNA expression level of OAT-3 in the IS group was significantly higher than that in the control group, while the mRNA expression levels of OAT-3 in the siOAT-3 group and the siOAT-3+ IS group were significantly lower than those in the IS group (all P<0.001). Compared with the Control group, the mRNA relative expression levels of Nox-4, ANP, BNP, β-MHC, TGF-β1, Smad-3, and Collagen Ⅰ in H9C2 cells of the IS group were significantly increased (all P<0.001), while the mRNA expression levels of Nrf-2 and HO-1 were significantly decreased (all P<0.001). Compared with the IS group, the mRNA relative expression levels of Nox-4, ANP, BNP, β-MHC, TGF-β1, Smad-3, and Collagen Ⅰ in H9C2 cells of the siOAT-3 group and the siOAT-3+ IS group were significantly lower (all P<0.001), while the mRNA expression levels of Nrf-2 and HO-1 were significantly increased (all P<0.001). Pre-treatment with NAC significantly inhibited the high expression of Nox-4, ANP, BNP, β-MHC, TGF-β1, Smad-3, and Collagen Ⅰ mRNA induced by IS (all P<0.001), while significantly increasing the mRNA expression levels of Nrf-2 and HO-1 (all P<0.01). Conclusions:IS promotes myocardial hypertrophy and fibrotic factor overexpression in H9C2 cells through OAT-3 and oxidative stress.

Objective:To evaluate the immunogenicity and protective effect of a multicomponent recombinant protein vaccine EPRHP014 constructed independently and provide a scientific basis for developing new tuberculosis (TB) vaccine and effective prevention and control of TB.Methods:Three full-length Mycobacterium ( M.) tuberculosis protein antigens (EsxH, Rv2628, and HspX) and two epitope-predicted and optimized epitope-dominant protein antigens (nPPE18 and nPstS1) were selected, from which five protein antigens were used to construct a protein antigen composition EPRHP014, including a fusion expression multi-component protein antigen (EPRHP014f) and a multi-component mixed protein antigen (EPRHP014m) formed with the five single protein using clone, purification, and purification respectively. Multicomponent protein vaccines EPRHP014f and EPRHP014m were prepared with aluminum adjuvant, and the BCG vaccine was used as a control. ELISA detected the titer of serum-specific antibodies, the secretion of various cytokines was detected by ELISpot and Luminex, and immune protection was observed by the M.tuberculosis growth inhibition test in vitro. The results were statistically analyzed by t-test or rank sum test, and P<0.05 was considered a statistically significant difference. Results:Mice Immunized with EPRHP014m and EPRHP014f could produce highly effective IgG antibodies and their subtypes IgG1 and IgG2a, and the antibody titers were similar to those of mice immunized with BCG, with no statistical significance ( P>0.05). The number of spot-forming cells (SFC) secreting IFN-γ and IL-4 induced by EPRHP014f group was significantly higher than those by EPRHP014m group and BCG group ( P<0.05), but there was no significant difference in the number of SFC for IFN-γ and IL-4 induced between EPRHP014m group and BCG group ( P>0.05). The secretion levels of GM-CSF and IL-12p70 induced by the EPRHP014m group were higher than those of the BCG group ( P<0.05), but there was no significant difference in the levels of IL-6 and IL-10 induced between EPRHP014m group and BCG group ( P>0.05). There was no significant difference in the secretions of IL-6, IL-10, IL-12, and GM-CSF between the EPRHP014f and BCG groups ( P>0.05). EPRHP014m group, EPRHP014f group, and BCG group had obvious antibacterial effects in vitro, and the difference was insignificant ( P>0.05). Conclusion:Both EPRHP014f and EPRHP014m can induce strong humoral and cellular immune responses in mice after immunization, and have a strong ability to inhibit the growth of M. tuberculosis in vitro, indicating that the antigen composition EPRHP014 has good potential in the development and application of TB vaccine.

Nonpharmaceutical interventions (NPIs) have been commonly deployed to prevent and control the spread of the coronavirus disease 2019 (COVID-19), resulting in a worldwide decline in influenza prevalence. However, the influenza risk in China warrants cautious assessment. We conducted a cross-sectional, seroepidemiological study in Shandong Province, Northern China in mid-2021. Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains. A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic. The overall seroprevalence values against A/H1N1pdm09, A/H3N2, B/Victoria, and B/Yamagata were 17.8% (95% CI 16.2%-19.5%), 23.5% (95% CI 21.7%-25.4%), 7.6% (95% CI 6.6%-8.7%), and 15.0 (95% CI 13.5%-16.5%), respectively, in the study period. The overall vaccination rate was extremely low (2.6%). Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals (P < 0.001). Notably, the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic (P < 0.01). Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China.

Objective:To investigate the influencing factors of headache degree in migraine patients with patent foramen ovale (PFO).Methods:The clinical data of 124 migraine patients with PFO from January 2013 to June 2019 in Dalian Central Hospital Affiliated to Dalian Medical University were retrospectively analyzed. The right-to-left shunt of PFO was assessed by contrast-enhanced transcranial Doppler (c-TCD); the diameter of PFO, length of PFO tunnel and the presence of atrial septal aneurysm (ASA) were detected by transesophageal echocardiography (TEE); the degree of migraine was assessed by headache impact test-6 (HIT-6) scale. The relations between right-to-left shunt volume of PFO, diameter of PFO and degree of migraine were analyzed by Goodman-Kruskal γ test; the relations between the length of PFO tunnel, ASA and degree of migraine were analyzed by Spearman rank correlation analysis.Results:Among the 124 migraine patients with PFO, the c-TCD test result showed that small shunt volume was in 20 cases, medium shunt volume in 31 cases, and large shunt volume in 73 cases. The TEE test result showed that small foramen ovale in 76 cases, medium foramen ovale in 47 cases, and large foramen ovale in 1 case; long tunnel in 57 cases, and short tunnel in 67 cases; without ASA in 91 cases, and with ASA in 33 cases. The HIT-6 score result showed that some influence in 9 cases, significantly influence in 22 cases, and serious influence in 93 cases. The Goodman-Kruskal γ test result showed that right-to-left shunt volume of PFO and diameter of PFO were positive correlation with degree of migraine ( γ = 0.66, P<0.01; γ = 0.38, P<0.05). The Spearman rank correlation analysis result showed that ASA was positive correlation with degree of migraine ( r = 0.18, P<0.05), while the length of PFO tunnel was negative correlation with degree of migraine ( r = -0.23, P<0.05). Conclusions:The right to left shunt amount of PFO, diameter of PFO and the presence of ASA are positive correlation with degree of migraine, while the length of PFO tunnel is negative correlation with degree of migraine.

Objective:To investigate the influencing factors and regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective case-control study was conducted. The clinicopatho-logical data of 185 Siewert type Ⅱ and Ⅲ AEG patients in two medical centers (113 cases in Changzhi People's Hospital Affiliated to Changzhi Medical College and 72 cases in Heji Hospital Affiliated to Changzhi Medical College) from January 2017 to January 2022 were collected. There were 143 males and 42 females, aged (64±8)years. Patients underwent radical resection of AEG combined with inferior mediastinal lymph node dissection. Observation indicators: (1) clinicopathological charac-teristics of Siewert type Ⅱ and Ⅲ AEG patients; (2) analysis of influencing factors for inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG; (3) regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparsion between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. Results:(1) Clinicopathological characteristics of Siewert type Ⅱ and Ⅲ AEG patients. Pathologic staging as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ, degree of tumor invasion as stage T1, T2, T3 and T4, length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were found in 30, 61, 75, 7, 3, 41, 79, 50, 101, 46, 18, 8 cases of the Siewert type Ⅱ and Ⅲ AEG patients without inferior mediastinal lymph node metastasis, respectively, versus 0, 2, 10, 0, 0, 0, 5, 7, 4, 3, 2, 3 cases of the Siewert type Ⅱ and Ⅲ AEG patients with inferior mediastinal lymph node metastasis, showing a significant differences between them ( Z=?2.21, ?2.49, ?2.22, P<0.05). (2) Analysis of influencing factors for inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. Results of univariate analysis showed that pathological staging, depth of tumor invasion and length of esophageal invasion were related factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG ( odds ratio=2.48, 3.26, 2.03, 95% confidence intervals as 1.02?6.01, 1.21?8.80, 1.18?3.51, P<0.05). Results of multivariate analysis showed that depth of tumor invasion and length of esophageal invasion were independent influening factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG ( odds ratio=4.01, 2.26, 95% confidence interval as 1.35?11.96, 1.26?4.06, P<0.05). The inferior mediastinal lymph node metastasis probability of AEG patients with the length of esophageal invasion >3 cm and ≤4 cm was 9.47 times that of AEG patients with the length of esophageal invasion ≤1 cm. (3) Regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. The number of inferior mediastinal lymph nodes including No.110, No.111 and No.112 dissected in 185 patients of Siewert type Ⅱ and Ⅲ AEG were 127, 50 and 27. The number of lymph nodes dissected and the number of metastatic lymph nodes in No.110 and No.111 of patients with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 69, 4, 42, 4, 4, 1, 12, 4 and 23, 0, 17, 0, 7, 2, 3, 0, respectively. There were significant differences in metastatic lymph nodes in No.110 and No.111 of patients with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm ( χ2=8.45, 7.30, P<0.05). Of the 185 patients of Siewert type Ⅱ and Ⅲ AEG, the ratio of cases with inferior mediastinal lymph nodes metastasis was 6.49%(12/185). The ratio of inferior mediastinal lymph nodes metastasis in cases with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 3.81%(4/105), 6.12%(3/49), 10.00%(2/20), 27.27%(3/11), respectively. The ratio of No.110 lymph nodes metastasis in cases with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 2.86%(3/105), 6.12%(3/49), 5.00%(1/20), 27.27%(3/11), respectively, showing a significant difference among them ( χ2=8.26, P<0.05). Conclusions:Depth of tumor invasion and length of esophageal invasion are independent influening factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. The rate of inferior mediastinal lymph node metastasis increases with the increase of the length of esophageal invasion.