ObjectiveTo assess the efficacy of herpes virus entry mediator (HVEM) gene modifled dendritic cells (DCs) in protecting against myosin induced myocarditis,and to investigate the involving mechanism.MethodsWe treated experimental autoimmune myocarditis (EAM) mice with myosin-pulsed DCs which were transfected with HVEM-expressing adenovirus (Ad-HVEM) or control vectors,then evaluated myocarditis,plasm cTn [ and autoantibody by histopathology,fluoroimmunoassay,and ELISA,respectively.ResultsWe found that DCs transfected with Ad-HVEM (DC-Ad-HVEM) could protect against EAM.Further study showed DC-Ad-HVEM could produce regulatory cytokine IL-10,and IL-10 promoted the production of a key regulatory T cell subset which is important in peripheral tolerance.The T cells mediated protection against EAM.ConclusionThis study suggest that myosin-DC-Ad-HVEM cell gene therapy is a safe and effective way for inhibiting the development of EAM,and the signal net mediated by HVEM plays different roles in different cells.

Objective · To assess the morphological changes of mitral valve geometry after mitral valve repair by using real-time 3D transesophageal echocardiography. Methods · The clinical data including 3D echocardiography of 36 patients undergoing mitral valve repair for mitral valve prolapse and 56 patients without mitral valve diseases were collected. Parameters of mitral annular and leaflet geometry were acquired and analyzed. Results · The ellipse index of the two-dimensional view (E2D), and non-planar leaflet angle (θNPA) were decreased, while other parameters were increased significantly in patients with mitral valve prolapse compared with controls before mitral valve repair. After repair, patients displayed larger θNPA, and still smaller E2D.Some parameters also get smaller, such as the anterior to posterior diameter of the mitral annulus, the anterolateral to posteromedial coaptation diameter,the minimum circumference of the three-dimensional view of the annulus, the minimum area of the two-dimensional view of the annulus, the exposed area of the anterior leaflet, inter-commissural diameter. Other parameters were not changed significantly. All parameters showed no significant difference between respect group and resect group in posterior valve prolapse before and after mitral valve repair. Conclusion · The repair procedure can restore the function of the mitral valve effectively. In view of the morphology, the geometry of the mitral valve annulus is still different from the normal apparently after the mitral valve repair, but the normal morphology of the leaflets can be regained. It seems to have similar curative effect morphologically for patients with posterior leaflet prolapse to have respect or resect strategy.

Objective To assess the sequence variations in preS/S regions of occult hepatitis B virus (OHB) and their relationship to severe chronic hepatic injury. MethodsWe collected samples from HBsAg negative patients, and evaluated their HBV-DNA by nest-PCR. HBV-DNA positive samples were used for analysis of preS/S region by PCR sequencing. Results Sixty-nine cases with HBV-DNA were identified in 468 cases without HBsAg. The positive percents were 16％, 8.7％, 36.4％, 18.3％ and 0％in group of only HBcAb positive, only HBeAb positive, only HBeAg positive, both HBcAb and HBsAb positive and all indexes negative, respectively. The level of HBV-DNA of OHB was significant lower than that in HBsAg positive patients. Compared with HBsAg positive controls, preS/S deletion, M1I and Q2K in preS2 region, Q129N/R/P,G185R and S210R in S region were more common in OHB. Moreover, M1I and Q2K in preS2 region, G185R and S210R in S region in OHB with severe chronic hepatic injury were more common that those in OHB without severe chronic hepatic injury. Compared with HBsAg positive patients with severe chronic hepatic injury, the level of HBV-DNA was lower, while the frequency of M1I and Q2K mutation in preS2 region, G185R and S210R in S region were more common in OHB patients with severe chronic hepatic injury. ConclusionThe virological factors were different between OHB and HBsAg positive patients. The M1I and Q2K in preS2 region, G185R and S210R in S region might be useful for prognosis evaluation of OHB patients.

OBJECTIVETo clarify the role of midkine (MK) in vulvar carcinogenesis though examination of its expression in vulvar lesions including vulvar condyloma acuminata (VCA), vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell carcinomas (VSCC), and to analyze the relationship between MK expression and human papilloma virus (HPV) infection.

METHODSThirty VSCC, 15 VIN and 10 VCA patients were studied by streptavidin-biotin-immunoperoxidase method. MK expression was compared with clinicopathologic features of vulvar tumors.

RESULTSMK was expressed in 26 of 30 VSCC (87%), 3 of 5 VIN III and all VCA samples, whereas no MK expression was detected in the VIN I-II samples or in normal epithelium. The difference of MK expression between VIN III and VSCC was statistically significant (P < 0.05). MK was more intensely expressed in differentiated-type (well differentiated and moderately differentiated) VSCC than in undifferentiated-type (poorly differentiated) VSCC. There was no statistically significant correlation between MK expression and clinical stage, lymph node metastasis and HPV infection in VSCC. MK expression were observed in all HPV-positive specimens including 2 VSCC, 1 VIN III and all VCA.

CONCLUSIONSMK gene expression may be a late event in vulvar squamous cell malignant transformation, and may be associated with vulvar tumor cell differentiation. HPV-positive vulvar tumors expressed MK protein.

Carcinoma, Squamous Cell ; chemistry ; virology ; Carrier Proteins ; biosynthesis ; Condylomata Acuminata ; metabolism ; virology ; Cytokines ; Female ; Humans ; Papillomaviridae ; chemistry ; Papillomavirus Infections ; metabolism ; Precancerous Conditions ; chemistry ; virology ; Tumor Virus Infections ; metabolism ; Vulvar Diseases ; metabolism ; virology ; Vulvar Neoplasms ; chemistry ; virology

Objective:To investigate the efficacy and safety of daratumumab in the treatment of systemic light chain amyloidosis.Methods:The clinical data of 24 patients with systemic light chain amyloidosis who received daratumumab-based regimens in Sichuan Provincial People's Hospital from January 2020 to November 2022 were retrospectively analyzed. The treatment process of patients was summarized and the therapeutic efficacy was evaluated. Kaplan-Meier method was used to make survival analysis and the adverse reactions were analyzed.Results:All 24 patients included 2 cases (8.33%) of Mayo 2004 stageⅠ, 2 cases (8.33%) of Mayo 2004 stage Ⅱ and 20 cases (83.33%) of Mayo 2004 stage Ⅲ. All patients were treated with daratumumab-based regimen, and 17 patients had evaluable efficacy. In the chemotherapy regimens, 15 patients received DVd (daratumumab + bortezomib + dexamethasone) regimen, 7 patients received DVCd (daratumumab + bortezomib + cyclophosphamide + dexamethasone) regimen, 1 patient received DRd (daratumumab + lenalidomide + dexamethasone) regimen, and 1 patient received DTd (daratumumab +thalidomide + dexamethasone) regimen. After 1 course of daratumumab-based regimens in 17 cases with evaluable efficacy, the strict complete remission (sCR) rate was 41.18% (7/17), the overall response rate (ORR) was 88.24% (15/17). Among 17 patients who received daratumumab-based chemotherapy regimen as the first-line treatment, sCR rate of 11 cases with evaluable efficacy was 36.36% (4/11) after 1 course of treatment ORR was 90.90% (10/11). Among 5 relapsed/refractory patients, sCR rate of 4 cases with evaluable efficacy was 50.00% (2/4) after 1 course of treatment; ORR was 75.00% (3/4). Among 24 patients, renal involvement was found in 17 patients at the initial diagnosis. After 1 course of daratumumab-based chemotherapy regimen, ORR of 7 cases with evaluable efficacy was 85.71% (6/7), among which 42.86% (3/7) patients with renal involvement had an assessed renal response of very good partial remission (VGPR) or above. At the initial diagnosis, 19 cases had cardiac involvement; ORR of 14 cases with evaluable efficacy was 85.71% (12/14), among which 42.86% (6/14) patients had cardiac response to VGPR or above. After daratumumab-based chemotherapy regimen, the main adverse reactions were infusion-related adverse reactions, myelosuppression and infection, all of which were tolerated by the patients. The median follow-up time of 24 patients was 7.0 months (0.5- 16.5 months), the median progression-free survival time was 7.0 months (0.5-16.5 months) and the median overall survival time was 7.0 months (0.5-35.0 months).Conclusions:Daratumumab-based chemotherapy regimen has good efficacy and safety in the treatment of systemic light chain amyloidosis.