The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Background With the events reporting on odors in drinking water, odorous substances in water have become a hot topic in water quality analysis. Due to the low concentration of the odor threshold and the complexity of the odor components in water, it is difficult to make accurate qualitative and quantitative analysis. So it is necessary to develop a highly sensitive and accurate qualitative and quantitative analysis method. Objective To establish a method for simultaneous determination of four odorous substances, including dimethyl disulfide, dimethyl trisulfide, 2-methylisoborneol, and geosmin in water by purge and trap-gas chromatography-tandem mass spectrometry. Methods A certain amount of water sample was stored in the sample vial of a purge and trapinstrument. Through nitrogen purging, the odorous substances in water were purged out and enriched in the trap. Subsequently, the odorous substances were rapidly released at high temperatures after heating the trap, and then carried by carrier gas into gas chromatograph. After temperature programming, the substances were separated by an Agilent DB-624 capillary chromatographic column (30 m×0.25 mm, 1.4 μm) and determined by tandem mass spectrometry in multiple reaction monitoring modes, with internal standard method for quantification. The current project optimized purge time, sodium chloride concentration in water sample, desorption temperature, desorption time, and split ratio during the experimental process. Under the optimized experimental conditions, the standard curve, detection limit, and quantification limit were validated. Recovery tests with spiking concentrations of 5.0, 10.0, 30.0, 80.0 ng·L⁻¹ and precision tests were conducted on water samples. Finally, the established method was applied to detect odorous substances in source water, finished water, and pipeline water in Deqing County of Huzhou City. Result After the optimization, the purge time was 20 min, the desorption temperature was 280 ℃, the desorption time was 2 min, the split ratio was 10∶1, and no sodium chloride was added during the purge process. Under the optimized experimental conditions, the calibration curves for the four odorous substances showed an excellent linearity in the range of 1 to 100 ng·L⁻¹ (R>0.999), with 0.3 ng·L⁻¹ limit of detection and 1.0 ng·L⁻¹ limit of quantitation. The average recoveries were from 85.5% to 102.4% and relative standard deviations (RSD) from 1.6% to 5.2%. After applying this method to detect local source water, finished water, and pipeline water, it was found that the positive rates of 2-methylisoborneo, and geosmin were relatively high, while the positive rates of dimethyl disulfide and dimethyl trisulfide were relatively low. Only one sample of source water tested positive for dimethyl disulfide, and all samples were negative for dimethyl trisulfide. Conclusion Combined with the superiority of purge and trap and tandem mass spectrometry, the method has the advantages of easy to perform, strong anti-interference ability, good accuracy and precision, which meet the limit requirements of the four odorous substances in the expanded indices and reference indices of Hygienic standards for drinking water (GB 5749-2022). It also provides technical support for water quality assessment and analysis of odorous substances.

Cancers are significant diseases that seriously threaten human health.Accurate diagnosis and efficacy assessment are the keys to improving clinical treatment and reducing cancer-related mortality.With the further development of artificial intelligence in medical imaging,radiomics and pathomics have emerged and shown great potential in diagnosing and treating cancers.However,at the same time,radiomics and pathomics have also shown their limitations of lacking biological validation and macroscopic properties of cancers,respectively.Combining them across modalities and scales is necessary to complement each other's strengths.This paper reviewed the progress,limitations,and future perspectives of radiomics and pathomics workflows and their combined application in cancers.

Objective:To evaluate pulmonary hypertension (PH) in Chinese people living with human immunodeficiency virus (HIV) receiving long-term anti-retroviral therapy (ART) and those who had not received ART for HIV infection, and to analyze the risk factors for PH in HIV infected individuals, so as to provide evidence for the monitoring and management of cardiovascular diseases in people living with HIV in China.Methods:HIV infected individuals who received long-term ART were from the NCT04463810 study cohort. In addition, using propensity score matching method, gender matched HIV infected individuals who had not received ART were selected as controls from the NCT00872417 and NCT01844297 studies. This study was a retrospective and observational clinical study. Basic data, clinical visit and cardiac Doppler ultrasonography data were collected to analyze the prevalence of PH and risk factors for PH in people living with HIV. Chi-square test and multivariate logistic regression were used for statistical analysis.Results:Among the 318 HIV infected individuals, 159 underwent long-term ART and 159 did not receive ART, which were divided into long-term ART group and ART-na?ve group, respectively. Among 318 HIV infected individuals, 30 cases (9.4%) experienced PH, including 23 cases (7.2%) with critical PH, six cases (1.9%) with mild PH, one case (0.3%) with moderate PH, and there was no severe PH. The prevalence of PH in the long-term ART group was 5.0%(8/159), which was lower than that in the ART-na?ve group (13.8%, 22/159). The difference was statistically significant ( χ2=7.21, P=0.012). Multivariate analysis showed that older age (odds ratio ( OR)=1.064, 95% confidence interval ( CI) 1.019 to 1.111, P=0.016) and unsuppressed HIV status ( OR=2.660, 95% CI 1.041 to 6.797, P=0.041) were independent risk factors for PH of people living with HIV. Conclusions:The prevalence of PH in people living with HIV with long-term ART is lower than that of ART-na?ve people living with HIV. Older age and unsuppressed HIV status are independent risk factors for PH in people living with HIV. Cardiac Doppler ultrasonography is helpful for the early screening of PH in people living with HIV. ART should be actively performed to reduce the incidence of PH in people living with HIV.

Objective:To explore the effect of multidisciplinary management combined with 60-second high-risk diabetic foot screening in diabetic foot.Methods:From January to December 2022, 138 patients with diabetic foot were selected from Xinxiang Central Hospital by convenience sampling. The patients were randomly divided into a control group and an observation group, with 69 cases in each group. Control group implemented routine follow-up management of diabetic foot, and observation group carried out multidisciplinary management combined with 60-second high-risk diabetic foot screening on the basis of control group, and the intervention lasted for six months. The progress of Wagner grading of diabetic foot and foot self-care were compared between the two groups.Results:After intervention, the number of Wagner grading progression patients in observation group and control group was four cases (5.80%) and 10 cases (14.49%), respectively. The number of progression patients in observation group was less than that in control group, and the difference was statistically significant (χ 2=4.161, P=0.041). The total score and dimension scores of diabetic foot self-management in the two groups after the intervention were higher than those before the intervention, but only the scores of observation group before and after the intervention were statistically significant ( P<0.05). After intervention, the total score and dimension scores of diabetic foot self-management in observation group were higher than those in control group, with a statistically significant difference ( P<0.05) . Conclusions:Multidisciplinary management combined with 60-second high-risk diabetic foot screening can effectively delay the progress of diabetic foot and improve patients' foot self-care.

Practice teaching is an important link in the training of public health talents in colleges and universities. At present, there are still some problems in the education of public health and preventive medicine in the colleges and universities in China, such as attaching greater importance to theory than to practice and weak training of practical skills among students. In view of this situation, a public health practice teaching model of "internal-external interactions" has been constructed in Dalian Medical University with focuses on the following aspects: ①experiments in the university are optimized based on social needs; ②the practice base outside the university is expanded based on the teaching in the university; ③"internal-external interactions" are adopted to enhance practice training and improve post competence. The teaching practice shows that the implementation of the teaching model of "internal-external interactions" can help to improve practice teaching ability, promote the improvement in the training quality of public health talents, and meet the social demand for application-oriented professionals.

AIM: To explore schisandrin B (Sch B) pretreatment reduces intestinal ischemia reperfusion injury (IIRI) through inhibiting apoptosis by activation of Nrf2/HO-1 signing pathway in mice by network pharmacology and in vivo experiment. METHODS: (1) The targets of Sch B and IIRI were searched from online databases, Drawing Venn diagram to obtain the common target of them. Cytoscape software was imported to construct the protein-protein interaction (PPI) network to establish the "Drugs-Disease-core target gene" network. The mechanism of Sch B against IIRI was predicted through GO and KEGG enrichment analysis. (2) Thirty-six C57BL/6J mice were randomly divided into six groups (n = 6). The model of IIRI was established in four groups except the sham operation group. Three of the groups were pretreated with Sch B, Nrf2 inhibitor ML385, and Sch B + ML385, respectively. After the experiment, intestinal tissue samples were taken for HE staining, Chiu ' s score, apoptosis staining, immunohistochemistry (IHC), and immunoblotting (Western blot). RESULTS: A total of 412 Sch B related tar- gets, 2 166 IIRI related targets and 153 common targets were screened out through network pharmacology. There were 88 "Sch B-IIRI-core target gene" included NFE2L2 (Nrf2), HMOX1 (HO-1), BCL2, CASP3 (caspase 3), and so on. KEGG enrichment analysis screened 163 related pathways, apoptosis pathway ranked high showing that the pathway may play a key role in the treatment of IIRI by Sch B. The animal experiment had shown that Sch B reduced the Chiu's score and apoptotic while upregulating Nrf2, HO-1, Bcl-2 protein expression levels and Bcl-2/Bax, downregulating Bax, and cleaved caspase-3 expression levels, thereby reducing IIRI in mice, and that Nrf2 inhibitor ML385 reversed this process (P < 0.05). CONCLUSION: This study reveals that Sch B has the characteristics of multi-target and multi-pathway in the reduction of IIRI, and Sch B can reduce IIRI through inhibiting apoptosis by activation of Nrf2/ HO-1 pathway.

AIM: To verify the role of tetramethylpyrazine (TMP) in intestinal ischemia-reperfusion (I/ R) injury and its relationship with pyroptosis. METHODS: Thirty-six healthy SPF male C57BL / 6 mice, 8-12 weeks old, weighing 20-25 g, were divided into six groups randomized by table of random number (n = 6/group): Sham group (S1 group)Ischemia/reperfusion group (I/R1 group), I/R + TMP treatment group: 15 mg/kg (T15 group), 30 mg/kg (T30 group), 60 mg/kg (T60-1 group), 120 mg/kg (T120 group). In experiment 2, thirty healthy SPF male C57BL/6 mice were divided into five groups (n = 6/group): Sham group (S2 group), I/R group (I/ R2 group), I/R + dimethyl sulphoxide (DMSO) group (DMSO group), I/R + TMP (60 mg/kg) group (T60-2 group), and I/R + DMSO + TMP (60 mg/kg) + Nigericin sodium salt (NSS) group (T60+NSS group). I/R-induced intestinal injury was established by clamping the superior mesenteric artery for 45 minutes, followed by 120 minutes of reperfusion, while the sham group mice underwent isolation of superior mesenteric artery without clamping. An NLRP3 agonist NSS was dissolved in DMSO, was intraperitoneally injected (4 mg/kg) 60 minutes before ischemia. And DMSO group mice were intraperitoneally administered with corresponding DMSO. Different TMP dosage groups and T60+NSS group mice were intraperitoneally administered with TMP 30 minutes before ischemia. IL-1β and IL-18 concentrations in the intestine were measured at 120 minutes after reperfusion by ELISA. The pathological changes of the sections were observed by optical microscope, and the intestinal mucosal injury was evaluated by Chiu's score grading. Western blot was used to detect NLRP3, Caspase-1, and GSDMD in intestinal tissue. RESULTS: Statistically significant increase of Chiu's score, IL-1β, IL-18 concentrations in the I/R1 group were found as compared with S1 group (P<0.05). And compared with I / R1 group, Chiu's score and IL-1β, IL-18 concentrations in the T60-1, T120 groups were reduced (P<0.05). Moreover, Chiu's score in the T120 group was lower than that in the T60 group (P<0.05). We found a statistically significant increase of Chiu's score and IL-1β, IL-18 concentrations and the expression of NLRP3, GSDMD, caspase-1 in the I/R group (P<0.05) as compared with S2 group. Compared with I / R2 group, Chiu's score, IL-1β, IL-18 concentrations and NLRP3, GSDMD, caspase-1 expression in the T60-2 group was reduced (P<0.05). Compared with T60-2 group, Chiu's score, IL-1β, IL-18 concentrations and NLRP3, GSDMD, caspase-1 expression in the T60 + NSS group were upregulated (P<0.05). CONCLUSION: The protective effect of TMP against intestinal I / R injury was dose-dependent. And TMP can decrease pyroptosis mainly by inhibiting the activation of the NLRP3 inflammasome.

Objective:To examine the association between macrophage migration inhibitory factor(MIF), Interleukin 6(IL-6), periodontal disease, and atherosclerosis in middle-aged and elderly individuals.Methods:This cross-sectional study enrolled 700 diabetic patients who were attending the endocrinology department of Beijing Hospital from January 2020 to December 2022.Out of these patients, 491 underwent a full-mouth periodontal examination.Among them, 106 were middle-aged and elderly.The study included 83 patients with complete data, aged between 45 and 70 years(mean age: 58.2±8.7 years).Among the included patients, 48 were male(57.8%)and 35 were female(42.2%).A questionnaire was administered to gather information about the patients, and serum levels of MIF and IL-6 were measured using enzyme-linked immunosorbent assay(ELISA).The relationship between serum MIF and IL-6 levels and periodontitis and atherosclerosis was evaluated through univariate and multifactorial analyses conducted on middle-aged and elderly individuals.Results:There were 66 cases(79.5%)in the periodontitis stage Ⅰ/Ⅱ group and 17 cases(20.5%)in the stage Ⅲ/Ⅳ group.The serum MIF levels in the two groups were(2, 312.5±795.0)ng/L and(2, 939.8±665.0)ng/L, respectively( P<0.01).Similarly, IL-6 levels were(3.5±3.0)ng/L and(6.7±6.1)ng/L in the two groups( P>0.05).The findings revealed that for each 1 ng/L increase in MIF serum levels, the risk of severe periodontitis and increased carotid intima-media thickness(cIMT)increased by 0.1%.Furthermore, for each 1 ng/L increase in serum MIF and IL-6 levels, the risk increased by 0.2% and 38.9% respectively.Serum MIF levels were found to be associated with atherosclerosis as well as with various factors related to periodontitis, including periodontal probing depth, bleeding index, clinical attachment level, periodontal probing depth≥4 mm sites, clinical attachment level≥5%, and bleeding index >2%(all P<0.05). Conclusions:This study investigates the correlation between MIF and IL-6 levels with Periodontal disease and Atherosclerosis in middle-aged and elderly individuals.