Objective To investigate the impact of donor kidney histopathological lesions on the risk of BK virus (BKV) infection and progression after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 326 kidney transplant recipients from deceased donors at the Department of Kidney Transplantation, the First Affiliated Hospital of Zhengzhou University, from January 2019 to June 2020. The recipients were divided into two groups based on whether BKV infection occurred after kidney transplantation: the BKV infection group (145 cases) and the non-BKV infection group (181 cases). The correlation between donor kidney histopathological findings from zero-hour biopsy and BKV infection, as well as the impact on the risk and progression of BKV infection, was analyzed. Results The incidence of BKV infection among the 326 kidney transplant recipients was 44.5% (145/326). The clearance rate of BKV after infection was 82.1% (119/145), while 17.9% (26/145) progressed to BKV viremia. Among the 326 qualified kidney biopsy specimens, 32 cases showed mild tubular atrophy, 324 cases had mild acute tubular injury, 27 cases exhibited mild hyaline arteriosclerosis, 10 cases had moderate to severe hyaline arteriosclerosis, 7 cases showed mild interstitial inflammation, 23 cases had mild interstitial fibrosis, 6 cases exhibited mild arterial intimal fibrosis, and 1 case had moderate to severe arterial intimal fibrosis. Multivariate logistic regression analysis revealed that male recipients, donor age and tubular atrophy were independent risk factors for BKV infection (all P<0.05). Tubular atrophy was also an independent risk factor for the progression from BKV uria to BKV viremia (P<0.05). Conclusions Donor kidney histopathological lesions have a certain impact on BKV infection and progression after kidney transplantation. Patients with more severe tubular atrophy in donor kidneys have a higher risk of BKV infection after kidney transplantation and are more likely to progress to BKV viremia.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

OBJECTIVE: To compare the registration accuracy of cone beam computed tomography (CBCT) images while registering to virtual craniodentofacial patients based on soft tissue and the dentition registration method. METHODS: Virtual dentofacial patients out of 13 selected participants who needed CBCT scanning were established by impression with a registered-block impression (RBI) based on digital dental images, three-dimensional (3D) facial images and maxillofacial CBCT images. CBCT images were processed in the Mimics software program, establishing the craniofacial virtual patients based on CBCT images (CCTs). Registration between virtual patients from RBI and CCT, using the soft tissue in lower half face (STE) and dentition (DTN) as the reference area, respectively, forming two kinds of virtual craniofacial patients based on digital dental images, 3D facial images and skeletal images of CBCT (hiding the soft tissue and dental casts from CBCT). Three-dimensional deviation analysis was performed in the upper half face and lower half face of facial images from CBCT between two kinds of virtual craniodentofacial patients and compared with 3D facial images from RBI and recorded as root mean square error (RMSE). Paired-t test was used to compare the deviations of RMSEs between the upper and lower half of the face and the upper half of the face of facial images from CCT, respectively, between the two kinds of virtual craniodentofacial patients based on STE and DTN methods. RESULTS: Paired-t tests showed that there was no statistically significant difference between the upper and lower half faces of facial images from CCT between STE and DTN (P>0.05), but the deviation of RMSEs of the upper half face of facial images from CCT in STE was smaller than those in DTN [(1.696±0.420) mm vs. (1.752±0.424) mm, P < 0.01]. CONCLUSION The registration accuracy of CBCT registered in virtual craniodentofacial patients using soft tissue as the reference area was higher.
Humans ; Cone-Beam Computed Tomography/methods* ; Imaging, Three-Dimensional/methods* ; Male ; Face/anatomy & histology* ; Female ; Adult ; Image Processing, Computer-Assisted/methods* ; Young Adult ; User-Computer Interface

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Objective To construct a curriculum system for higher vocational education in speech-language-hearing rehabilitation based on the World Health Organization rehabilitation competency framework(RCF),to align with international standards. Methods Based on RCF,curriculum theory and principles of vocational education psychology,a curriculum system and its content for higher vocational education in speech-language-hearing rehabilitation were developed.The curric-ulum content and core competencies were analyzed in detail across four levels:basic courses,specialized basic courses,specialized core courses and practical training courses. Results From the perspective of the seven competency domains of RCF,the theoretical and practical significance of con-structing a speech-language-hearing higher vocational education curriculum system based on RCF was systemati-cally elaborated.The study emphasized the importance of establishing competency-oriented higher vocational re-habilitation education for developing students'professional competence,adapting to job requirements,and pro-moting career development.A curriculum content system for speech-language-hearing rehabilitation higher voca-tional education based on RCF was systematically constructed,encompassing basic courses,professional cours-es,and practical training courses.The course names,main content and competency objectives at each level were analyzed in detail. Conclusion It is important to develop the course system of higher vocational education of speech-language-hearing reha-bilitation based on RCF.By comparing with international standards,the curriculum is optimized,focusing on im-proving students'vocational competence and promoting the international development.The curriculum system covers key areas such as core values,beliefs,practice and professionalism,integrates basic,core and practical training courses to achieve a competence-oriented curriculum system for higher vocational speech-language-hear-ing rehabilitation education.

Viral infection can induce endoplasmic reticulum stress(ERS)and unfolded protein re-sponse(UPR)in host cells,resulting in perturbation of endoplasmic reticulum homeostasis.To e-lucidate the action mechanism of isochlorogenic acid A(IAA)in regulating peste des petits rumi-nant virus(PPRV)-induced ERS and UPR,MTT assay,indirect immunofluorescence assay and Western blot were used to evaluate the anti-PPRV activity of IAA,and the effects of IAA on PPRV-induced ERS and PERK signaling pathway were studied by Western blot and quantitative real-time PCR.The results showed that the PPRV replication and virus-induced cytopathic in LDG-2 cells were significantly inhibited,and the survival rate of virus-infected cells was significantly in-creased due to IAA treatment.Compared with the virus control group,the expression levels of GRP78 and p-eIF2α,the ratios of p-PERK/PERK and p-eIF2α/eIF2α in IAA treated PPRV-infec-ted cells were significantly decreased.The expression level of GADD153 significantly decreased at 24,36 h,and significantly increased at 48,60 h.Furthermore,treatment with ERS inhibitor 4-PBA could significantly suppress the expression levels of GRP78,PPRV-N protein and GADD153 in PPRV-infected cells,and the ratios of p-eIF2α/eIF2α and p-PERK/PERK in PPRV-infected cells were also significantly decreased caused by treatment with IAA or 4-PBA and IAA combination.These findings implicated that the PPRV-induced ERS could be alleviated by inhibiting activation of the PERK-eIF2α-GADD1 53 signaling pathway,which led to restriction of PPRV replication in host cells.

Viral infection can induce endoplasmic reticulum stress(ERS)and unfolded protein reac-tion(UPR)in host cells.This study aims to further explore the effects of ERS induced by pest des petits ruminants virus(PPRV)infection on UPR signaling pathway,virus replication and apopto-sis of host cells.MTT assay,indirect immunofluorescence assay(IFA)and Western blot were used to observe the proliferation of PPRV in goat kidney cells(LDG-2).Western blot and real-time flu-orescence quantitative PCR(qRT-PCR)were used to observe the effects of PPRV infection on the expression levels of GRP78,PERK and its downstream signal molecules,apoptosis-related proteins Bcl-2 and Bax.The result indicated that the cell survival rate was significantly declined with evident cytopathic effect at 36 h post-infection,and the expression level of PPRV-N protein tended to be elevated,and was significantly higher than that of cell control at 30 h post-infection.Meanwhile,the expression levels of GRP78,p-eIF2α and GADD153,the ratio of p-PERK/PERK and p-eIF2α/eIF2α were significantly increased.Moreover,the expression levels of PPRV-N protein,GRP78,p-eIF2α and GADD1 53,the ratio of p-eIF2α/eIF2α and p-PERK/PERK were significantly decreased in PPRV-infected cells due to 4-PBA treatment.The expression level of apoptosis-related Bcl-2 was down-regulated,Bax was up-regulated,and the ratio of Bcl-2/Bax was significantly decreased.Therefore,the activation of PERK/eIF2α/GADD153 signaling pathway could be induced by PPRV infection resulting in alleviating of virus-induced ERS,which is beneficial to viral replication.Bloc-king PPRV-induced ERS could inhibit the activation of PERK signaling pathway and virus replica-tion.PPRV infection and prolonged ERS can induce apoptosis of LDG-2 cells.

MTT assay,indirect immunofluorescence assay(IFA)and real-time fluorescence quanti-tative PCR(qRT-PCR)were used to observe the proliferation of PPRV in goat kidney cells(LDG-2).Western blot and qRT-PCR were used to evaluate the effects of PPRV infection on the expres-sion levels of TLR2,MyD88,NF-κB signaling pathway-related factors and their downstream in-flammatory factors.The results indicated that the significantly decreased cell survival rate and ob-vious cytopathic effect were observed at 36 h post PPRV infection,and the mRNA expression level of PPRV-N gene was significantly up-regulated.At the same time,the expression levels of TLR2,MyD88,p-p65 and p-IκBα,the ratio of p-p65/p65 and p-IκBα/IκBα and the mRNA expression levels of downstream inflammatory factors TNFα,IL-1β,IL-4 and IL-10 were significantly increased.Mo-reover,the expression levels of PPRV-N mRNA,TLR2,MyD88,p-p65 and p-IκBα,the ratio of p-p65/p65 and p-IκBα/IκBα and the mRNA expression levels of downstream inflammatory factors IL-1β and IL-4 in PPRV-infected cells were significantly decreased in the presence of the inhibitor C29 of TLR2.These findings implied that the TLR2/MyD88/NF-κBα signaling pathway can be activated by PPRV infection,which is beneficial to the replication and spread of the virus.Blocking down the activation of TLR2 can inhibit MyD88/NF-κB signaling pathway and viral replication in PPRV-infected cells.

Objective To investigate the expression of TSR2 in gastric cancer and explore its correlation with progression of gastric cancer and the possible mechanism.Methods We retrospectively analyzed TSR2 expression in clinical specimens from 105 gastric cancer patients and the impact of TSR2 expression level on disease progression and 5-year postoperative survival of the patients.GO and KEGG enrichment analyses were used to predict the biological functions and mechanisms of TSR2.In gastric cancer MGC-803 cells with lentivirus-mediated TSR2 overexpression or knockdown,the changes in cell proliferation,invasion,and migration were assessed with CCK-8 and Transwell assays,and the expressions of p-PI3K and p-AKT were detected using Western blotting.Results TSR2 expression was significantly lower in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level,CA19-9 level,and T and N staging(P<0.05).A low TSR2 expression,CEA≥5 μg/L,CA19-9≥37 kU/L,T3-T4 stages,and N2-N3 staged were identified as independent risk factors affecting 5-year survival rate of the patients following radical surgery(P<0.05),and a high TSR2 expression was associated with a higher 5-year survival rate of the patients(P<0.001).Bioinformatics analysis suggested the functional involvement of TSR2 with the PI3K/AKT signaling pathway.MGC-803 cells overexpressing TSR2 showed significantly lowered proliferation,migration,and invasion capacities(P<0.05),while TSR2 knockdown produced the opposite effects(P<0.05).Western blotting showed that TSR2 overexpression reduced the phosphorylation of PI3K and AKT,and TSR2 knockdown caused the opposite changes in MGC-803 cells(P<0.05).Conclusion TSR2 is lowly expressed in gastric cancer tissues to adversely affect the patients'prognosis,and its overexpression inhibits gastric cancer cell proliferation,invasion,and migration possibly by downregulating the PI3K/AKT pathway.

Objective To investigate the mechanism underlying the neuroprotective effect of linarin(LIN)against microglia activation-mediated inflammation and neuronal apoptosis following spinal cord injury(SCI).Methods Fifty C57BL/6J mice(8-10 weeks old)were randomized to receive sham operation,SCI and linarin treatment at 12.5,25,and 50 mg/kg following SCI(n=10).Locomotor function recovery of the SCI mice was assessed using the Basso Mouse Scale,inclined plane test,and footprint analysis,and spinal cord tissue damage and myelination were evaluated using HE and LFB staining.Nissl staining,immunofluorescence assay and Western blotting were used to observe surviving anterior horn motor neurons in injured spinal cord tissue.In cultured BV2 cells,the effects of linarin against lipopolysaccharide(LPS)-induced microglia activation,inflammatory factor release and signaling pathway changes were assessed with immunofluorescence staining,Western blotting,RT-qPCR,and ELISA.In a BV2 and HT22 cell co-culture system,Western blotting was performed to examine the effect of linarin against HT22 cell apoptosis mediated by LPS-induced microglia activation.Results Linarin treatment significantly improved locomotor function(P<0.05),reduced spinal cord damage area,increased spinal cord myelination,and increased the number of motor neurons in the anterior horn of the SCI mice(P<0.05).In both SCI mice and cultured BV2 cells,linarin effectively inhibited glial cell activation and suppressed the release of iNOS,COX-2,TNF-α,IL-6,and IL-1β,resulting also in reduced neuronal apoptosis in SCI mice(P<0.05).Western blotting suggested that linarin-induced microglial activation inhibition was mediated by inhibition of the TLR4/NF-κB signaling pathway.In the cell co-culture experiments,linarin treatment significantly decreased inflammation-mediated apoptosis of HT22 cells(P<0.05).Conclusion The neuroprotective effect of linarin is medicated by inhibition of microglia activation via suppressing the TLR4/NF-κB signaling pathway,which mitigates neural inflammation and reduce neuronal apoptosis to enhance motor function of the SCI mice.