To investigate the relationship of the variation of virulence and the external capsid proteins of the pandemic duck hepatitis A virus type 1(DHAV-1) isolates,the virulence,cross neutralization assays and the complete sequence of the virion protein 1(VP1) gene of nine virulent DHAV-1 strains,which were isolated from infected ducklings with clinical symptoms in Shandong province of China in 2007-2008,were tested.The fifth generation duck embryo allantoic liquids of the 9 isolates were tested on 12-day-old duck embryos and on 7-day-old ducklings for the median embryonal lethal doses(ELD50s) and the median lethal doses(LD50s),respectively.The results showed that the ELD5s of embryonic duck eggs of the 9 DHAV-1 isolates were between 1.9 × 106/mL to 1.44 × 107/mL,while the LD50s were 2.39 × 105/mL to 6.15 × 106/mL.Cross-neutralization tests revealed that the 9 DHAV-1 isolates were completely neutralized by the standard serum and the hyperimmune sera against the 9 DHAV-1 isolates,respectively.Compared with other virulent,moderate virulent,attenuated vaccine and mild strains,the VP1 genes of the 9 strains shared 89.8％-99.7％ similarity at the nucleotide level and 92.4％-99.6％ at amino acid level with other DHAV-1 strains.There were three hypervariable regions at the C-terminus(as 158-160,180-193 and 205-219) and other variable points in VPI protein,but which didn't cause virulence of DHAV-1 change.

Objective To investigate the relationships and types between pulmonary subsolid nodules and bronchi and vessels,and their diagnostic values in differentiating subsolid nodules.Methods MSCT images of 40 subsolid nodules were retrospectively reviewed.The relationships between subsolid nodules and bronchi were divided into five types.Type Ⅰ:the bronchi were “cutoff”in the solid part of nodules.Type Ⅱ:the bronchi were distortion and extension in the solid parts of nodules.Type Ⅲ:the bronchi were distortion and extension in the GGO parts of nodules.Type Ⅳ:the bronchi were normal course in the GGO parts of nodules.Type Ⅴ:the bronchi were circumvent nodule lesions.The relationships between subsolid nodules and vessels were categorized into four types.Type Ⅰ:vessels passing by SSNs;Type Ⅱ:intact vessels passing through SSNs;Type Ⅲ:distorted,dilated or tortuous vessels seen within SSNs;Type Ⅳ:more complicated vessels other than described above.The relationship types were correlated to pathologic and/or clinical findings of subsolid nodules.Results Of 40 subsolid nodules,4 were preinvasive nodules,6 micro infiltrating adeocarcinomas and 30 invasive ones that were pathologically proven.Types Ⅰ,Ⅱ,Ⅲ and Ⅳ vascular relationships were observed in 0,8,21 and 11 subsolid nodules,respectively.Type Ⅲ relationship was the dominating one.All 11 subsolid nodules were invasive adenocarcinomas,when the relationship between subsolid nodules and vessle was type Ⅳ.There were 17 invasive adenocarcinomas,2 preinvasive ones,and 2 infiltrating ones when the relationship between subsolid nodules and vessel was type Ⅲ.Correlation analysis showed strong correlation between invasive adenocarcinoma and type Ⅲ and Ⅳ relationships.There was significantly statistical significance among 3 groups of relationships between subsolid nodule and vessels(χ2 =1 5.1 90,P =0.004).Types Ⅰ,Ⅱ,Ⅲ,Ⅳ and V brochi relationships were observed in 20,5,6,9 and 0 subsolid nodules,respectively.Type I relationship was the dominating relationship.There were 1 7 invasive adenocarcinomas, 1 preinvasive one,2 micro invasive ones when the relationship between subsolid nodules and bronchi were typeⅠ.There was significantly statistical significance among 3 groups of relationships between subsolid nodule and bronchi (χ2 =23.81 1,P =0.001 ).Conclusion Different subsolid nodules have different relationships with bronchi and vessels.Understanding and recognizing the characteristic subsolid nodule-bronchi and subsolid nodule-vessel relationships may help to identify which nodules are more likely to be malignant.

Objective:To determine the expression of T follicular helper (Tfh) cell-related molecules inducible costimulator (ICOS) and programmed cell death-1 receptor (PD-1) in skin lesions of patients with bullous pemphigoid (BP), and to explore the role of Tfh cells in the pathogenesis of BP.Methods:Twenty-one paraffin-embedded tissue specimens were collected from 21 patients with confirmed BP in Dalian Dermatosis Hospital from 2014 to 2017, including 7 females and 14 males with an average age of 72.57 years. Ten normal skin tissue specimens served as control group. Immunohistochemical SP method was used to determine the expression of ICOS and PD-1 in BP skin lesions and normal skin tissues.Results:In BP lesions, ICOS and PD-1 were mainly expressed in the basal layer, spinous layer, granular layer and stratum corneum, especially in the spinous layer in the epidermis, and also expressed in inflammatory cells in the dermis. Additionally, they were both expressed in the cytoplasm and nuclei, occasionally expressed on the cell membrane. However, ICOS and PD-1 were rarely expressed in the normal skin tissues. The expression rates of ICOS and PD-1 were significantly higher in the BP group (85.71% [18/21], 47.62% [10/21], respectively) than in the normal control group (both were 0; P < 0.001, < 0.05, respectively) .Conclusion:Tfh cell-related molecules ICOS and PD-1 may play important roles in the pathogenesis of BP.

AIM:To investigate the inhibitory effect of the"decoction for soothing liver and removing stasis and toxicity(SGQYJDF)"on hepatocellular carcinoma(HCC)proliferation in nude mice by inducing ferroptosis via the tumor protein 53(p53)/solute carrier family 7 member 11(SLC7A11/xCT)/glutathione peroxidase 4(GPX4)pathway.METHODS:An ectopic subcutaneous tumor model was established by injecting SK-Hep-1 cells subcutaneously into the right axilla of nude mice.Upon formation of tumor,the mice were randomly divided into five groups(i.e.,control group,low-,medium-and high-dose SGQYJDF groups and medium-dose SGQYJDF plus Sorafenib group).Each group of mice was orally administered with the corresponding therapy for 14 consecutive days,during which the tumor size was observed regularly.At the end of treatment,the tumor growth inhibition rate was calculated based on tumor mass,and histopatho-logical changes were observed by HE staining.Then,the levels of malondialdehyde(MDA),glutathione(GSH)and fer-rous ions(Fe2+)were detected by colorimetric assays.The expression of the proliferation markers Ki-67 and GPX4 was de-tected by immunohistochemistry(IHC).The expression of p53 and xCT was detected by Immunofluorescence(IF).And the expression of p53,xCT and GPX4 was determined by Western blot.RESULTS:(1)SGQYJDF was found to dose-de-pendently decrease tumor volume(P＜0.01)and inhibit tumor mass growth(P＜0.01),and meanwhile,reduce the per-centage of Ki-67-positive cells(P＜0.01)and their proliferation ability in tumor tissues,as compared to the control group.(2)In terms of Ferroptosis-related indicators,SGQYJDF was found to dose-dependently increase the levels of Fe2+ and MDA but decrease the level of GSH in tumor tissues(P＜0.01),as compared to the control group.(3)In terms of protein expression,SGQYJDF was found to dose-dependently upregulate the expression of p53(P＜0.05)but inhibit the expres-sion of xCT(P＜0.05)and GPX4(P＜0.01).Notably,medium-dose SGQYJDF plus sorafenib showed a stronger effect than high-dose SGQYJDF.CONCLUSION:Our findings suggest that SGQYJDF can induce Ferroptosis to inhibit the proliferation of subcutaneously transplanted tumor tissues in nude mice by upregulating the expression of p53,and inhibit-ing the expression of xCT and GPX4.

Objective:To investigate the effect of fluid resuscitation and circulatory support, directed by different target mean arterial pressure (MAP), on abdominal blood flow, gastrointestinal function and inflammatory response in septic shock patients with hypertension.Methods:A prospective randomized controlled study was conducted. Hypertensive patients with septic shock admitted to the department of intensive care unit (ICU) of Liuzhou People's Hospital from January 1, 2019 to May 31, 2020 were enrolled. Patients were randomly divided into the low MAP groups (low standard group, LS group) or high MAP group (high standard group, HS group). According to the Surviving Sepsis Campaign Guidelines in 2016 and the updated guideline in 2018, all patients were given treatment of primary disease, fluid resuscitation, supportive management. The target MAP was 65-70 mmHg (1 mmHg = 0.133 kPa) in LS group, and was 75-80 mmHg in HS group. Acute gastrointestinal function injury (AGI) classification was performed on the 1st, 3rd and 7th day. The mean flow rate (Vm) and resistance index (RI) of superior mesenteric artery were evaluated using ultrasound, and the gastrointestinal function was dynamically evaluated using the modified single section ultrasonic gastric antrum method. The gastric antrum movement index (MI) and gastric empaging time (GET) were recorded. The levels of inflammatory markers in serum were detected by enzyme linked immunosorbent assay (ELISA), such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), procalcitonin (PCT) and vascular endothelial growth factor (VEGF). The target MAP, the days of use of vasopressors and the amount of fluid resuscitation were recorded.Results:A total of 208 hypertensive patients with septic shock were enrolled, including 109 in the LS group and 99 in the HS group. There were no significant differences in gender, age, acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score between the two groups when diagnosed. After treatment, there was no significant difference in AGI classification between the LS group and HS group on the 1st day. On the 3rd and 7th day, there were statistical differences between the two groups (3rd day: proportion of Ⅰ, Ⅱ, Ⅲ, Ⅳ grades were 25.69%, 56.88%, 11.93%, 5.50% in LS group, 15.15%, 54.55%, 25.25%, 5.05% in HS group, respectively, χ 2 = 7.900, P = 0.048; 7rd day: proportion of Ⅰ, Ⅱ, Ⅲ, Ⅳ grades were 44.96%, 49.54%, 3.67%, 1.83% in LS group, 31.31%, 52.53%, 11.11%, 5.05% in HS group, respectively, χ 2 = 8.178, P = 0.042). The Vm of superior mesenteric artery was higher and the RI was lower in the LS group than those in the HS group on day 1, 3 and 7 [Vm (cm/s): 21.72±3.02 vs. 19.50±2.83, 20.42±2.62 vs. 17.02±1.99, 26.52±2.70 vs. 22.47±4.03; RI: 0.86±0.05 vs. 0.92±0.04, 0.87±0.05 vs. 0.95±0.05, 0.81±0.03 vs. 0.85±0.03, all P < 0.01]. The MI was higher and the GET was shorter in the LS group than those in the HS group on day 3 and day 7 [MI: 3.00±0.33 vs. 2.60±0.29, 4.50±0.51 vs. 3.90±0.33; GET (minutes): 86.01±19.78 vs. 100.99±25.01, 71.00±16.37 vs. 84.98±20.18, all P < 0.01]. In addition, the levels of serum TNF-α, IL-6, PCT, VEGF were lower in the LS group than those in the HS group after 3 days of treatment [TNF-α (ng/L): 147.05±28.32 vs. 256.99±27.04, IL-6 (ng/L): 762.99±57.83 vs. 1 112.30±118.32, PCT (μg/L): 37.00±5.58 vs. 56.00±12.36, VEGF (ng/L): 123.00±19.78 vs. 167.01±21.55, all P < 0.05]. The target MAP was maintained at (68.02±4.71) mmHg in LS group, and (79.04±3.04) mmHg in HS group. The difference between the two groups was statistically significant ( P < 0.01). Compared with the HS group, the days of using vasopressors was shorter in LS group (days: 3.50±1.27 vs. 4.55±1.47), and the amountof fluid was reduced significantly (mL: 1 602.29±275.49 vs. 2 000.30±272.59, both P < 0.01). Conclusion:Maintaining a low target mean arterial pressure (65-70 mmHg) in hypertensive patients with septic shock can improve blood supply of superior mesenteric artery, protect the gastrointestinal function, reduce the level of inflammatory factors, and diminish the duration of using vasopressors and the amount of fluid.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*