Aim: To explore the potential role of BK polyomavirus (BKV) in prostate tumorigenesis. Materials & methods: A total of 82 patients (no immunosuppression history) were divided into two groups. Group 1 included 32 patients receiving radical prostatectomy due to prostate adenocarcinoma. Group 2 consisted of 50 patients receiving transurethral resection of prostate or incision of prostate (TUIP) due to benign prostatic hyperplasia. Prostate tissue specimens of group 1 were obtained from two regions of the prostate: one was from the peripheral section of the prostate or proximal to the region where adenocarcinoma was confirmed by the preoperative needle biopsies (mark A region), the other was from the central section of the prostate or distal from the region where adenocarcinoma was confirmed by the needle biopsies (mark B region). If BKV alone was detected in either of the two regions, that case was regarded as BKV-positive prostate cancer. Those of group 2 were obtained from transrectal prostate biopsy before transurethral resection of prostate or transurethral incision of the prostate. Total DNA was extracted from each of the tissues and subjected to single or nested PCR using the β-globin system to detect targeted sequences within: the LTag gene; the VP1 gene and the transcriptional control region (TCR). Results: In group 1, BKV DNA sequences were detected in six cases (18.8%, 6/32), which were all in the A regions. Among the six cases, there were four cases with all of LTag, VP1 and TCR amplified, one case with LTag and TCR amplified, and one case with only the LTag amplified. In group 2, there was only one case (2.0%, 1/50) in which BKV DNA sequences were detected, and the only amplified fragment was VP1. The difference between the two groups was statistically significant (p = 0.008). Conclusion: BKV is often detected in the prostate cancer tissue and may be associated with progression of prostate cancer.
Abstract Introduction Previous evidence realized the critical role of histone in disease control. The anti‐inflammatory function of estradiol (E2) in sepsis has been documented. We here intended to unveil the role of extracellular histone H3 in sepsis regarding cell ferroptosis and the role of E2 in a such mechanism. Methods Clinical sample, cecal ligation and puncture (CLP)‐induced animal models and lipopolysaccharides (LPS)‐induced cell models were prepared for testing relative expression of extracellular histone H3 and E2 as well as analyzing the role of extracellular histone H3 and E2 in sepsis concerning cell viability, reactive oxygen species (ROS), and ferroptosis. Results Under sepsis, we found increased ferroptosis and extracellular histone H3 content, but reduced E2 concentration. Extracellular histone H3 facilitated ferroptosis of human umbilical vein endothelial cells (HUVECs) induced by LPS through activating the ROS/c‐Jun N‐terminal kinase (JNK) pathway. Moreover, E2 antagonized the effect of extracellular histone H3 on LPS‐induced HUVEC ferroptosis and sepsis injury in CLP‐induced animal models. Conclusion We highlighted that extracellular histone H3 facilitated lipopolysaccharides‐induced HUVEC ferroptosis via activating ROS/JNK pathway, and such an effect could be antagonized by E2.
Objective: To study prospectivelly the effect of postoperative rehabilitation following humeral head replacement (HHR), with tailor rehabilitation procedure.Method:20 patients with HHR who were admitted in our hospital from Mar.2002 to Feb.2003 were obtained.The rehabilitation process started as soon after surgery as the physician would allow, usually began at 24 hour postoperatively.Passive and active-assisted, active ROM exercises,daily strengthening and anti-resistance exercises were performed in different periods. Result:①All patients could perform most of daily living and passive ROM of shoulder were obtained nearly normal at 12 weeks postoperatively.②According the GEPI′s score of shoulder,it was from 23.1±1.5% at 8 weeks postoperatively to 8.3±1.6% at the end of rehabilitation.③All of the patients with HHR returned to work or obtained nearly normal function of the shoulder.Conclusion:Early rehabilitation can facilitate restoration function and range of motion for patients with HHR. The rehabilitation plan must be modified according to the patient′s condition and the state of the tissues observed during surgery. Author′s address Dept. of Physical Medicine and Rehabilitation, Beijing Jishuitan Hospital, Beijing,100035
Objective To study the preventive and remedial effects of ulinastatin(UST) on the acute pancreatitis with lung injury(APALI). Methods Retrospective analysis was performed on 205 patients,who were divided into two groups, control group and therapeutic group. One hundred and twelve patients in control group were treated with the conventional managements, while 93 patients in therapeutic group were treated with the conventional managements and UST. PaO2/FiO2, breathing frequency and X-ray of lung were analyzed to detect the difference of incidence of lung injury and curative effect on lung injury between both groups. Results The incidence of APALI was 35.6% in therapeutic group and 67.9% in control group. There was significant difference between both groups (P0.05). Compared with that in control group the degree of lung injury was lessened significantly in therapeutic group(P0.01). Conclusions UST can reduce the occurrence of APALI and improve APALI, and has significant preventive and remedial effects on APALI.
Despite the presence of neutrophil extracellular traps [NETs] in inflamed colon having been confirmed, the role of NETs, especially the circulating NETs, in the progression and thrombotic tendency of inflammatory bowel disease [IBD] remains elusive. We extended our previous study to prove that NETs constitute a central component in the progression and prothrombotic state of IBD.In all 48 consecutive patients with IBD were studied. Acute colitis was induced by the treatment of C57BL/6 mice with 3.5% dextran sulphate sodium [DSS] in drinking water for 6 days. Peripheral blood neutrophils and sera were collected from IBD patients and murine colitis models. Exposed phosphatidylserine [PS] was analysed with flow cytometry and confocal microscopy. Procoagulant activity was evaluated using clotting time, purified coagulation complex, and fibrin formation assays.We observed higher plasma NET levels and presence of NETs in colon tissue in patients with active IBD. More importantly, NETs were induced in mice with DSS colitis, and inhibition of NET release attenuated colitis as well as colitis-associated tumorigenesis. NET degradation through DNase administration decreased cytokine levels during DSS-induced colitis. In addition, DNase treatment also significantly attenuated the accelerated thrombus formation and platelet activation observed in DSS-induced colitis. NETs triggered PS-positive microparticle release and PS exposure on platelets and endothelial cells partially through TLR2 and TLR4, converting them to a procoagulant phenotype.NETs exacerbate colon tissue damage and drive thrombotic tendency during active IBD. Strategies directed against NET formation may offer a potential therapeutic approach for the treatment of IBD.
With the rapid advancement of artificial intelligence and communication technologies, connected autonomous vehicle (CAV) technology has made tremendous progress. However, due to the complexity of mixed traffic, CAV has not yet achieved scaled applications. Dedicated lanes for autonomous driving could provide a safer and more efficient driving environment for CAV, which would contribute to the realization of scaled applications for autonomous driving. Existing research extensively discusses the effectiveness of dedicated lanes, but most of these studies only consider the static spatial load attributes of roads, neglecting the importance of dynamic time scheduling optimization. To bridge this gap, this study firstly considers the interrelationship between ordinary lanes, traffic signals, and dedicated lanes comprehensively, and proposes a method for choosing deployment routes for autonomous driving dedicated lanes. Subsequently, based on the information provided by high definition maps (HDMaps), this research proposes a method for dynamically adjusting the usage rights of dedicated lanes for CAV. Finally, we conduct related comparative experiments to evaluate the impacts of the penetration rate of CAVs in mixed traffic, the occupancy rate in dedicated lanes, and the dynamic scheduling strategy on the overall efficiency of the traffic network.
Objective
To study the clinical features, diagnosis, treatment and genetic characteristics of granulomatosis disease (CGD) in neonates, and to improve the understanding of CGD.
Method
Clinical manifestations and treatments of one patient with CGD and in our hospital were analyzed. Key words including infant, newborn, chronic granulomatous lung and aspergillus infection were searched in Chinese medical databases, PubMed and Embase until 2018 September. The clinical features and genetic mutations of CGD reported in literature were summarized.
Result
The patient in our hospital was a full-term male infant naturally delivered with birth weight of 3 400 g. The onset of the disease was on the 19th day after birth, and the initial clinical manifestations included fever, cough, and then pulmonary abscess, diarrhea, recurrent skin infection, and infection. Anti-infection and symptom-alleviating treatments were not effective, and weight gain was poor. Laboratory examination indicated bacterial and fungal infection. The neutrophil respiratory burst test was positive and indicated CGD. Hetero-zygotic frameshift mutation [c.1599-1602delAGTT (p.V534Sfs*12)] of CYBB gene 13 exon was detected and the diagnosis of CGD was confirmed. The mother carried the heterozygous mutation and the father didn′t. Antifungal therapy was continued after the children got better and discharged from hospital. The patient was followed up until 3-month-old and his condition was stable. Our literature review revealed 28 reports including 108 cases of CGD infants, including 79 male cases (73.1%) and 21 female cases (19.4%). Most of the CGD infants (79/108, 73.1%) had the onset within 2 weeks of life. The main clinical features included pneumonia/pulmonary abscess/pleural effusion (87.0%), diarrhea (58.3%), perianal abscess (35.2%), skin (53.7%), (41.7%), and tuberculosis (26.9%). 75 cases had positive neutrophil respiratory burst test (69.4%), and 95 cases were diagnosed using genetic tests (88.0%). Over 300 loci of the CYBB gene mutation had been reported contributing to the disease. 28 cases had abnormal family history (25.9%), 19 cases received hematopoietic stem cell transplantation (17.6%), 41 cases had clinical improvement (38.0%), and 35 cases died (32.4%).
Conclusion
CGD is rare in neonatal period. The main clinical manifestations included recurrent with pathogens like aspergillus, tuberculosis and others. CGD can be diagnosed based on recurrent multiple bacterial or fungal infections, neutrophil respiratory burst test and gene tests. CGD should be considered among children with recurrent infections at early life stage, especial1y those with poor maternal history or positive family history.
Key words:
Granulomatous disease, chronic; Lung abscess; Aspergillus; Infant, newborn
Background: The generation of glycoprotein galactosyltransferase α 1, 3 (GGTA1) knockout pigs has greatly contributed to the reduction of hyperacute xenograft rejection. However, it is not clear whether porcine major histocompatibility complex antigen SLA can induce significant xenoantibody production in primate recipients after kidney xenotransplantation. Methods: We have performed six renal xenotransplants in rhesus monkeys using kidneys from GTKO/hCD55 pigs. The recipient monkeys received induction therapy with anti-thymocyte globulin (thymoglobulin) and anti-CD20mAb (rituximab) and maintenance therapy with tacrolimus, mycophenolate mofetil, and low-dose corticosteroids. Two of the six recipient monkeys (17R02 and 17R05) generated high levels of circulating antibodies against non-Gal antigens and developed acute humoral xenograft rejection on days 19 and 20. To investigate the presence of anti-SLA antibodies in xenograft rejection, we used serum samples collected before transplantation (day -7) and at the time of rejection (days 19 and 20) to measure IgM/IgG antibody binding against GTKO/hCD55 or GTKO/SLA-I/II KO pig PBMCs by flow cytometry. Results: The binding of IgM and IgG antibodies to GTKO/hCD55 pig PBMCs was significantly (5 to 10 times) higher in the serum of both monkeys at the time of rejection than in serum collected before transplantation (day -7), indicating that a large proportion of the antibody against non-Gal antigens was newly generated after transplantation. In the serums of both monkeys at the time of rejection, the levels of IgM and IgG binding decreased significantly after the additional deletion of SLA-I/II (IgM decreased by 45% and 83%, IgG decreased by 54.4% and 57.7%, respectively), suggesting that anti-SLA antibodies accounted for about half or more of the non-Gal-specific antibodies generated after transplantation. Conclusions: In conclusion, we demonstrate for the first time that porcine SLA antigen can induce higher levels of anti-SLA antibodies after xenotransplantation and may play important roles in GTKO pig-to-rhesus monkey xenotransplantation. It is suggested that knockout of the SLA antigen is necessary for pig-to-rhesus xenotransplantation. Major Scientific and Technological Project of Hainan province (ZDKJ2019009), China. References: 1. Fu R, Fang M, Xu K, et al. Generation of GGTA1-/-β2M-/-CIITA-/- Pigs Using CRISPR/Cas9 Technology to Alleviate Xenogeneic Immune Reactions. Transplantation. 2020;104(8):1566-1573. doi:10.1097/TP.0000000000003205 2. Ladowski JM, Hara H, Cooper DKC. The Role of SLAs in Xenotransplantation. Transplantation. 2021;105(2):300-307. doi:10.1097/TP.0000000000003303 3. Adams AB, Lovasik BP, Faber DA, et al. Anti-C5 Antibody Tesidolumab Reduces Early Antibody-mediated Rejection and Prolongs Survival in Renal Xenotransplantation. Ann Surg. 2021;274(3):473-480. doi:10.1097/SLA.0000000000004996 4. Fischer K, Rieblinger B, Hein R, et al. Viable pigs after simultaneous inactivation of porcine MHC class I and three xenoreactive antigen genes GGTA1, CMAH and B4GALNT2. Xenotransplantation. 2020;27(1):e12560. doi:10.1111/xen.12560 5. Byrne GW. Does human leukocyte antigens sensitization matter for xenotransplantation? Xenotransplantation. 2018;25(3):e12411. doi:10.1111/xen.12411 6. Hammer SE, Ho CS, Ando A, et al. Importance of the Major Histocompatibility Complex (Swine Leukocyte Antigen) in Swine Health and Biomedical Research. Annu Rev Anim Biosci. 2020;8:171-198. doi:10.1146/annurev-animal-020518-115014 7. Mulder A, Kardol MJ, Arn JS, et al. Human monoclonal HLA antibodies reveal interspecies crossreactive swine MHC class I epitopes relevant for xenotransplantation. Mol Immunol. 2010;47(4):809-815. doi:10.1016/j.molimm.2009.10.004 8. Martens GR, Ladowski JM, Estrada J, et al. HLA Class I-sensitized Renal Transplant Patients Have Antibody Binding to SLA Class I Epitopes. Transplantation. 2019;103(8):1620-1629. doi:10.1097/TP.0000000000002739 9. Ladowski J, Martens G, Estrada J, Tector M, Tector J. The desirable donor pig to eliminate all xenoreactive antigens. Xenotransplantation. 2019;26(4):e12504. doi:10.1111/xen.12504 10. Martens GR, Reyes LM, Li P, et al. Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs [published correction appears in Transplantation. 2018 Feb;102(2):e88]. Transplantation. 2017;101(4):e86-e92. doi:10.1097/TP.0000000000001646 11. Ladowski JM, Reyes LM, Martens GR, et al. Swine Leukocyte Antigen Class II Is a Xenoantigen. Transplantation. 2018;102(2):249-254. doi:10.1097/TP.0000000000001924 12. Ladowski JM, Martens GR, Reyes LM, et al. Examining the Biosynthesis and Xenoantigenicity of Class II Swine Leukocyte Antigen Proteins. J Immunol. 2018;200(8):2957-2964. doi:10.4049/jimmunol.1800022 13. Ladowski JM, Martens GR, Reyes LM, Hauptfeld-Dolejsek V, Tector M, Tector J. Examining epitope mutagenesis as a strategy to reduce and eliminate human antibody binding to class II swine leukocyte antigens. Immunogenetics. 2019;71(7):479-487. doi:10.1007/s00251-019-01123-y
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)