Objective:To investigate the expression of protein kinase D2(PRKD2)in bladder cancer(BLCA)tissue using bioinformatics analysis method and its effect on the prognosis of BLCA patients,and to clarify the role of PRKD2 in the occurrence and development of BLCA.Methods:The data from 9 normal bladder samples,19 BLCA paracancerous samples,and 407 BLCA tumor samples were downloaded from the UCSC Cancer Genome Database.The Mann-Whitney U test was applied to analyze the difference in expression of PRKD2 mRNA in BLCA tumor and normal bladder tissues,and the Human Protein Atlas(HPA)database was used for proteomic validation.DESeq2 package in R software was applied to screen the differentially expressed genes(DEGs)in BLCA tissue in PRKD2 low-and high-expression groups.The co-expression heatmaps of PRKD2 were plotted using the ggplot2 package,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation analysis and pathway enrichment analysis of DEGs,and Gene Set Enrichment Analysis(GSEA)was used to obtain the gene sets that were significantly enriched for DEGs.The BLCA samples were divided into low-and high-expression groups according to the expression level of PRKD2,and the correlations between PRKD2 expression and immune cell infiltration in the BLCA patients were analyzed with GSVA package.The relationship between PRKD2 and prognosis of BLCA patients was further analyzed using the survival package and the survminer package.The PRKD2 gene mutations in BLCA tissue were analyzed using the cBioPortal database.The cystitis,bladder polyp and BLCA tissues were collected,and the expression levels of interleukin-17F(IL-17F)protein in BLCA and control tissues were detected using immunohistochemical staining technique.Results:PRKD2 was highly expressed in a variety of malignant tumors,and the expression levels of PRKD2 mRNA and protein in BLCA tissue were significantly increased compared with those in normal bladder tissue(P＜0.05).Single gene differential analysis of PRKD2 yielded a total of 1 058 DEGs,of which a total of 29 genes were up-regulated and 1 029 were down-regulated.The results of GO functional enrichment analysis showed that DEGs were mainly enriched in the biological process(BP),such as chemical stimuli involved in sensory perception,Cajal body,and endopeptidase inhibitor activity.The results of KEGG pathway analysis showed that DEGs were mainly enriched in the pathway of Staphylococcus aureus infection and the pathway of maturity onset diabetes of the young.GSEA analysis showed that DEGs were mainly enriched in the Notch signaling pathway,the retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ)-like receptor signaling pathway,the cytoplasmic DNA screening pathway,the base excision repair signaling pathway,natural killer(NK)cell-mediated cytotoxicity signaling pathway and T cell receptor signaling pathway.The results of immune infiltration analysis indicated that the expression of PRKD2 was positively correlated with five types of cells,such as activated dendritic cells(aDC),NK CD56dim cells and central memory T cells(Tcm)(P＜0.05),and negatively correlated with three types of immune cells,including macrophages,effector memory T cells(Tem)and plasmacytoid dendritic cells(pDC)(P＜0.05).The clinical characteristic subgroup analysis results showed that the expression levels of PRKD2 mRNA in BLCA patients who were over 70 years old and developed lymphovascular invasion were decreased(P＜0.05);the overall survival(OS),disease-specific survival(DSS)and progression-free interval(PFI)in the BLCA patients with PRKD2 high expression were significantly longer than those with PRKD2 low expression(P＜0.05).The univariate and multivariate Cox analyses indicated that distant metastasis,primary therapy outcome and clinicopathologic stage were the important factors affecting BLCA prognosis.About 9％patients had PRKD2 gene mutations,including missense mutation,gene amplification,mRNA low or high expression,and multi-motif mutation.The immunohistochemistry results showed that the expression level of IL-17F protein in BLCA tissue was significantly higher than that in cystitis tissue(P＜0.05).Conclusion:The expression level of PRKD2 in BLCA tissue is obviously increased,which could up-regulate the expression of IL-17F protein,and the decrease of PRKD2 protein expression may be a potential factor for the poor prognosis of BLCA patients.

Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

Objective:To explore the safety and efficacy of TBF conditioning regimen of thiotepa, fludarabine and busulfan in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for recipients with hematological malignancies unsuitable for BUCY conditioning regimen (busulfan, cyclophosphamide & mBUCY).Method:A retrospective analysis was conducted for 20 recipients with malignant hematologic diseases receiving TBF conditioning regimen before haplo-HSCT at Soochow Hopes Hematologic Hospital from January 2020 to December 2023. The regimen-related toxicity of TBF was assessed by the Bearman scoring criteria. For comparing the safety and efficacy of TBF conditioning regimen with mBUCY regimen, propensity score matching was performed in a ratio of 1: 2 with disease type, patient age and gender as matching factors.Result:Mild oral mucositis and gastrointestinal reaction were major side-effects without severe cardiac events. Median time to neutrophil and platelet engraftments in TBF group was 11 and 18 days with comparable engraftment in mBUCY group. TBF regimen had a significantly lower incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) than mBUCY at Day 100 (5% vs 35%, P=0.01). No significant inter-group difference existed in overall survival (68% vs 62%, P=0.98) while 1-year incidence of graft-versus-host disease-free, relapse-free survival (GRFS) improved (63% vs 37%, P=0.06) in TBF group. Conclusion:TBF is a promising conditioning regimen with low toxicity and decent safety for haplo-HSCT. TBF patients tend to have a lower incidence of grade Ⅱ-ⅣaGVHD and better GRFS than mBUCY.

To explore the efficacy and safety of immunoadsorption (IA) in removing de novo donor specific antibody (DSA) after allogeneic hematopoietic stem cell transplantation (HSCT), the relevant clinical data were retrospectively reviewed for one female patient of severe aplastic anemia (SAA). Desensitization treatment with IA after HSCT was offered for removing de novo DSA and ultimately promoting platelet engraftment at First Affiliated Hospital of Soochow University in March 2021.

【Objective】 To investigate the clinical characteristics and diagnosis and treatment of passenger lymphocyte syndrome (PLS) in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). 【Methods】 A total of 489 patients who underwent allo-HSCT in Suzhou Hongci Hematology Hospital were retrospectively enrolled. The clinical process, diagnosis and treatment measures and prognosis of four patients complicated with PLS after transplantation were analyzed. 【Results】 Among the 489 patients, 4 were diagnosed with PLS. The blood types of donor/recipient ABO were all secondary incompatible (The blood type of donors were O and the recipients were A or B). The overall incidence of PLS in allo-HSCT was 0.82%(4/489)and 2.2%(4/179)in transplants with donor/recipient secondary incompatible ABO-blood types. PLS occured in 6-13 days after donor stem cell infusion. Clinical manifestations were dizziness and fatigue, low back pain, jaundice, deepening urine, rapid decrease in hemoglobin on laboratory tests, elevated indirect bilirubin and lactate dehydrogenase, positive urobilinogen, positive direct anti-human globulin test (DAT), and anti-A or anti-B antibodies against recipient red blood cells were detected in plasma. After the treatment of O-type washed red blood cells, methylprednisolone, gamma globulin, rituximab and other treatments, the hemolysis was improved. All patients achieved engraftment of neutrophil and platelet. Red blood cell transfusion was halted in 3 weeks. 【Conclusion】 PLS is a rare complication of allo-HSCT, which mainly occurs in allo-HSCT patients with secondary incompatibility of ABO blood group of donor/recipient. The clinical prognosis is good after properly treatment.

【Objective】 To investigate the correlation between early immune reconstitution and clinical outcomes in patients with acute lymphoblastic leukemia (ALL) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). 【Methods】 The basic information and treatment data of 99 patients with ALL undering allo-HSCT from December 2018 to February 2022 were collected. The proportions of CD3⁺ T, CD3⁺CD4⁺ T, CD3⁺CD8⁺ T and CD3^-CD16⁺CD56⁺ NK cells were detected before and 30, 60 and 90 days after transplantation using flow cytometry. The correlation between early cellular immune reconstitution and neutrophil engraftment, platelet engraftment, infection, and acute and chronic graft-versus-host disease (GVHD) was analyzed. 【Results】 Among 99 ALL patients, the median time of neutrophil engraftment was day +11 (range, 8-28), and the median time of platelet engraftment was day +14 (range, 10-120). The cumulative incidence of blood stream infection (BSI) was 11.10% and the cumulative incidence of CMV within 100 days of transplantation was 40.40%. The cumulative incidence of EBV within 100 days was 7.10%. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 22.30%. The cumulative incidence of chronic graft-versus-host disease (cGVHD) within 1 year of transplantation was 16.20%. 1 -year cumulative relapse rate was 13.84%. The 1 -year cumulative disease-free survival (DFS) for all patients was 80.60% and the 1-year overall survival (OS) was 90.30%. The CD4⁺/CD8⁺ ratio was positively associated with the development of aGVHD at 30 days post-transplant (OR 1.21, 95CI 1.01-1.45, P<0.05). The proportion of CD16⁺ CD56⁺ NK cell were higher in the group without BSI than that in the BSI group before and 30 days after transplantation (P < 0.05). The proportion of CD4⁺ T-cell were lower in the CMV infection group than that in the group without CMV infection at 60 and 90 days post-transplant(P<0.05). The higher level of CD4⁺ T-cells at 60 days post-transplant was a protective factor for CMV infection within 100 days (HR 0.91, 95CI 0.84-0.99, P<0.05). 【Conclusion】 Early immune reconstitution after allo-HSCT in patients with ALL is associated with aGVHD, CMV and BSI.

Objective:To explore the efficacy of tislelizumab combined with umbilical cord blood transplantation (UCBT) in relapsed/refractory acute myeloid leukemia (R/R AML) patients.Methods:The diagnosis and treatment of 1 patient with R/R AML who received tislelizumab bridging to UCBT after the failure of re-induction treatment in the First Affiliated Hospital of Soochow University in November 2021 was retrospectively analyzed.Results:The 59-year-old male patient with R/R AML achieved a complete remission after initial induction chemotherapy regimen of decitabine and venetoclax, and then additional consolidation therapy regimens of decitabine and middle-dose cytarabine, middle-dose cytarabine and idarubicin were performed. The patient relapsed 16 months later and failed to achieve a second remission after re-induction therapy regimens of cladribine, azacitidine, venetoclax combined with chemotherapy, and homoharringtonine, cytarabine combined with granulocyte colony-stimulating factor. Tislelizumab significantly reduced tumor burden and the patient achieved the complete remission after bridging to UCBT. After transplantation, the patient was given maintenance treatment with azacitidine and he had sustained remission without severe transplant-related complications during 9-month follow-up.Conclusions:The use of tislelizumab bridging UCBT can be a potential therapeutic strategy for R/R AML patients.

Objective:To evaluate the functional and anatomical outcomes of autologous single retinal pigment epithelium (RPE) transplantation for severe obsolete submacular hemorrhage (SMH) in late age-related macular degeneration (AMD).Methods:A retrospective clinical study. From January 2012 to December 2015, 11 patients with AMD (11 eyes) with obsolete SMH who were diagnosed and treated by pars plana vitrectomy (PPV) combined with autologous RPE transplantation at the Department of Ophthalmology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were included. Among them, there were 9 eyes in 9 males and 2 eyes in 2 females. All the eyes underwent the examinations of best corrected visual acuity (BCVA) and optical coherence tomography; 4 eyes underwent macular fixation function (MAIA) at the same time. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. All eyes were treated with PPV combined with autologous single-layer RPE transplantation or autologous RPE-choroidal full-thickness transplantation, and were divided into S group and C group, with 5 and 6 eyes respectively. The differences of age ( t=-0.363), gender composition ratio ( χ2=0.549), course and thickness of SMH ( t=0.118, 0.231), average times of anti-vascular endothelial growth factor drug treatments ( t=0.129), times of PPV ( t=-0.452) between the two groups were not statistically significant ( P>0.05). The follow-up period was 6-40 months after the operation, and the BCVA, MAIA, graft status and complications of the eyes after the operation were observed. The comparison of continuous variables between groups was performed by independent-sample t test; the comparison of categorical variables was performed by χ2 test. Results:At the last follow-up, the average logMAR BCVA of the eyes in group S and C were 1.62±0.34 and 1.03±0.20, respectively; group C was better than group S, however, the difference was not statistically significant ( t=1.532, P=0.160). There were 4 eyes (80%, 4/5) and 6 eyes (100%, 6/6) in S group and C group with BCVA better than preoperative, the difference was no statistical significance ( χ2=0.677, P=0.895). There were 2 (40%, 2/5) and 3 (50%, 3/6) eyes with logMAR BCVA better than 1.0 in S group and C group, and the difference was not statistically significant ( χ2=0.572, P=0.423). After the operation, 6 eyes of grafts were in good condition and 5 eyes were in poor condition; the BCVA of grafts in good condition was significantly higher than that of poor condition, the difference was statistically significant ( t=4.894, P=0.001). Among the 4 eyes that underwent MAIA examination, 2 eyes were unstable and diffusely fixed on the graft; the fixation point was located at the normal retina adjacent to the graft area in 2 eyes. Secondary subretinal hemorrhage occurred in 3 eyes after the operation; the intraocular pressure was high in 1 eye after the operation. During the follow-up period, no intraocular infection, secondary retinal detachment, recurrent choroidal neovascularization or low intraocular pressure occurred in all eyes. Conclusions:Both autologous single-layer RPE transplantation and autologous RPE-choroidal full-thickness transplantation can help stabilize or even improve the visual function of eyes with severe SMH secondary to advanced AMD. The visual acuity after surgery is closely related to the state of the graft.

Objective To analyze the radiological features of idiopathic pediatric meningiomas and explore their relationships with pathological grading,misdiagnoses,and blood loss during surgery.Methods We retrospectively reviewed 29 cases of pathologically confirmed pediatric meningiomas with pre-operative magnetic resonance imaging in Beijing Tiantan Hospital from November 2014 to July 2018.We assessed the imaging features to explore their relationships with pathological grading,misdiagnoses,and blood loss during surgery. Results Among the 29 cases,7 intraparenchymal meningiomas,5 extraparenchymal meningiomas,4 ventricular meningiomas,and 1 transcranial meningioma were misdiagnosed.Tumor location was significantly associated with possibility of misdiagnoses(
Child ; Humans ; Magnetic Resonance Imaging ; Meningeal Neoplasms/diagnostic imaging* ; Meningioma/diagnostic imaging* ; Retrospective Studies

Objective To evaluate the effect of ropivacaine-induced convulsion on hippocampal synaptic development in neonatal rats.Methods Sixty 21-day-old Sprague-Dawley neonatal rats,weighing 40-41 g,were randomly divided into 3 groups (n=20 each) using a random number table:control group (group C),single convulsion group (group SC),and recurrent convulsion group (group RC).Normal saline 0.1 ml was intraperitoneally injected in group C.Group SC received single intraperitoneal injection of 0.5％ ropivacaine 33.8 mg/kg.In group RC,0.5％ ropivacaine 33.8 mg/kg was intraperitoneally injected once a day for 5 consecutive days.The rats developed convulsion were included in the study.Five rats were selected at 24 h,3 days and 7 days after convulsion and at the age of 60 days in C and SC groups,and at 24 h,3 days and 7 days after the last convulsion and at the age of 60 days in group RC,the rats were sacrificed,and the hippocampus was removed for examination of the ultrastructure of neurons (with a electron microscope) and for determination of the number of synapses,synaptic space and thickness of synaptic density.Results Compared with group C,the number of synapses was significantly decreased,and the synaptic space was widened at 24 h and 3 days after convulsion,and the thickness of synaptic density was thinned at 24 h after convulsion in group SC,and the number of synapses was significantly decreased,and the synaptic space was widened,and the thickness of synaptic density was thinned at 24 h,3 days and 7 days after convulsion in group RC (P＜0.05).Compared with group SC,the number of synapses was significantly decreased,the synaptic space was widened,and the thickness of synaptic density was thinned at 24 h,3 days and 7 days after convulsion in group RC (P＜0.05).There was no significant difference in the parameters mentioned above at the age of 60 days between the three groups (P＞0.05).Neurons exhibited nuclear swelling,mitochondria showed edema,and disrupted mitochondrial cristae and vacuoles were observed at 24 h and 3 days after convulsion,and these changes mentioned above were significantly attenuated at 24 h,3 days and 7 days after convulsion.Conclusion Ropivacaine-induced convulsion exerts no effects on hippocampal synaptic development in neonatal rats.