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Xu-Wen Fu,1,&ast; Yan Bi,2,&ast; Jia-Lu Wei,3 Min Qi,3 Long Zhu,3 Ying Pu,3 Jing-Liang Liu,2 Xiang Li,3 Xin-Hua Cun4 1Department of Pharmacy, Kunming Third People’s Hospital/Yunnan Clinical Medical Center for Infectious Diseases, Kunming, 650041, People’s Republic of China; 2Department of Radiology, The People’s Hospital of Lincang, Lincang, 677000, People’s Republic of China; 3Department of Radiology, Kunming Third People’s Hospital/Yunnan Clinical Medical Center for Infectious Diseases, Kunming, Yunnan, 650200,People’s Republic of China; 4Department of Orthopaedics, Kunming Third People’s Hospital/Yunnan Clinical Medical Center for Infectious Diseases, Kunming, 650041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Li, Department of Radiology, Kunming Third People’s Hospital/Yunnan Clinical Medical Center for Infectious Diseases, Kunming, Yunnan, 650041, People’s Republic of China, Tel +86 18108857532, Email li_xiang115@126.com Xin-Hua Cun, Department of Orthopaedics, Kunming Third People’s Hospital/Yunnan Clinical Medical Center for Infectious Diseases, Kunming, Yunnan, 650041, People’s Republic of China, Email xinhuacun_cun6@21cn.comObjective: To observe the clinical characteristics of fungal and Brucella infections of the lumbar spine and explore the key points for their differential diagnosis.Methods: The clinical data of 12 patients with fungal infection (the fungal group) and 31 patients with Brucella infection (the Brucella group) of the lumbar spine confirmed by microbiological culture and antigen test were retrospectively analysed. The differences in the clinical characteristics and imaging manifestations were observed between the two groups.Results: The peripheral blood neutrophil ratio, erythrocyte sedimentation rate, serum total protein and serum globulin levels in the fungal group were higher compared with the Brucella group, while the peripheral blood lymphocyte count, lymphocyte ratio and albumin-globulin ratio were lower in the fungal group compared with the Brucella group (P < 0.05). As for imaging examinations, the proportion of bone destruction centred on the intervertebral disc with surrounding osteosclerosis on computed tomography (CT) imaging showed a statistical difference between the Brucella group and the fungal group (P < 0.05). Fungal infection patients showed more osteosclerosis-free areas around the bone destruction on magnetic resonance imaging (MRI) than Brucella infection patients.Conclusion: There are certain similarities in clinical manifestations between fungal and Brucella infections of the lumbar spine, but the haematological indices and image features of CT and MRI can effectively differentiate between them, providing guidance for the clinical differential diagnosis.Keywords: mycosis, brucellosis, imaging, differential diagnosis

Objective: The clinical significance of incidentally detected pancreatic duct (PD) dilatation at ultrasound (US) without a visualized underlying cause is unclear. We aimed to assess the role of subsequent MRI (including MRCP) and to identify US imaging and laboratory findings predictive of underlying pancreaticobiliary malignancy at the time of initial US., Materials and Methods: Patients with incidentally detected PD dilatation at ultrasound from 2011 to 2019 that had an ensuing MRI were included. Based on MRI results patients were divided into three groups: malignant pancreaticobiliary causes, benign causes and idiopathic PD dilatation. Subsequently the diagnostic ability of MRI was assessed. Initial ultrasound findings and laboratory results were compared between groups to identify predictors of underlying pancreaticobiliary pathology. A p-value < .05 was considered statistically significant., Results: In 37/59 (63%) patients PD dilatation was confirmed on MRI. MRI demonstrated malignant 7/59 (12%) and benign 10/59 (17%) causes of PD dilatation detected at initial ultrasound. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy of MRI to ascertain the cause of PD dilatation was 89%, 100%, 95%, 100% and 97% respectively. Patients with a larger magnitude of PD dilatation, concomitant CBD dilatation and elevated lipase values were more likely to have underlying pancreaticobiliary malignancy (p < 0.05). No patient with initial negative MRI had pancreaticobiliary malignancy on subsequent work-up., Conclusion: Incidentally detected PD dilatation on ultrasound is an important finding and should prompt referral to MRI. MRI is an accurate, noninvasive method for identifying the underlying cause of PD dilatation in these patients and in excluding pancreaticobiliary malignancy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: This study aimed to determine the expression pattern of autoantibody proteins from the serum of grade IV glioblastoma patients. Materials & methods: We performed high throughput antibody profiling via the Sengenics i-Ome ® Protein Array to determine the differentially expressed autoantibodies. Results: The results portrayed that anti-COL4A3BP and anti-HSP90AA1 were among the upregulated autoantibodies in glioblastoma sera. Conclusion: The selected autoantibodies offer promising targets for future glioblastoma pathogenesis. However, further validation is required to elucidate the autoantibody signature in glioblastoma patients.

Pancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy. Analyzing circulating extracellular vesicles (cEVs) using 'liquid biopsies' offers an attractive approach to diagnose and monitor disease status. However, it is important to differentiate EV-associated proteins enriched in patients with pancreatic ductal adenocarcinoma (PDAC) from those with benign pancreatic diseases such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). To meet this need, we combined the novel EVtrap method for highly efficient isolation of EVs from plasma and conducted proteomics analysis of samples from 124 individuals, including patients with PDAC, benign pancreatic diseases and controls. On average, 912 EV proteins were identified per 100µL of plasma. EVs containing high levels of PDCD6IP, SERPINA12 and RUVBL2 were associated with PDAC compared to the benign diseases in both discovery and validation cohorts. EVs with PSMB4, RUVBL2 and ANKAR were associated with metastasis, and those with CRP, RALB and CD55 correlated with poor clinical prognosis. Finally, we validated a 7-EV protein PDAC signature against a background of benign pancreatic diseases that yielded an 89% prediction accuracy for the diagnosis of PDAC. To our knowledge, our study represents the largest proteomics profiling of circulating EVs ever conducted in pancreatic cancer and provides a valuable open-source atlas to the scientific community with a comprehensive catalogue of novel cEVs that may assist in the development of biomarkers and improve the outcomes of patients with PDAC.

Objective: The aim of this study was to investigate the role of the Hounsfield unit value of chest CT non-contrast enhanced scan in evaluating the severity of anemia in HIV-infected patients., Methods: Patients with HIV infection combined with anemia admitted to the Kunming Third People's Hospital were retrospectively collected and divided into mild anemia, moderate anemia, and severe anemia groups by peripheral hemoglobin (HB) content and calculated the ratio of ventricular septum density (VSD) to left ventricular density (LVD) and VSD to right ventricular density (RVD); then, the above patients were divided into the critical value group and the non-critical value group according to HB and compared the differences of LVD, RVD, VSD/LVD, and VSD/RVD in the two groups of patients., Results: A total of 126 patients were included, with a mean age of 47.9 ± 11.1 years; 43 cases were in the mild anemia group, 59 cases were in the moderate anemia group, and 24 cases were in the severe anemia group; the differences in LVD, RVD, VSD/LVD, and VSD/RVD were significant in the three groups; VSD/LVD was an independent predictor for the diagnosis of anemia critical value in the non-critical value group vs critical value group by multifactorial binary logistic regression analysis, and the ROC was plotted using VSD/LVD with an area under the curve of 0.731., Conclusions: The measurement of cardiac cavity density and ventricular septal density under CT plain film scan has a high accuracy in evaluating the severity of anemia in patients with HIV infection and can quickly determine the severity of HIV infection in the early stage and treat it as soon as possible., Competing Interests: Conflict of interest: The authors of this study declared no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Objective: In this study, we examined the value of chest CT signs combined with peripheral blood eosinophil percentage in differentiating between pulmonary paragonimiasis and tuberculous pleurisy in children., Methods: Patients with pulmonary paragonimiasis and tuberculous pleurisy were retrospectively enrolled from January 2019 to April 2023 at the Kunming Third People's Hospital and Lincang People's Hospital. There were 69 patients with pulmonary paragonimiasis (paragonimiasis group) and 89 patients with tuberculous pleurisy (tuberculosis group). Clinical symptoms, chest CT imaging findings, and laboratory test results were analyzed. Using binary logistic regression, an imaging model of CT signs and a combined model of CT signs and eosinophils were developed to calculate and compare the differential diagnostic performance of the two models., Results: CT signs were used to establish the imaging model, and the receiver operating characteristic (ROC) curve was plotted. The area under the curve (AUC) was 0.856 (95% CI: 0.799-0.913), the sensitivity was 66.7%, and the specificity was 88.9%. The combined model was established using the CT signs and eosinophil percentage, and the ROC was plotted. The AUC curve was 0.950 (95% CI: 0.919-0.980), the sensitivity was 89.9%, and the specificity was 90.1%. The differential diagnostic efficiency of the combined model was higher than that of the imaging model, and the difference in AUC was statistically significant., Conclusion: The combined model has a higher differential diagnosis efficiency than the imaging model in the differentiation of pulmonary paragonimiasis and tuberculous pleurisy in children. The presence of a tunnel sign on chest CT, the absence of pulmonary nodules, and an elevated percentage of peripheral blood eosinophils are indicative of pulmonary paragonimiasis in children., (© 2024. The Author(s).)

Numerous studies have demonstrated a robust correlation between metabolic syndrome (MetS) and colorectal cancer (CRC). Nonetheless, no systematic analysis or visualization of relevant publications has been conducted via bibliometrics. This research, centred on 616 publications obtainable through the Web of Science Core Collection (WoSCC), employed CiteSpace software and VOSviewer software for correlation analyses of authors, journals, institutions, countries, keywords, and citations. The findings indicate that the Public Library of Science had the highest number of publications, while the United States, China, and South Korea were the most contributory nations. Recent years have seen the mechanisms linking Metabolic Syndrome with Colorectal Cancer, including diet, obesity, insulin resistance, and intestinal flora, remain a burgeoning research area. Furthermore, bariatric surgery appears to be a promising new area of study. This paper presents the initial bibliometric and visualization analysis of research literature concerning CRC and MetS which examines research trends and hotspots., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We previously reported pandemic year (2020) intraoperative middle ear effusion (MEE) rate at time of bilateral myringotomy tube (BMT) placement was 18% lower compared to pre-pandemic year (2019). After mandatory stay at home orders (MSHO) and pandemic social distancing precautions were relaxed, we aimed to assess the impact of a persistent pandemic with new COVID-19 variants on MEE presence during BMT., Methods: This study is a retrospective chart summary exempted by Nemours institutional review board at a single tertiary children's hospital. Children < 18 years who underwent BMT during March 1, 2019-June 31, 2019 (pre-COVID), March 1, 2020-June 31, 2020 (PY1), and March 1, 2021-June 31, 2021 (PY2) were included. Statistical analysis included chi-squared and KruskalWallis., Results: A total of 1069 BMTs were reviewed: 551 (52%) during pre-COVID, 227 (21%) during PY1, and 291 (27%) during PY2. There were no significant differences in age, sex, or BMI across comparison groups. Intraoperative MEE was significantly higher pre-COVID (83%) compared to PY1 (65%) and PY2 (69%) ( P < .001) despite a small rebound in PY2., Conclusion: Intraoperative MEE remains lower in subsequent pandemic years despite relaxed public health measures and may be impacted by persistent public health measures like masking, lower return to daycare, variable social distancing, and/or change to access to health care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022. Methods: A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed. Results: ① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype ( P =0.004, HR =3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points ( P <0.001, HR =2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ ( P <0.001, HR =5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% -80.1% ), P =0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P =0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P =0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively ( P =0.690) . Conclusion: Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient's OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.

Objective: The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored. Methods: A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored. Results: Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS ( P <0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS ( P =0.001, HR =6.981, 95% CI 2.186-22.300; P =0.010, HR =6.719, 95% CI 1.572-28.711; P =0.026, HR =3.386, 95% CI 1.158-9.901; P =0.006, HR =0.151, 95% CI 0.039-0.581) . Conclusion: For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.

Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

Introduction: Sugarcane endophytic nitrogen-fixing bacterium Klebsiella variícola DX120E displayed broad impact on growth, but the exact biological mechanism, especially polyamines (PAs) role, is still meager., Methods: To reveal this relationship, the content of polyamine oxidase (PAO), PAs, reactive oxygen species (ROS)-scavenging antioxidative enzymes, phytohormones, 1-aminocyclopropane-1-carboxylic synthase (ACS), chlorophyll content, and biomass were determined in sugarcane incubated with the DX120E strain. In addition, expression levels of the genes associated with polyamine metabolism were measured by transcriptomic analysis., Results: Genomic analysis of Klebsiella variícola DX120E revealed that 39 genes were involved in polyamine metabolism, transport, and the strain secrete PAs in vitro . Following a 7-day inoculation period, DX120E stimulated an increase in the polyamine oxidase (PAO) enzyme in sugarcane leaves, however, the overall PAs content was reduced. At 15 days, the levels of PAs, ROS-scavenging antioxidative enzymes, and phytohormones showed an upward trend, especially spermidine (Spd), putrescine (Put), catalase (CAT), auxin (IAA), gibberellin (GA), and ACS showed a significant up-regulation. The GO and KEGG enrichment analysis found a total of 73 differentially expressed genes, involving in the cell wall (9), stimulus response (13), peroxidase activity (33), hormone (14) and polyamine metabolism (4)., Discussion: This study demonstrated that endophytic nitrogen-fixing bacteria stimulated polyamine metabolism and phytohormones production in sugarcane plant tissues, resulting in enhanced growth. Dual RNA-seq analyses provided insight into the early-stage interaction between sugarcane seedlings and endophytic bacteria at the transcriptional level. It showed how diverse metabolic processes selectively use distinct molecules to complete the cell functions under present circumstances., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qin, Khan, Yan, Wang, Pan, Huang, Wei, Guo, Li, Dong and Xing.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Organic molecules are of great interest for gas sensing applications. However, achieving high-performance gas sensors with high sensitivity, fast response, low consumption, and workability in humid conditions is still challenging. Herein, we report the rational design and synthesis of an ion-in-conjugation polymer, PADC (poly-4,4'-azodianiline-croconamide), obtained by the condensation of croconic acid with 4-4'diaminoazobenzene for gas sensing under humid conditions. The as-fabricated PADC-based gas sensor exhibits ultrahigh sensitivity (802.7 ppm -1 at 1 ppm), subppb detection limit, and high selectivity under humid air with an 80% humidity effect at a temperature down to 350 K. PADC shows good planarity, excellent thermostability, and a narrow band gap of 1.2 eV because of azobenzene fragments spacing previously repulsed biphenyl rings. Compared to previous humidity immunity works, PADC-based sensors realized humidity immunity at a relatively lower temperature, resulting in lower energy consumption.

Objective: To improve the understanding of the clinical features and imaging characteristics of pregnant women with and without in-vitro fertilisation-embryo transfer combined with pulmonary tuberculosis (TB)., Methods: A retrospective analysis was conducted involving 50 patients with pregnancy who had pulmonary TB and were admitted to the Third People's Hospital of Kunming (China) between 1 January 2017 and 31 December 2021. These patients were divided into an in-vitro fertilisation and embryo transfer (IVF-ET) conception group and a natural conception group according to the conception method. The clinical and imaging data were then collected and compared., Results: The mean age of the IVF-ET group (n = 13, 31.85 ± 5.84 years) was higher than in the natural conception group (n = 37, 27.05 ± 5.5 years). The proportions of fever, haematogenous TB and extrapulmonary TB in the IVF-ET group (92.31%, 84.62% and 76.92%, respectively) were higher than those in the natural conception group (40.54%,16.22%,27.03%,respectively). The percentage of patients with pregnancy who had intracranial TB (76.9%) in the IVF-ET group was higher than in the natural conception group (10.8%). The percentage of pregnancy terminations in the IVF-ET conception group (84.62%) was higher than in the natural conception group (48.65%). All the above results had statistically significant differences (p < 0.05)., Conclusion: Overall, IVF-ET conception combined with extensive pulmonary TB lesions lead to heavy systemic toxic symptoms, severe disease and poor pregnancy outcomes. Therefore, screening for TB prior to performing IVF-ET is recommended., (© 2024. The Author(s).)

Objective: To provide recommendations for a comprehensive management approach for infants and children presenting with symptoms or signs of aspiration., Methods: Three rounds of surveys were sent to authors from 23 institutions worldwide. The threshold for the critical level of agreement among respondents was set at 80 %. To develop the definition of "intractable aspiration," each author was first asked to define the condition. Second, each author was asked to complete a 5-point Likert scale to specify the level of agreement with the definition derived in the first step., Results: Recommendations by the authors regarding the clinical presentation, diagnostic considerations, and medical and surgical management options for aspiration in children., Conclusion: Approach to pediatric aspiration is best achieved by implementing a multidisciplinary approach with a comprehensive investigation strategy and different treatment options., Competing Interests: Declaration of competing interest None declared, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: It is unclear that paired-related homeobox 1 (PRRX1) induces epithelial-mesenchymal transition (EMT) in oesophageal cancer and the specific function of PRRX1 in oesophageal cancer metastasis., Aim: To assess the significance of PRRX1 expression and investigate the mechanism of EMT in oesophageal cancer metastasis., Methods: Detect the expression of PRRX1 by immunohistochemistry in oesophageal tumour tissues and adjacent normal oesophageal tissues; the PRRX1 short hairpin RNA (shRNA) or blank vector lentiviral gene delivery system was transfected into cells; cell proliferation assay, soft agar colony formation assays, cell invasion and migration assays and animal studies were used to observe cells biological characteristics In vitro and in vivo ; XAV939 and LiCl were used to alter the activity of Wnt/β-catenin pathway. Immunofluorescence staining and western blot analysis were used to detect protein expression of EMT markers and Wnt/β-catenin pathway., Results: PRRX1 is expressed at high levels in oesophageal cancer specimens and is closely related to tumour metastasis in patients with oesophageal cancer. Regulation of PRRX1 expression might exert obvious effects on cell proliferation, especially the migration and invasion of oesophageal cancer cells. Moreover, silencing PRRX1 expression using a shRNA produced the opposite effects. In addition, when PRRX1 was overexpressed, inhibition of the Wnt/β-catenin pathway with XAV939 negated the effect of PRRX1 on EMT, whereas when PRRX1 was downregulated, activation of the Wnt/β-catenin pathway with LiCl impaired the effect on EMT., Conclusion: PRRX1 is upregulated in oesophageal cancer is closely correlated with cancer metastasis. Additionally, PRRX1 induces EMT in oesophageal cancer metastasis through activation of Wnt/β-catenin signalling., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) patients with BCR::ABL1 fusion. Methods: The clinical data of seven AML patients with BCR::ABL1 fusion from November 2012 to January 2022 were retrospectively analyzed, and their survival status was followed up. Results: The median age of patients at the time of diagnosis was 35 years. Four cases (57.1%) were diagnosed with high leukocyte counts. All cases were assayed as BCR::ABL1 positive and accompanied by four types of gene mutations (NPM1, RUNX1, ASXL1, PHF6) . Seven patients received tyrosine kinase inhibitor (TKI) combined with induction chemotherapy and bridged to allo-HSCT, and six patients received maintenance therapy with TKI. Before allo-HSCT, six patients achieved complete remission, and four patients achieved complete molecular remission (CMR) . After allo-HSCT, the three remaining cases also achieved CMR. All patients were in remission post-allo-HSCT. One case died of infection, and the remaining cases survived without relapse. The 3-year cumulative overall survival rate was (80.0±17.9) %. Conclusions: TKI combined with traditional chemotherapy could achieve a high response rate in AML patients with BCR::ABL1 fusion. In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.

Objective: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of primary myelofibrosis (PMF) patients. Methods: A total of 14 cases of PMF who underwent allo-HSCT from December 2008 to December 2022 were analyzed retrospectively, including 8 males and 6 females with a median age [ M ( Q 1 , Q 3 )]of 36 (24, 42) years. Three-year overall survival (OS), disease free survival (DFS), cumulative incidence of relapse (CIR), transplantation-related mortality (TRM) were analyzed. Meanwhile, the complications were followed up by telephone and outpatient appointments for 49.6 (9.0,93.1) months. Results: All patients received myeloablative conditioning regimens (MAC). All patients had successful engraftment, and the median time of neutrophils and platelet engraftment were 13.5 (11.8, 18.0) days and 19.5 (13.5, 24.5) days, respectively. Ⅱ-Ⅳ acute graft versus host disease (GVHD) occurred in 3 cases, while chronic GVHD in 8 cases. The rate of 3-year OS,DFS,CIR and TRM were (92.9±6.9)%, (76.0±12.2)%, (38.6±2.7)% and (7.1±0.5)% respectively after a median follow-up time of 1 489.0 (270.3,2 794.8) days. Two patients died from treatment-related complications, one of which died 39 days after transplantation due to heart failure caused by severe anemia, the other patient died 6 years after relapse due to pulmonary infection. Conclusion: Allo-HSCT can be used as a safe and effective approach to treat PMF.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

For colorectal cancer (CRC), surgical resection remains essential for achieving good prognoses. Unfortunately, numerous patients with locally advanced CRC and metastatic CRC failed to meet surgical indications or achieve pathological complete response after surgery. Perioperative therapy has been proven to effectively lower tumor staging and reduce recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have shown unprecedented prolongation of survival time and satisfactory safety in patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR), while the therapeutic effect obtained by patients with mismatch repair-proficient or microsatellite stable (pMMR/MSS) was considered minimal. However, recent studies found that certain CRC patients with dMMR/MSI-H presented intrinsic or acquired immune resistance, and pMMR/MSS CRC patients can also achieve better efficacy. Therefore, more predictors are required for screening patients with potential clinical benefits. Since the discovery of synergistic effects between immunotherapy, chemotherapy, and radiotherapy, different immunotherapy-based therapies have been applied to the perioperative therapy of CRC in an increasing number of research. This review comprehensively summarized the past and current progress of different combinations of immunotherapy in perioperative clinical trials for CRC, focusing on the efficacy and safety, and points out the direction for future development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Zhou, Han, Wei and Qiu.)

To investigate the distribution characteristics of the cyanobacteria community and the driving factors in impounded lakes and reservoirs in Shandong on the east route of the South-to-North Water Diversion Project, monthly samples of phytoplankton and the aquatic environment from Nansi Lake, Dongping Lake, Datun Reservoir, Donghu Reservoir, and Shuangwangcheng Reservoir were collected from May to November during 2010 to 2019. A total of 44 planktonic cyanobacteria taxa were identified with 23 filamentous cyanobacteria taxa. Pseudanabaena limnetica, Cylindrospermopsis raciborskii, Microcystis aeruginosa , and Microcystis wesenbergii were the dominant harmful cyanobacteria species, with a high detection frequency and abundance in all lakes and reservoirs. By analyzing the distribution characteristics of the cyanobacteria community in impounded lakes and reservoirs, we found that filamentous cyanobacteria had growth advantages in the water with large hydraulic disturbances, which should be the key points of cyanobacteria prevention and control in the future. Pearson correlation analysis and generalized linear fitting curve results showed that total nitrogen, total phosphorus, water temperature, and water depth played a key role in affecting the growth of P. limnetica, C. raciborskii, M. aeruginosa , and M. wesenbergii . The nitrogen and phosphorus nutrients could promote the growth of harmful cyanobacteria. Due to the good temperature adaptability, P. limnetica could still become the dominant species in early summer and late autumn, and C. raciborskii, M. aeruginosa , and M. wesenbergii had growth advantages when the water temperature was higher than 25℃. In addition, shallow water was more conducive to the growth of C. raciborskii . It was suggested that based on strengthening of the control of nitrogen and phosphorus nutrient input in lakes and reservoirs, the key monitoring of P. limnetica in lakes should be conducted in early summer and late autumn, and the growth of C. raciborskii in shallow water areas should be paid close attention in the high temperature period to ensure the safety of water quality.

Objective: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC., Subjects and Methods: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC)., Results: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC., Conclusions: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The poor prognosis of hepatocellular carcinoma (HCC) was ascribed to metastasis. Targeted therapy aiming at the molecules along the metastatic pathway is a promising therapeutic strategy. Among them, hydrogen peroxide inducible clone-5 (Hic-5) is highlighted. Hic-5, discovered as a reactive oxygen species (ROS)-inducible gene, was identified to be an adaptor protein in focal adhesion and a critical signaling mediator upregulated in various cancers including HCC. Moreover, Hic-5 may regulate epithelial-mesenchymal transition (EMT) transcription factor Snail and its downstream mesenchymal genes including fibronectin and matrix metalloproteinase-9 required for migration and invasion of HCC. However, the comprehensive Hic-5-mediated pathway was not established and whether Hic-5 can be a target for preventing HCC progression has not been validated in vivo . Using whole-transcriptome mRNA sequencing, we found reactive oxygen species modulator (ROMO) and ZNF395 were upregulated by Hic-5 in a patient-derived HCC cell line, HCC372. Whereas ROMO was involved in Hic-5-mediated ROS signaling, ZNF395 locates downstream of Snail for mesenchymal genes expression required for cell migration. Also, ZNF395 but not ROMO was upregulated by Hic-5 for migration in another patient-derived HCC cell line, HCC374. Further, by in vivo knock down of Hic-5 using the Stable Nucleic Acids Lipid nanoparticles (SNALP)-carried Hic-5 siRNA, progression of HCC372 and HCC374 in SCID mice was prevented, coupled with the decrease of the downstream mesenchymal genes. Our study provides the preclinical evidence that targeting Hic-5 is potentially able to prevent the progression of HCCs with Hic-5 overexpression., Competing Interests: None., (AJCR Copyright © 2023.)

Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P =0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML ( n =10), MDS-AML ( n =6), CMML-AML ( n =1), and MDS ( n =14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

Purpose: To identify factors associated with adherence to radiology follow-up recommendations by the referring physicians., Materials and Methods: In this retrospective study, CT, ultrasound, and MRI reports with the keyword "recommend" and synonyms between March 11, 2019, and March 29, 2019, were included. Emergency department and inpatient examinations and routine surveillance recommendations, such as lung nodules, were excluded. Performance of follow-up examinations was correlated with the strength of recommendation, conditionality of recommendation, direct communication of results to ordering provider, and history of cancer. Outcomes included adherence to recommendations and time to follow-up. Statistical comparison between groups was performed using χ 2 , Kruskal-Wallis, and Spearman correlation., Results: Qualifying recommendations were provided in 255 reports (age 60.1 ± 16.5 years, female: 151 of 255, 59.22%). Imaging follow-up was performed in 166 of 255 (65%) reports: 148 of 166 (89.15%) nonconditional versus 18 of 166 (10.48%) conditional recommendations (P = .008), and more frequently in the patients with a strong follow-up recommendation (138 of 166 [83.13%], versus 28 of 166 [16.86%]) (P = .009). The median time to follow-up was 28 days versus 82 days in patients without versus with a history of cancer (P = .00057), 28 days versus 70 days with direct communication with the provider versus without (P = .0069), 82.5 versus 21 days for reports in which a specific follow-up interval was provided (86 of 255, 33.72%) versus those without (169 of 255, 66.27%) (P < .001)., Conclusion: The adherence rate for radiological nonroutine recommendations was 65%. Reports with strongly worded and nonconditional follow-up recommendations were followed more frequently. Direct communication with providers, patients without a known cancer history, and recommendations with no specified time interval identified were followed up earlier., Clinical Relevance: Strongly worded and nonconditional follow-up recommendations increase the likelihood of follow-up being performed. Direct communication of imaging follow-up recommendations to the provider and lack of specific time intervals decreases the median time to follow-up, which in turn may decrease the delay in medical care., (Published by Elsevier Inc.)

The binding mechanism between tea polyphenols and sturgeon myofibrillar protein (SMP) in the early stage (0, 2, 4 min), middle stage (6, 10 min) and late stage (15 min) of low temperature vacuum heating (LTVH) in an in vitro anti-glycation model was investigated. The result indicated that the protein cross-linking during LTVH treatment were mainly induced by tea polyphenols. The loss rate of free arginine (Arg) and free lysine (Lys) of SMP at the late stage of LTVH treatment (15 min) was 73.95 % and 83.16 %, respectively. The hydrophobic force and disulfide bond were the main force between tea polyphenols and SMP in the middle and late stage of LTVH treatment. The benzene ring and phenolic hydroxyl group of tea polyphenols can interact with the amino acid residues of SMP, which was exothermic and entropy-increasing. This study provides new insights in the interaction mechanisms between tea polyphenols-protein during heat treatment process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To investigate racial and gender-specific microaggressions that are experienced by pediatric otolaryngologists at work., Methods: An anonymous web-based survey consisting of 18 questions was sent to American Society of Pediatric Otolaryngology (ASPO) members via an email link. The survey included questions from the Workplace and School Microaggressions component of the Racial and Ethnic Microaggressions (REM) Scale., Results: 125 out of 610 ASPO members completed the survey for a response rate of 20.5%. 28% of respondents reported experiencing a racial/ethnic microaggression in the last six months. Respondents who identified as Asian American Pacific Islander had significantly higher REM scores when compared with Caucasian respondents (p < 0.05). There was no significant difference in scores when comparing the other Race categories. Female respondents reported significantly higher gendered-microaggression scores compared to those identifying as male (p < 0.001). 66% of female respondents experienced some form of gender-based microaggression in the last six months., Conclusion: By providing evidence that pediatric otolaryngologists continue to report experiences of discrimination in the form of microaggressions, this study aims to increase awareness and inspire a more inclusive work environment., Competing Interests: Declaration of competing interest None. The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The combination of stereotactic body radiation therapy (SBRT) and immune checkpoint inhibitors (ICIs) is actively being explored in advanced non-small-cell lung cancer (NSCLC) patients. However, little is known about the optimal fractionation and radiotherapy target lesions in this scenario. This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs., Methods: The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec. 2015 to Sep. 2021. Patients were grouped according to radiation sites. Progression-free survival (PFS) and overall survival (OS) were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank (Mantel-Cox) test., Results: A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study. Radiation sites included lung lesions (lung group, n=43), bone metastases (bone group, n=24), and brain metastases (brain group, n=57). Compared with the brain group, the mean PFS (mPFS) in the lung group was significantly prolonged by 13.3 months (8.5 months vs. 21.8 months, HR=0.51, 95%CI: 0.28-0.92, P=0.0195), and that in the bone group prolonged by 9.5 months with a 43% reduction in the risk of disease progression (8.5 months vs. 18.0 months, HR=0.57, 95%CI: 0.29-1.13, P=0.1095). The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group. The mean OS (mOS) in the lung and bone groups was longer than that of the brain group, and the risk of death decreased by up to 60% in the lung and bone groups as compared with that of the brain group. When SBRT was concurrently given with ICIs, the mPFS in the lung and brain groups were significantly longer than that of the bone group (29.6 months vs. 16.5 months vs. 12.1 months). When SBRT with 8-12 Gy per fraction was combined with ICIs, the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups (25.4 months vs. 15.2 months vs. 12.0 months). Among patients receiving SBRT on lung lesions and brain metastases, the mPFS in the concurrent group was longer than that of the SBRT→ICIs group (29.6 months vs. 11.4 months, P=0.0003 and 12.1 months vs. 8.9 months, P=0.2559). Among patients receiving SBRT with <8 Gy and 8-12 Gy per fraction, the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group (20.1 months vs. 5.3 months, P=0.0033 and 24.0 months vs. 13.4 months, P=0.1311). The disease control rates of the lung, bone, and brain groups were 90.7%, 83.3%, and 70.1%, respectively., Conclusion: The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients. This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens. Dose fractionation regimens of 8-12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT., (© 2023. Huazhong University of Science and Technology.)

Objective: The purpose of this study is to determine the efficacy of haploidentical donor hematopoietic stem cell transplantation in the treatment of severe aplastic anemia. Methods: The clinical data of 76 patients with severe aplastic anemia (SAA) patients who underwent haplo-HSCT from December 2014 to October 2020 were selectively analyzed. There were 50 males and 26 females with a median age of 16 (3-52) years old. There were 49 SAA-Ⅰ patients, 18 SAA-Ⅱ patients, and 9 patients with hepatitis-associated aplastic anemia. There were 15 cases of bone marrow put together with peripheral blood stem cell transplantation and 61 cases of peripheral blood stem-cell transplantation. Conditioning regimens were Cyclophosphamide (CY) + Fludarabine (Flu) + ATG for 46 patients and Busulfan (Bu) + CY+Flu+ATG for 30 patients. Results: Three patients died during the myelosuppressive phase following transplantation, and 73 patients had a median time of neutrophil engraftment of 12 (9-21) days; in addition to 3 patients who died early, 8 patients did not obtain platelet reconstruction after transplantation, and 65 patients had platelet engraftment with a medium time of 14 (9-90) d. The incidence of primary graft failure was 10.9% and the incidence of secondary graft failure was 5.5%. The incidence of Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) was 38.4%, the incidence of Ⅲ-Ⅳ aGVHD was 16.4%, the incidence of chronic graft anti-host disease (cGVHD) was 35.8%, and the incidence of extensive cGVHD was 22.4%. The medium follow-up time was 19.5 (1-75) months, the prospective overall survival (OS) for 2 years was (78.6±5.0) %, the failure-free survival (FFS) was (75.9±5.1) %, and the transplant-related mortality was (20.2±4.9) %. Multi-factor analysis revealed that the patient older than 35 years old, Ⅲ/Ⅳ aGVHD, HCT-CI≥3, the pre-transplant ferritin ≥1 500 μg/L, the number of neutrophils >1×10(9)/L at the time of onset were risk factors affecting OS ( P =0.008, 0.008, 0.014, 0.004, 0.027) . Patients with graft failure had lower OS and FFS than other patients ( P <0.001) . Conclusion: Haplo-HSCT is an effective method for treating SAA in children, adolescents, and young patients, and the occurrence of severe aGVHD and severe infection, as well as graft failure, are the main causes of survival rate. The prevention and treatment of severe aGVHD and infection are essential to improve efficacy.

Objective: TP53-abnormal MDS/acute myeloid leukemia (AML) patients' allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment's effectiveness and influencing factors should be studied. Methods: 42 patients with TP53 gene status change MDS/AML who underwent allo-HSCT from 2014.8.1 to 2021.7.31 at the Hematology Hospital of the Chinese Academy of Medical Sciences were the subject of a retrospective analysis. The 42 patients were divided into three groups: the TP53 deletion group (group A) , TP53 mono-alle mutation group (group B) , and TP53 multi-hit group (group C) . The differences in clinical features and prognostic factors after transplantation were analyzed. Results: There were 42 MDS/AML patients, including 21 patients with MDS, and 21 patients with AML. The median follow-up period was 34.0 (7.5-75.0) months and the median patient age at the time of transplantation was 41.5 (18-63) years old. The total OS was 66.3% (95% CI 53.4%-82.4%) in 3 years after transplantation, and EFS was 61.0% (95% CI 47.7%-78.0%) in 3 years. For 3 years after receiving hematopoietic stem cell transplantation, there were no statistically significant differences in 3-year OS and EFS in groups A, B, and C ( P ≥0.05) . The 3 years OS was 82.5% (95% CI 63.1%-100.0%) in group A, 60.6% (95% CI 43.5%-84.4%) in group B, and 57.1% (95% CI 30.1%-100.0%) in group C. Univariate analysis revealed that the number of co-mutant genes, pre-HSCT treatment, and disease type did not affect prognosis, while age, karyotype, co-mutation, positive blast cell before transplantation, and positive blast cell after transplantation were common prognostic factors for OS and EFS ( P <0.1) . MRD levels before transplantation were found to be independent risk factors for OS ( P =0.037, HR =33.40, 95% CI 1.24-901.17) in a multivariate analysis. Conclusion: Patients with MDS/AML who have TP53 mutations can benefit from allo-HSCT, but patients with complex karyotypes have a worse prognosis. Meanwhile, the final flow cytometry (FCM) monitoring blast cell test before HSCT has a certain guiding significance for prognostic assessment.

Objective: To examine the comparative effectiveness of magnetic resonance imaging-ultrasound (MRI-U/S) fusion biopsy and in-bore MRI-targeted biopsy., Methods: We identified men aged 18-89 with a diagnosis of elevated prostate specific antigen (PSA) or Gleason 6 prostate cancer on active surveillance who underwent MRI-U/S fusion prostate biopsy (12-core + targeted) in the office or in-bore MRI-targeted biopsy (MRI-IB; targeted only). The cancer detection rate (CDR; Gleason 6-10) and clinically significant CDR (csCDR; Gleason 7-10) were compared across biopsy techniques, adjusted for patient and radiographic features., Results: A total of 280 patients (346 lesions) were included, of whom 23.9% were on active surveillance for Gleason 6 prostate cancer. In the per-patient analyses, there was no statistically significant difference in adjusted overall CDR (64.1% vs 54.2%; P = .24) or csCDR (36.5% vs 37.9%; P = .85) between MRI-U/S and MRI-IB biopsy. In the per-lesion analyses, there was no statistically significant difference in adjusted overall CDR (45.7% vs 50.1%; P = .49) between MRI-U/S and MRI-IB biopsy, but MRI-IB biopsy was associated with a higher csCDR than MRI-U/S biopsy (32.8% vs 21.4%; P = .02)., Conclusion: We observed no statistically significant differences in cancer detection rates between MRI-U/S fusion biopsy and MRI-IB biopsy in per-patient analyses. However, MRI-IB biopsy was associated with higher csCDR when considering targeted biopsy cores only. These results suggest that systematic cores should be obtained when performing MRI-U/S fusion biopsy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia., Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4-12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8., Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (-0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly ( p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group ( p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group., Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia., Competing Interests: The authors declare that they have no relevant financial interests., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Cholangiocarcinoma (CCA) is a malignant neoplasm of the bile ducts, being the second most common type of cancer in the liver, and most patients are diagnosed at a late stage with poor prognosis. Targeted therapy aiming at receptors tyrosine kinases (RTKs) such as c-Met or EGFR have been developed but with unsatisfactory outcomes. In our recent report, we found several oncogenic molecules downstream of RTKs, including hydrogen peroxide clone-5 (Hic-5), Src, AKT and JNK, were elevated in tissues of a significant portion of metastatic CCAs. By inhibitor studies and a knockdown approach, these molecules were found to be within the same signal cascade responsible for the migration of HuCCT1 cells, a conventionally used CCA cell line. Herein, we also found Src inhibitor dasatinib and Hic-5 siRNA corporately suppressed HuCCT1 cell invasion. Moreover, dasatinib inhibited the progression of the HuCCT1 tumor on SCID mice skin coupled with decreasing the expression of Hic-5 and EGFR and the activities of Src, AKT and JNK. In addition, we found a glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and several cytoskeletal molecules such as tubulin and cofilin were dramatically decreased after a long-term treatment of the HuCCT1 tumor with a high dose of dasatinib. Specifically, GAPDH was shown to be a downstream effector of the Hic-5/Src/AKT cascade involved in HuCCT1 cell migration. On the other hand, TFK1, another CCA cell line without Hic-5 expression, exhibited very low motility, whereas an ectopic Hic-5 expression enhanced the activation of Src and AKT and marginally increased TFK1 migration. In the future, it is tempting to investigate whether cotargeting Src, Hic-5 and/or GAPDH is efficient for preventing CCA progression in future clinical trials.

Context: Coronavirus disease 2019 is a global pandemic. Studies suggest that folic acid has antiviral effects. Molecular docking shown that folic acid can act on SARS-CoV-2 Nucleocapsid Phosphoprotein (SARS-CoV-2 N)., Objective: To identify novel molecular therapeutic targets for SARS-CoV-2., Materials and Methods: Traditional Chinese medicine targets and virus-related genes were identified with network pharmacology and big data analysis. Folic acid was singled out by molecular docking, and its potential target SARS-CoV-2 N was identified. Inhibition of SARS-CoV-2 N of folic acid was verified at the cellular level., Results: In total, 8355 drug targets were potentially involved in the inhibition of SARS-CoV-2. 113 hub genes were screened by further association analysis between targets and virus-related genes. The hub genes related compounds were analysed and folic acid was screened as a potential new drug. Moreover, molecular docking showed folic acid could target on SARS-CoV-2 N which inhibits host RNA interference (RNAi). Therefore, this study was based on RNAi to verify whether folic acid antagonises SARS-CoV-2 N. Cell-based experiments shown that RNAi decreased mCherry expression by 81.7% ( p  < 0.001). This effect was decreased by 8.0% in the presence of SARS-CoV-2 N, indicating that SARS-CoV-2 N inhibits RNAi. With increasing of folic acid concentration, mCherry expression decreased, indicating that folic acid antagonises the regulatory effect of SARS-CoV-2 N on host RNAi., Discussion and Conclusions: Folic acid may be an antagonist of SARS-CoV-2 N, but its effect on viruses unclear. In future, the mechanisms of action of folic acid against SARS-CoV-2 N should be studied.

Endophytic nitrogen-fixing bacteria are versatile and widely distributed in plants. Numerous strains of endophytic nitrogen-fixing bacteria are used as biofertilizers to minimize the utilization of chemical fertilizers, improve nutrient use efficiency, increase crop productivity, and reduce environmental pollution. However, the mechanism underlying the interaction between nitrogen-fixing bacteria and plants is still unclear. So, the present study was planned to assess the effects of endophytic nitrogen-fixing bacteria on sugarcane by analyzing the changes in physiological and biochemical activities. In the current study, Klebsiella variicola DX120E, an endophytic nitrogen-fixing bacterium, was inoculated on sugarcane varieties B8 and ROC22 to evaluate the effects on nitrogen and carbon metabolism-related enzymatic activity and biomass. Results showed that DX120E inoculation improved the enzymatic activities related to gluconeogenesis and nitrogen metabolism increased the sugarcane plant's height, cane juice Brix, biomass, chlorophyll, and soluble sugar content in sugarcane. Metabolomics analysis revealed that the metabolome modules were highly enriched in carbon and nitrogen metabolic pathways of strain-affected sugarcane than uninoculated control. The identified carbohydrates were associated with the glycolysis or gluconeogenesis and tricarboxylic acid (TCA) cycle in plants. Metabolomic profiling in the present investigation showed that carbohydrate metabolism is coordinated with nitrogen metabolism to provide carbon skeletons and energy to amino acid synthesis, and amino acid degradation results in several metabolites used by the citric acid cycle as an energy source. Moreover, differentially expressed metabolites of non-proteinogenic amino acids have a further complementary role to the action of endophytic nitrogen-fixing bacteria. Meanwhile, a significant difference in metabolites and metabolic pathways present in stems and leaves of B8 and ROC22 varieties was found. This study discovered the potential benefits of DX120E in sugarcane and suggested candidate regulatory elements to enhance interactions between nitrogen-fixing microbes and sugarcane., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Xie, Khan, Wei, Sun, Su, Guo, Li and Xing.)