[The effect of glucose-6-phosphate dehydrogenase deficiency on allogeneic hematopoietic stem cell transplantation in patients with hematological disorders].

Objectives: To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients' complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) . Methods: 7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study. Results: The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia (n=3), acute lymphocytic leukemia (n=2), and severe aplastic anemia (n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6-64) d and 14 (7-70) d (P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively (P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively (P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively (P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively (P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively (P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively (P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively (P=0.387) . Conclusions: The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.

[Colorectal cancer with ß-catenin protein expression deficiency: a clinicopathological analysis].

Objective: To investigate the clinicopathological features and molecular characteristics of ß-catenin-deficient colorectal cancer. Methods: The clinical, pathological and molecular features of 11 colorectal cancers with ß-catenin protein loss diagnosed at the 960th Hospital of People's Liberation Army of China, from January 2012 to November 2022 were analyzed. Results: Among the 11 patients, 3 were males and 8 were females. Their age ranged from 43 to 74 years, with the median age of 59 years. Six were in the left colon and 5 were in the right colon. One of the 11 cases had lymph node metastasis, 10 cases were well and moderately differentiated adenocarcinoma, and 1 was mucinous adenocarcinoma. Eight cases were of TNM stage T4, 2 of T1 stage and 1 of Tis stage. ß-catenin protein was not detected using immunohistochemistry. Sanger sequencing revealed the presence of fragment-deletion mutation in exon 3 of CTNNB1 gene, resulting in loss of ß-catenin protein expression. Conclusion: ß-catenin deficiency is present in a small number of colorectal cancers and may be associated with exon 3 mutations of CTNNB1 gene.

[Clinical features and risk factors for invasive fungal sinusitis after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT. Methods: Nineteen patients with IFR after allo-HSCT at Peking University People's Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) . Results: Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10-59) years. The median IFR onset time was 68 (9-880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation (P=0.021) , hemorrhagic cystitis after transplantation (P=0.012) , delayed platelet engraftment (P=0.008) , and lower transplant mononuclear cell count (P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively (P<0.01) . Conclusion: Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

[Clinical significance of Epstein-Barr Virus detection in the cerebrospinal fluid of patients who underwent hematopoietic stem cell transplantation].

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.

[Clinical analysis of sirolimus as an alternative GVHD prophylaxis for patients with kidney injury undergoing allo-HSCT].

Objective: To explore the feasibility of sirolimus as an alternative graft versus host disease (GVHD) prophylaxis in patients with kidney injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective case series study. Medical records of 11 patients in Peking University People's Hospital from 1 August 2008 to 31 October 2022, who received sirolimus instead of cyclosporine to prevent GVHD, due to renal insufficiency after allo-HSCT, were analyzed retrospectively. Incidence of GVHD, infection, and transplant-associated thrombotic microangiopathy (TA-TMA), as well as renal function, were evaluated. Results: Among the 11 patients who received sirolimus, 6 were treated with haploidentical donor HSCT, and 5 were treated using matched sibling donor HSCT. The median (range) time of sirolimus administration was 30 (7-167) days after allo-HSCT, and the median (range) sirolimus course duration was 52 (9-120) days. During sirolimus treatment, 1 case did not undergo combined treatment with other prophylactic drugs, 3 cases received combined mycophenolate mofetil (MMF), and 1 case underwent combined CD25 monoclonal antibody treatment, while 6 cases had combined therapy with both MMF and CD25 monoclonal antibody. Of the 11 patients, 2 developed Grade Ⅲ acute GVHD, 1 developed severe pneumonia and died, and 1 developed TA-TMA, while nine patients had normal or improved renal function. Median (range) follow-up time was 130 (54-819) days. Non-relapse mortality was observed in 1 patient. Relapse mortality was also observed in 1 patient. Conclusion: Sirolimus-based alternative GVHD prophylaxis is a potentially viable option for patients undergoing allo-HSCT who cannot tolerate cyclosporine, but its efficacy and safety require further optimization and verification in prospective studies.

[Study on formulation of standard limits for trichloroethylene and tetrachloroethylene in "Standards for indoor air quality（GB/T 18883-2022）" in China].

There are clear indoor air pollution sources of trichloroethylene and tetrachloroethylene. A large number of epidemiological evidence has confirmed their carcinogenic toxicity and non-carcinogenic toxicity. Several countries and international organizations have paid attention to indoor air trichloroethylene and tetrachloroethylene. It has been also assessed that there should be certain potential health risk of indoor air trichloroethylene and tetrachloroethylene in China. Based on the latest research results of health risk assessment of indoor air trichloroethylene and tetrachloroethylene, the "Standards for indoor air quality (GB/T 18883-2022)" added trichloroethylene and tetrachloroethylene as indicators. The index limit of trichloroethylene is 6 µg/m3 for an 8-hour average concentration. The index limit of tetrachloroethylene is 120 µg/m3 for an 8-hour average concentration. The technical contents related to the determination of the standard limits of trichloroethylene and tetrachloroethylene in indoor air were analyzed and discussed, including the sources, the exposure, the health effects, the determination of the limit values, and the recommendations for standard implementation. It also proposed recommendations for the implementation of"Standards for indoor air quality (GB/T 18883-2022)".

Construction of molecular subgroups of ulcerative colitis.

OBJECTIVE: Ulcerative colitis (UC), a chronic inflammatory disease of the colon with unknown etiology, is characterized by remission and recurrence. At present, a considerable number of UC cases are misdiagnosed or delayed in diagnosis and treatment. We aimed to identify UC-related genes to aid the development of drugs for this condition. PATIENTS AND METHODS: Transcriptome data of 362 patients with UC and 126 control subjects were obtained from the Gene Expression Omnibus. The 362 patients with UC were subgrouped using unsupervised machine learning. R software was used to analyze the clinical characteristics of the subgroups, screen subgroup-specific genes, assess the relationships between gene modules and clinical characteristics using weighted gene co-expression network analysis, and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the subgroups. RESULTS: Patients with UC were classified into two subgroups. Genes specific to subgroup I included IL21R, ATP8B2, and PLEKHO1. Severe disease tended to be associated with immune cell infiltration; anti-tumor necrosis factor (TNF)-α antibodies and ustekinumab may have been effective in this subgroup. Subgroup II-specific genes included SLC4A4, EPB41L4B, and PLCE1. Patients in this subgroup had mild clinical conditions; however, their disease was more likely to progress to colorectal cancer. Thus, 5-aminosalicylic acid-based drugs may be effective for the treatment of UC in these patients. CONCLUSIONS: We divided UC into two molecular subgroups based on transcriptome data, providing molecular evidence for the development of diagnostic methods and individualized treatment strategies for UC.

[Safety and survival analysis of haplo-identical hematopoietic stem cell transplantation in patients with severe aplastic anemia who had previous failure to antithymoglobulin treatment].

Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [M (Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.

Development and validation of biomarkers related to PANoptosis in osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a high-incidence disease of the orthopedic system. However, studies on the molecular mechanisms of OA and pyroptosis, apoptosis, and necroptosis (PANoptosis) at the transcriptome level remain scarce. Therefore, this study purposed to detect biomarkers in OA and explore their relationship to the immune microenvironment. MATERIALS AND METHODS: OA-related expression data was sourced from the Gene Expression Omnibus (GEO) database. Subsequently, differentially expressed analysis and a Venn diagram were performed to obtain differentially expressed PANoptosis-related genes (DEPGs). Furthermore, the least absolute shrinkage and selection operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and random forest (RF) were implemented to screen diagnostic genes. Receiver operating characteristic (ROC) curves were performed to verify the diagnostic ability of the diagnostic genes. Next, immune infiltration analysis was performed to find the relationships between differential immune cells (OA vs. normal) and diagnostic genes. Finally, drug prediction analysis was also carried out, and the expression of diagnostic genes was verified in external datasets. RESULTS: A total of 62 DEPGs were identified, which were enriched for regulating apoptotic signaling pathways, tumor necrosis factor (TNF) signaling pathways, and other related pathways. Three feature genes, nuclear factor-kappa-B inhibitor-alpha (NFKBIA), RING finger protein 34 (RNF34), and serine incorporator 3 (SERINC3) were obtained by intersecting genes obtained by the LASSO regression algorithm, SVM algorithm, and RF algorithm and showed excellent diagnostic efficacy with the Area under the curve (AUC) values of individual genes were all greater than 0.7, indicating that the model was more effective. Immuno-infiltration analysis showed that RNF34 was positively correlated with CD56dim natural killer cells, type 17 helper T cells, and NFKBIA was positively correlated with plasmacytoid dendritic cells. Additionally, 12 drugs were predicted by NFKBIA, such as gambogic acid and dioscin. In addition, NFKBIA and SERINC3 were significantly downregulated, and RNF34 was upregulated in OA samples. CONCLUSIONS: Three genes (NFKBIA, RNF34, and SERINC3) related to PANoptosis, were obtained by bioinformatics analysis, which would provide a new direction for the diagnosis and treatment of OA.

Clinical efficacy of sclerotonyxis for acute angle-closure glaucoma with persistent high intraocular pressure.

OBJECTIVE: The aim of the study was to investigate the clinical effectiveness and safety of sclerotonyxis in acute angle-closure glaucoma (ACG) with persistent high intraocular pressure (IOP). PATIENTS AND METHODS: The clinical data of 50 eyes from 50 patients (mean age: 68.9±7.19 years) with acute ACG and persistently high IOP who were admitted to our department between January 2012 and January 2022 were retrospectively analyzed. Patients who were administered the maximum dose of systemic and topical anti-glaucoma drugs and still had an IOP of >40 mmHg 24 hours after admission underwent sclerotonyxis. After the IOP control, an individualized phase II treatment plan was designed according to the patient's ocular condition. RESULTS: Forty-eight patients showed improvement in their visual acuity 6 months postoperatively compared to their preoperative values. The mean IOPs were 54.84±7.82 mmHg and 21.34±7.81 mmHg 24 hours pre and postoperatively, respectively. The mean anterior chamber depth showed statistically significant differences pre and postoperatively (1.75±0.16 mm and 1.84±0.17 mm, respectively) (p<0.05). After IOP stabilized, four patients underwent YAG laser peripheral iridectomy, 18 underwent simple cataract phacoemulsification combined with intraocular lens (IOL) implantation, 21 underwent cataract phacoemulsification combined with IOL implantation and goniosynechialysis under a gonioscope, and 7 patients underwent combined surgery of glaucoma and cataract. The mean IOPs were 15.94±3.3 mmHg and 15.64±2.99 mmHg 1 week and 6 months after stage II surgery, respectively. Moreover, 42 eyes (84%) attained complete success and 8 eyes (16%) attained conditional success 6 months postoperatively. No serious complications, such as corneal endothelial decompensation, malignant glaucoma, vitreous or eruptive choroidal hemorrhage, and retinal detachment, were observed intraoperatively or postoperatively in both procedures. CONCLUSIONS: Sclerotonyxis can rapidly lower IOP, release the pupillary blockage, reconstruct the anterior chamber, and reduce systemic complications caused by long-term high-dose antiglaucoma drugs. Thus, it normalizes the IOP and provides a safe operating space for stage II surgery, effectively reducing complications in patients in a persistent high IOP state.

[Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation].

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

[Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation].

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

[Analysis and prediction of thyroid cancer morbidity and mortality trends in China].

Objective: To analyze the morbidity and mortality trends of thyroid cancer in China from 1990 to 2019, explore the causes of the trends, and predict morbidity and mortality in the future. Methods: The morbidity and mortality data of thyroid cancer in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease database. The Joinpoint regression model was used to describe the change trends. Based on the morbidity and mortality data from 2012 to 2019, a grey model GM (1,1) was constructed to predict the trends in the next ten years. The model was tested by the posterior error method and residual test method. Results: In all populations, men and women, the AAPC values of the crude morbidity rates were 4.15% (95%CI: 3.86%-4.44%, P<0.001), 5.98% (95%CI: 5.65%-6.31%, P<0.001) and 3.23% (95%CI: 2.94%-3.53%, P<0.001) respectively, the AAPC values of age-standardized morbidity rates were 2.47% (95%CI: 2.12%-2.83%, P<0.001), 3.98% (95%CI: 3.68%-4.29%, P<0.001), 1.65% (95%CI: 1.38%-1.93%, P<0.001), the AAPC values of crude mortality rates were 2.09% (95%CI: 1.92%-2.25%, P<0.001), 3.68% (95%CI: 3.45%-3.90%, P<0.001), 0.60% (95%CI: 0.50%-0.71%, P<0.001). The age-standardized mortality rates in men showed a fluctuating trend of first decrease (1990-1994), then increase (1994-2012), and then decrease (2012-2019) (AAPC=1.35%, 95%CI: 1.16%-1.53%, P<0.001). The age-standardized mortality rate in women continuously decreased (AAPC=-1.70%, 95%CI: -1.82%- -1.58%, P<0.001). The GM (1,1) models can be used for medium and long-term predictions. The results of the residual test show that the average relative error values of all models are less than 10.00%, the prediction accuracy values are more than 80.00%, and the prediction effects are good. The results of the posterior error method show that all the prediction results are good except the qualified prediction of the age-standardized morbidity rate in men. In 2029, the crude morbidity rates would increase to 3.57/100 000, 2.78/100 000, and 4.40/100 000, respectively, and the age-standardized incidence rates would increase to 2.38/100 000, 1.89/100 000, and 2.88/100 000, respectively, the crude mortality rates would increase to 0.57/100 000, 0.62/100 000 and 0.53/100 000, and the age-standardized mortality rates would decrease to 0.33/100 000, 0.42/100 000 and 0.27/100 000 in all population, men and women in China. Conclusions: The overall, gender- specific age-standardized mortality rates showed downward trends in the last decade or so, and the prediction results showed that it might further decline. However, the crude morbidity rates, age-standardized and crude mortality rates have been on the rise, and the population aging is becoming increasingly serious in China, which requires close attention and targeted prevention and control measures.

[Clinical value of nomogram model in evaluating the prognosis of cholangiocarcinoma after interventional therapy].

Objective: To investigate the clinical value and efficacy of the nomogram model in evaluating the prognosis of cholangiocarcinoma after interventional therapy. Methods: The clinical data of 259 patients with cholangiocarcinoma who received interventional therapy at the First Affiliated Hospital of zhengzhou University from January 2014 to June 2021 were retrospectively analyzed, including 148 males and 111 females, aged from 26 to 91 (65±12) years. They were randomly divided into a training group (181 cases) and a validation group (78 cases) in a ratio of 7∶3. Cox regression analysis was performed in the training group, independent risk factors affecting the prognosis of patients were screened, and a nomogram for 6-month, 1-year, and 2-year survival was constructed. The performance of the nomogram was analyzed by calculating the area under the receiver operating characteristic curve (AUC) value, calibration curve, and decision curve, and the predictive efficacy of the model was evaluated in the validation group. Results: There was no significant difference in baseline data between the training group and the validation group, which was comparable. Regression analysis showed that T stage (T2: HR=0.147,95%CI: 0.077-0.281;T3: HR=0.207,95%CI: 0.122-0.351;T4: HR=0.864,95%CI: 0.537-1.393), tumor diameter (17-33 mm: HR=0.201,95%CI: 0.119-0.341;≥33 mm: HR=0.795,95%CI: 0.521-1.211) and differentiation degree(middle differentiation: HR=3.318,95%CI: 2.082-5.289;highly differentiation: HR=1.842,95%CI: 1.184-2.867) were risk factors affecting the prognosis of interventional therapy for cholangiocarcinoma. The AUC values of the survival curve prediction models were generally consistent between the training and validation groups, and the AUC values of the training group at 6 months, 1 year, and 2 years were 0.925 (95%CI: 0.888-0.963), 0.921 (95%CI: 0.877-0.964) and 0.974 (95%CI: 0.957-0.993), respectively. In the validation group, the 6-month, 1-year, and 2-year AUC values were 0.951 (95%CI: 0.911-0.991), 0.917 (95%CI: 0.857-0.977) and 0.848 (95%CI: 0.737-0.959), respectively, and the AUC values were all greater than 0.8, suggesting that the nomogram had better discrimination ability. The calibration curves of the prediction models of the two groups were basically consistent, and the shape of the calibration curves at 6 months and 1 year fitted the ideal curve, while the fitting degree of the calibration curves at 2 years was relatively poor. The decision curve showed the high clinical utility of this nomogram in predicting the 6-month, 1-year survival of patients with cholangiocarcinoma. Conclusions: T stage, tumor diameter, and differentiation are independent risk factors affecting the prognosis of patients with interventional cholangiocarcinoma, and the nomogram model proposed in this study has good distinguishing ability and exact clinical value for prognosis evaluation.

[Correlation between contrast-enhanced ultrasound parameters and Crohn's disease activity].

Objective: By investigating the correlation between quantitative parameters of contrast enhanced ultrasound (CEUS) and commonly used activity assessment indicators of Crohn's disease (CD), and comparing the predictive power of laboratory inflammatory indicators with CEUS on Crohn's disease (CD), the significance of CEUS was evaluated. Methods: A case-control study. From October 2019 to December 2021, the clinical data of 67 patients with CD who were diagnosed by endoscopy and underwent contrast-enhanced ultrasonography were retrospectively analyzed in the First Affiliated Hospital with Nanjing Medical University, and their routine ultrasound and CEUS parameters, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn's disease activity index (CDAI) and simplified endoscopic score for Crohn's disease (SES-CD) were collected. Using SES-CD as the standard, the patients were divided into a remission group and an active group, and the correlation of laboratory inflammatory indexes and contrast-enhanced ultrasound parameters with CDAI and SES-CD were evaluated. Besides, the ROC curve was used to analyze the predictive efficacy of each index on CD endoscopic activity. Results: A total of 67 patients were included in this study. According to the SES-CD score, there were 17 patients in the remission group and 50 patients in the active group. Except for the coefficient of the enhancement wash in slope and time to peak (TTP), the peak intensity (PI), area under the angiography curve, and laboratory inflammatory indexes were significantly different between the two groups (P<0.05), which also showed a moderate positive correlation with CDAI and SES-CD (P<0.05). ROC analysis showed that among the non-invasive indicators, PI and area under the angiography curve had the highest AUCs for predicting CD endoscopic activity, which were 0.912 and 0.891, respectively; with SES-CD taking >3 as the cut-off value, the corresponding sensitivities were 78.0% and 72.0%, with specificities of 100.0% and 94.1%, respectively. Conclusion: CEUS can objectively and repeatedly evaluate the disease activity of CD patients, and has great clinical application value, which can be used as a reliable imaging method for diagnosis and follow-up of patients with Crohn's disease.

[Clinical efficacy of a modified no-touch technique in the establishment of autologous arteriovenous fistula].

Objective: To explore the clinical efficacy of a modified no-touch technique (MNTT) in establishing autogenous arteriovenous fistulas (AVF) in hemodialysis patients. Methods: A total of 63 patients with AVF which was first established by MNTT in the Department of Nephrology, Suzhou Science and Technology Town Hospital from January 2021 to August 2022 were retrospectively included. The clinical data, ultrasound evaluation data of AVF, AVF maturity rate and AVF patency rate were collected. Subsequently, the AVF rate of patients in the MNTT group was compared with the patency rate of patients in the conventional operation group in the same hospital from January 2019 to December 2020. The Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the difference in postoperative patency rate between the two groups. Results: There were 63 cases in the MNTT group, with 39 males and 24 females, and aged (60±17) years. Meanwhile, there were 40 cases in the conventional operation group, including 23 males and 17 females, and aged (60±13) years. In the MNTT group, the immediate patency rate was 100% (63/63) after surgery, and the AVF maturation rate at 2, 4 and 8 weeks postoperatively were 54.0% (34/63), 85.7% (54/63), and 90.5% (57/63), respectively. The primary patency rate was 90.0% (45/50), 85.0% (34/40), 82.9% (29/35), and 81.0% (17/21) at 3, 6, 9 months, and 1 year after the operation, respectively, and the assisted patency rates were all 100.0%. The one-year primary patency rate in the MNTT group was higher than that in the conventional surgery group (81.0% versus 63.5%, log-rank χ2=5.12, P=0.023). Ultrasound results showed that in the MNTT group, AVF veins were evenly dilated, the vascular wall gradually thickened, the brachial artery blood flow gradually increased, and spiral laminar flow occurred in the cephalic vein and radial artery. Conclusion: AVF established by MNTT features with fast maturity and a high patency rate, which is worthy of clinical promotion.

Long noncoding RNA ITGB1 promotes migration and invasion of clear cell renal cell carcinoma by downregulating Mcl-1.

The article "Long noncoding RNA ITGB1 promotes migration and invasion of clear cell renal cell carcinoma by downregulating Mcl-1", by X.-L. Zheng, Y.-Y. Zhang, W.-G. Lv, published in Eur Rev Med Pharmacol Sci 2019; 23 (5): 1996-2002-DOI: 10.26355/eurrev_201903_17238-PMID: 30915742 has been retracted by the author for the following reasons: After the publication of this article, the authors reviewed the process of the experiment and found there were mistakes in the study setting. Authors state that the cancer tissues of 60 inpatients collected in the article included cancer tissues and adjacent tissues. However, the registration and storage of the experiment were not careful, and the cancer tissues were confused with the adjacent tissues. For this reason, the results of this article are not accurate and complete. After consultation among the authors, in line with the rigorous attitude towards scientific research, authors agreed that it was necessary to withdraw the article and make further research and improvement. *After publication, the article was also questioned on PubPeer. Concerns were raised about Figures and in particular Figure 3 which shows overlapping images. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17238.

[Interventional treatment and early-stage follow-up of pulmonary atresia with intact ventricular septum].

Objective: To explore the application value of percutaneous peripheral interventional therapy in pulmonary atresia with intact ventricular septal (PA-IVS). Methods: Retrospective case summary. The data was collected from 25 children who were hospitalized at the Children's Hospital,Zhejiang University School of Medicine from August 2019 to August 2022, had been diagnosed with PA-IVS by echocardiography, and underwent interventional treatment. The sex, age, weight, operation time, radiation exposure time, and radiation dose of the patients were collected. The patients were divided into the arterial duct stenting group and the non-stenting group. Preoperative tricuspid annular diameters and Z scores, right ventricular length diameters, and right ventricular/left ventricular length-diameter ratios were compared by paired t-tests. Right ventricular systolic pressure difference, oxygen saturation, lactic acid before and after the surgery were compared for 24 children who received percutaneous balloon pulmonary valvuloplasty. Right ventricular improvement in 25 children after operation was analyzed. The correlation between postoperative oxygen saturation and postoperative right ventricular systolic blood pressure difference, the degree of pulmonary valve opening and the Z value of tricuspid valve ring in the non-stenting group were analyzed. Results: A total of 25 patients with PA-IVS were enrolled in the study, of whom 19 were males and 6 females, with an age at surgery of 12 (6, 28) days and a weight of (3.7±0.5) kg. One of them underwent only stenting of the arterial duct; 20 children underwent only percutaneous pulmonary valve perforation and balloon angioplasty; 4 children underwent both procedures. The Z-value of the tricuspid ring was -1.5±1.2 in the group with arterial duct stenting, and -0.1±0.4 in the group without stenting (t=2.77, P=0.010). The tricuspid regurgitant flow rate 1 month after surgery was significantly lower than the preoperative ((3.4±0.6) vs. (4.8±0.9) m/s, t=6.62,P<0.001). In the 24 children with percutaneous pulmonary valve perforation and balloon angioplasty, the preoperative right ventricular systolic blood pressure was (110±32) mmHg, and the postoperative systolic blood pressure was (52±19) mmHg (1 mmHg=0.133 kPa) (F=59.55, P<0.001). The factors that may affect postoperative oxygen saturation in 20 cases of non-stenting group were analyzed. The results suggested that the pre and post-operative right ventricular systolic blood pressure differences (r=-0.11, P=0.649), and the pulmonary valve orifice opening (r=-0.31, P=0.201) and tricuspid annulus Z value (r=-0.18, P=0.452) at 1 month after the operation were not significantly correlated with the postoperative oxygen saturation. Conclusions: Interventional therapy can be used as the first choice for one-stage operation of PA-IVS. Percutaneous pulmonary valve perforation and balloon angioplasty are more suitable for children with well-developed right ventricles, tricuspid annulus, and pulmonary arteries. While the smaller the tricuspid annulus, the more dependent it is on the ductus arteriosus and thus patients are more suitable for arterial duct stenting.