Bacillus velezensis DJ1 exhibits broad-spectrum antagonistic activity against diverse phytopathogenic fungi, while its biocontrol mechanisms against Fusarium graminearum, the causal agent of maize stalk rot, remain poorly characterized. In this study, we integrated genomics and transcriptomics to elucidate the antifungal mechanisms of strain DJ1. The results demonstrated that DJ1 inhibited F. graminearum with the efficacy of 64.4%, while its polyketide crude extract achieved the control efficacy of 55% in pot experiments against this disease. Whole-genome sequencing revealed a single circular chromosome (3 929 792 bp, GC content of 47%) harboring 12 biosynthetic gene clusters for secondary metabolites, six of which encoded known antimicrobial compounds (macrolactin H, bacillaene, difficidin, surfactin, fengycin, and bacilysin). Transcriptomic analysis identified 243 differentially expressed genes (152 upregulated and 91 downregulated, P < 0.05), which were potentially associated with the antagonistic activity against F. graminearum. KEGG enrichment analysis highlighted activation (P < 0.05) of cysteine/methionine metabolism, pentose phosphate pathway, and polyketide biosynthesis pathways, indicating that DJ1 employed synergistic strategies involving antimicrobial compound synthesis, energy metabolism enhancement, and nutrient competition to suppress pathogens. This study provides a theoretical foundation for developing novel microbial resources and application technologies to combat phytopathogenic fungi.
Fusarium/drug effects* ; Bacillus/metabolism* ; Plant Diseases/prevention & control* ; Antifungal Agents/pharmacology* ; Genomics ; Zea mays/microbiology* ; Transcriptome ; Gene Expression Profiling ; Antibiosis ; Multigene Family ; Multiomics

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule via specific secondary structures. Compared to antibody-drug conjugates (ADC), aptamer‒drug conjugate (ApDC) is also an efficient, targeted drug for cancer therapy with a smaller size, higher chemical stability, lower immunogenicity, faster tissue penetration, and facile engineering. Despite all these advantages, several key factors have delayed the clinical translation of ApDC, such as in vivo off-target effects and potential safety issues. In this review, we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.

Objective:To explore the changes of hip joint function in patients with total hip arthroplasty (THA) within three months after operation, and to explore the impact of fear of falling on hip joint function recovery.Methods:From December 2020 to August 2021, 205 patients with THA after operation in the Xinjiang Uygur Municipal People's Hospital were selected as the study subject by objective sampling. The patients were investigated with the General Information Questionnaire, the Chinese version of Falls Efficacy Scale-International (FES-I) , and the Harris Hip Score after the first activity out of bed, one month and three months after operation. Pearson correlation was used to analyze the correlation between the scores of FES-I in Chinese version and the scores of Harris Hip Score in different periods after operation, and multiple linear regression were used to analyze the influencing factors of hip joint function recovery in different periods after operation.Results:After the first activity out of bed, one month and three months after operation, the FES-I scores of 205 patients after THA were (32.24±6.05) , (30.94±6.04) and (28.48±3.52) respectively, and the scores of Harris Hip Score were (61.49±8.92) , (72.58±5.52) and (89.15±5.70) respectively, and the correlation analysis showed that they were negatively correlated ( r=-0.512, -0.523, -0.549; P<0.05) . The results of multiple linear regression analysis showed that age and fear of falling were the influencing factors for the hip joint function recovery when THA patients got out of bed for the first time after operation ( P<0.05) , which could explain 31.2% of the total variation. Sex, age, number of concomitant diseases and fear of falling were the influencing factors of hip joint function recovery in THA patients one month after operation ( P<0.05) , which could explain 43.7% of the total variation. Sex, age, number of concomitant diseases and fear of falling were the influencing factors of hip joint function recovery in THA patients three months after operation ( P<0.05) , which could explain 36.9% of the total variation. Conclusions:The recovery of hip joint function in THA patients shows an overall upward trend three months after operation. The impact of fear of falling on the recovery of hip joint function in different periods persists. The higher the level of fear of falling, the worse the recovery of hip joint function. Nurses should evaluate the patients' fear of falling at different periods after operation, and strengthen the attention and guidance to patients with high fear of falling, elderly patients, and patients with other diseases, so as to promote the recovery of patients' joint function.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Objective To determine the serum IgM and IgG antibody levels post-COVID-19 vaccination， and provide scientific evidence for COVID-19 antibody response after vaccination. Methods A total of 980 healthy persons were included in Kunming Third People’s Hospital from July through August， 2021， which had been vaccinated with COVID-19 vaccines and then tested for anti-SARS-CoV-2 IgM and IgG antibodies. Results After the COVID-19 vaccination， 469 persons （positive rate， 47.86%） were positive for anti-IgG antibody. Of them， 75 were males with （positive rate， 39.06%）， and the average IgG level was 0.618 （0.180， 2.526） AU·mL^-1［M（Q₁，Q₃）］； 394 were females （50.00%）， and the IgG level was 0.999 （0.305， 3.334） AU·mL^-1. In addition， 53 persons （5.41%） were anti-IgM antibody positive. Of them， 14 were males （positive rate， 7.29%）， and the average IgM level was 0.057 （0.026， 0.195） AU·mL^-1； 39 were females （4.95%）， and the IgM level was 0.047 （0.027， 0.110） AU·mL^-1. The positive rate of anti-IgG antibody was highest in those aged ≤30 years， which was 51.02% in male （n=25） and 55.88% in female （n=133）. The anti-IgG response differed significantly by gender （χ²=7.401， D=0.135 1， P<0.05）， whereas the anti-IgM response was not significantly different （χ²=1.656， P>0.05）. Among the age groups， anti-IgG antibody level was higher in those aged ≤30 and 51-70 years， with 158 （55.05%） and 122 （52.36%） persons， respectively； the average antibody level was 1.209 （0.426， 4.386） AU·mL^-1 and 1.074 （0.191， 7.670） AU·mL^-1， respectively. The differences in the positive rates of IgG and IgM antibodies and the levels of IgG antibodies among different age groups were statistically significant （P<0.05）. Using Kruskal-Wallis test and Spearman correlation analysis， it showed a high correlation between the IgG and IgM antibodies （r=0.836 4， H=64.82， 20.09， P<0.05）. Conclusion The Anti-SARS-CoV-2 IgG antibody remains high six months post-COVID-19 vaccination， while anti-IgM antibody is low. The IgM and IgG response are higher in the young and elderly. The response differs by gender and age， demonstrating a correlation.

Objective To study mechanical properties of the novel micro-movement elastic implant of distal tibiofibular syndesmosis in dorsiflexion position.Methods A combination of simulation and experiment was used. The normal ankle dorsiflexion model, the bone nail repaired model and the micro-movement elastic implant repaired model were established by using Mimics and CT data. Besides, ANSYS Workbench was used for finite element analysis. Mechanical experiments on lower limb specimens were conducted on Instron E10000 mechanical test instrument, and five sets of experimental data were measured and analyzed.Results Mechanical properties of the micro-movement elastic implant repaired model were closer to those of the normal ankle dorsiflexion model, but stress of the micro-movement elastic implant repaired mode was greater than that of the bone nail repaired model. The results of two-sample heteroscedasticity t test indicated that there was no significant difference in resistance torque between the micro-movement elastic implant repaired model and the normal ankle dorsiflexion model.Conclusions For dorsiflexion position, repairing mechanical properties of the novel micro-movement elastic implant are much better than those of the bone nail, and there is still room for optimizing the micro-movement elastic implant.

Objective:To explore the changing trends and influencing factors of AIDS-related and non-AIDS-related deaths after receiving antiretroviral therapy (ART) among HIV-positive individuals in Dehong Dai Jingpo autonomous prefecture (Dehong) from 2010 to 2019.Methods:Based on the Chinese National treatment database, HIV patients who initiated ART from 2010 to 2019 were included in the analysis. The cumulative incidence function was used to estimate the cumulative incidence of AIDS-related death and non-AIDS-related death, respectively. The Fine-Grey model was used to compare the differences between AIDS-related and non-AIDS-related deaths and analyze its influencing factors.Results:A total of 7 068 HIV-positive individuals were included, of which 388 were AIDS-related deaths and 570 were non-AIDS-related deaths. The cumulative mortality rate at years 1, 2, 3, 4, 5, 7 and 9 after receiving ART were 2.27%, 3.46%, 4.47%, 5.03%, 5.84%, 6.61%, 7.40% for AIDS-related deaths, and 1.63%, 3.11%, 4.68%, 6.02%, 7.42%, 10.49%, 12.75% for non-AIDS-related deaths, respectively. In the Fine-Grey model, older age at ART initiation, male, unmarried, injection drug use as the transmission route, lower baseline BMI, lower baseline CD4 + T cell counts, baseline FIB-4 score >3.25, and baseline anemia were risk factors for AIDS-related death. In contrast, age at ART initiation ≥45 years, male, Dai, and Jingpo minority ethnicities, unmarried, injection drug use as the transmission route, lower baseline BMI, baseline FIB-4 score >3.25, baseline eGFR <60 ml·min -1·1.73 m -2, and baseline anemia were risk factors for non-AIDS-related deaths. Conclusions:The cumulative mortality rate was low among HIV-positive individuals after receiving ART in Dehong during 2010-2019. The mortality of non-AIDS-related deaths was higher than that of AIDS-related deaths. There were also differences in the factors influencing AIDS-related and non-AIDS-related deaths and interventions should be intensified to target the influencing factors for non-AIDS-related deaths.

Objective:To investigate the incidence of anemia and risk factors in HIV/AIDS patients with access to antiretroviral therapy (ART) during 2004-2018 in Dehong Jingpo and Dai Autonomous Prefecture (Dehong).Methods:A retrospective cohort study was conducted in HIV/AIDS patients receiving ART in Dehong during 2004-2018 based on the data extracted from the National HIV/AIDS antiretroviral therapy database. Cox proportional risk model was used to analyze the factors associated with the incidences of anemia and moderate or severe anemia in the HIV/AIDS patients. And the piecewise linear mixed-effects model was used to depict the trajectory of hemoglobin changes over time after initiating ART according to baseline level.Results:A total of 8 044 HIV/AIDS patients were included, in whom 6 337 (78.8%) were without anemia at baseline survey and had a median follow up time of 4.43 ( P 25, P 75: 1.50, 6.71) years. The median follow up time for 1 291 new anemia cases and 293 new moderate or severe anemia cases was 0.16 ( P 25, P 75: 0.07, 1.99) years and 0.48 ( P 25, P 75:0.09, 2.97) years, respectively. The incidence rate of anemia and moderate or severe anemia was 4.40 per 100 person-years and 0.41 per 100 person-years respectively. In multivariable Cox regression analysis, older age, being female, being in Dai and Jingpo ethnic group, baseline BMI <18.5 kg/m 2, baseline CD4 +T lymphocyte cell counts (CD4) <200 cells/μl, and zidovudine (AZT) -based initial treatment regimen were factors significantly and positively associated with incidence of anemia after treatment. Factors as being female, being in Dai ethnic group, baseline BMI <18.5 kg/m 2, mild baseline anemia, and AZT-based initial treatment regimen were significantly and positively associated with incidence of moderate or severe anemia after treatment. Conclusion:The risk for anemia was higher in HIV/AIDS patients with specific characteristics, such as age ≥60 years , being female, being in Dai and Jingpo ethnic groups, lower BMI, CD4 <200 cells/μl, and treatment of AZT, after initiation of ART in Dehong during 2004-2018. Additional efforts are needed to strengthen the screening, prevention and treatment of anemia in this population.

Objective:To evaluate the performance of the Cepheid Xpert Xpress Flu/RSV assay (Xpert) in the detection of children infected with influenza virus (Flu) or respiratory syncytial virus (RSV).Methods:Nasopharyngeal specimens were collected from children who showed symptoms of respiratory infection and tested FluA, FluB and RSV by Xpert and sequencing assay respectively side by side. Discordant result were tested with a laboratory-developed real-time PCR for resolution.Results:A total of 388 nasopharyngeal swabs (NAPs) from children with acute respiratory tract infection were analyzed and the result showed 91.75-94.85% agreement between two tests. The sensitivity of FluA, FluB and RSV detected by Xpert and sequencing assay were 99.21% (125/126) vs. 92.86% (117/126), 100.00% (109/109) vs. 84.40% (92/109) and 100.00% (52/52) vs. 40.38% (21/52), respectively. The specificity of FluA, FluB and RSV detected by Xpert were all lower than that of the sequencing assay: 95.42% (250/262) vs 99.24% (260/262), 99.28% (277/279) vs 99.64% (278/279) and 99.70% (335/336) vs 100.00% (336/336). The positive predictive values (PPV) of FluA, FluB and RSV detected by Xpert were lower than those of the sequencing assay: 91.30% (126/138) vs. 98.33% (118/120), 98.18% (108/110) vs. 98.92% (92/93) and 98.11% (52/53) vs. 100.00% (21/21), respectively. The negative predictive values (NPV) of FluA, FluB and RSV detected by Xpert were higher than those of the sequencing assay: 99.60% (251/252) vs. 96.67% (261/270), 99.64% (279/280) vs. 94.27% (280/297) and 100.00% (337/337) vs. 91.60% (338/369).Conclusions:The Cepheid Xpert Xpress Flu/RSV assay is a sensitive, reliable and rapid assay for the detection of FluA, FluB and RSV in pediatrics.