[Current status of palliative care for patients with unresectable metastatic colorectal cancer in China: a questionnaire-based survey].

Objective: To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China. Methods: From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis. Results: A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0-1. After receiving third- and fourth-line treatment, 50%-60% of patients maintained a good quality of life and 40%-50% of them maintained ECOG performance scores of 0-1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer. Conclusions: This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.

[Porphyromonas gingivalis infection facilitates immune escape of esophageal cancer by enhancing YTHDF2-mediated Fas degradation].

OBJECTIVE: To investigate the effect of Porphyromonas gingivalis (Pg) infection on immune escape of oesophageal cancer cells and the role of YTHDF2 and Fas in this regulatory mechanism. METHODS: We examined YTHDF2 and Fas protein expressions in esophageal squamous cell carcinoma (ESCC) tissues with and without Pg infection using immunohistochemistry and in Pg-infected KYSE150 cells using Western blotting. The interaction between YTHDF2 and Fas was investigated by co-immunoprecipitation (Co-IP). Pg-infected KYSE150 cells with lentivirus-mediated YTHDF2 knockdown were examined for changes in expression levels of YTHDF2, cathepsin B (CTSB), Fas and FasL proteins, and the effect of E64 (a cathepsin inhibitor) on these proteins were observed. After Pg infection and E64 treatment, KYSE150 cells were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the expressions of T cell-related effector molecules were detected by flow cytometry. RESULTS: ESCC tissues and cells with Pg infection showed significantly increased YTHDF2 expression and lowered Fas expression. The results of Co-IP demonstrated a direct interaction between YTHDF2 and Fas. In Pg-infected KYSE150 cells with YTHDF2 knockdown, the expression of CTSB was significantly reduced while Fas and FasL expressions were significantly increased. E64 treatment of KYSE150 cells significantly decreased the expression of CTSB without affecting YTHDF2 expression and obviously increased Fas and FasL expressions. Flow cytometry showed that in Pg-infected KYSE150 cells co-cultured with PBMCs, the expressions of Granzyme B and Ki67 were significantly decreased while PD-1 expression was significantly enhanced. CONCLUSION: Pg infection YTHDF2-dependently regulates the expression of Fas to facilitate immune escape of esophageal cancer and thus promoting cancer progression, suggesting the key role of YTHDF2 in regulating immune escape of esophageal cancer.

The predictive value of estimated pulse wave velocity (ePWV) combined with BMI for newly diagnosed diabetes.

PURPOSE: Estimated pulse wave velocity (ePWV) and body mass index (BMI) are significant predictors of new-onset diabetes. This study aims to evaluate the impact and predictive value of combining ePWV and BMI on the incidence of new-onset diabetes. METHODS: A secondary analysis was conducted on a cohort study by Rich Healthcare (China), involving 211,833 eligible participants. Logistic regression analysis identified factors influencing diabetes occurrence, while ROC curve analysis assessed the predictive value of ePWV, BMI, and their combination for new-onset diabetes. RESULTS: Over a mean follow-up period of 3.12 years, 3,000 men (1.41%) and 1,174 women (0.55%) were diagnosed with diabetes. Logistic regression revealed that BMI, triglycerides, alanine aminotransferase, blood urea nitrogen, creatinine clearance rate, ePWV, and family history of diabetes are high-risk factors for new-onset diabetes. The combination of ePWV and BMI provided a higher area under the ROC curve (0.822) compared to ePWV or BMI alone. CONCLUSION: Elevated levels of ePWV and BMI are independent risk factors for new-onset diabetes. Combining these measures enhances predictive accuracy compared to using either indicator alone.

[Evaluation of disinfection effect of high-energy pulse ultraviolet disinfection equipment in medical institution settings].

Objective: To evaluate the disinfection effect of high-energy pulse ultraviolet disinfection equipment in medical institution settings. Methods: The disinfection effect was evaluated through field tests and laboratory tests. Among them, 135 high-frequency contact points were selected from nine departments in the field test. Samples were collected before and after disinfection, and the disinfection effects of 75% alcohol wipes wiping disinfection, high-energy pulse ultraviolet disinfection robot disinfection and high-energy pulse ultraviolet handheld disinfection instrument were compared. In the laboratory test, 30 infected areas of the simulated test table were exposed to vertical ultraviolet irradiation and the bacterial-killing rate before and after disinfection was calculated. Results: In the field test, the bacteria-killing rates of 75% alcohol wipes, high-energy pulse ultraviolet disinfection robot and high-energy pulse ultraviolet handheld disinfection instrument were 94.99%, 91.53% and 95.94%, respectively, and the difference was statistically significant. The disinfection effect of the high-energy pulse ultraviolet handheld disinfection instrument was better than that of the high-energy pulse ultraviolet disinfection robot (P values <0.05). In the laboratory test, the killing log value of Staphylococcus aureus and Escherichia coli on the carrier were both greater than 3.00. In the simulated field test, the killing log value of Staphylococcus aureus on the surface samples were 4.99. Conclusion: Both the high-energy pulse ultraviolet handheld disinfection instrument and the high-energy pulse ultraviolet disinfection robot have good disinfection effects, which are similar to the disinfection effects of conventional 75% alcohol wipes.

Investigating the Impact of Tea Consumption on Cognitive Function and Exploring Tea-Genetic Interactions in Older Adults Aged 65-105 Years: Findings from the 2002-2018 CLHLS Data.

BACKGROUND: As the global population ages, cognitive impairment (CI) becomes more prevalent. Tea has been one of the most popular drinks in the world. Several studies have demonstrated that tea consumption has an impact on cognitive function. OBJECTIVE: This study aims to examine the association between tea consumption and cognitive function and explore the potential effect of genetics on the relationship between tea consumption and CI risk in older adults. DESIGN: This is a prospective longitudinal study using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). SETTING: Six waves of data from CLHLS containing 76,270 subjects were analyzed. Generalized estimation equations (GEE) with a logit link function were adopted to estimate the effect of tea consumption on CI risk from a cross-sectional and longitudinal perspective. PARTICIPANTS: A population-based cohort of adults aged 65-105 years. MEASUREMENTS: The frequency and type of tea consumption were obtained by questionnaires. CI was measured based on MMSE. Polygenic risk was measured using the polygenic score approach described by the International Schizophrenia. RESULTS: The results showed that drinking green tea had a better protective effect on cognitive function than other types of tea, the incidence of CI gradually decreased with the increase of tea consumption frequency, and men were more likely to benefit from tea consumption. Additionally, we also found a significant interaction between tea consumption and genetic risk, measured by polygenic risk score (PRS). CONCLUSIONS: Based on current research evidence, tea consumption, may be a simple and important measure for CI prevention.

Beneficial Effects of High-Intensity Interval Training and Dietary Changes Intervention on Hepatic Fat Accumulation in HFD-Induced Obese Rats.

Lifestyle intervention encompassing nutrition and physical activity are effective strategies to prevent progressive lipid deposition in the liver. This study aimed to explore the effect of dietary change, and/or high-intensity interval training (HIIT) on hepatic lipid accumulation in high fat diet (HFD)-induced obese rats. We divided lean rats into lean control (LC) or HIIT groups (LH), and obese rats into obese normal chow diet (ND) control (ONC) or HIIT groups (ONH) and obese HFD control (OHC) or HIIT groups (OHH). We found that dietary or HIIT intervention significantly decreased body weight and the risk of dyslipidemia, prevented hepatic lipid accumulation. HIIT significantly improved mitochondrial fatty acid oxidation through upregulating mitochondrial enzyme activities, mitochondrial function and AMPK/PPARalpha/CPT1alpha pathway, as well as inhibiting hepatic de novo lipogenesis in obese HFD rats. These findings indicate that dietary alone or HIIT intervention powerfully improve intrahepatic storage of fat in diet induced obese rats. Keywords: Obesity, Exercise, Diet, Mitochondrial function, Lipid deposition.

[New 2023 global definition of acute respiratory distress syndrome: progress and limitation].

Acute respiratory distress syndrome (ARDS) presents a challenge in clinical diagnosis as it lacks a definitive gold standard. Over the past 55 years, there have been several revisions to the definition of ARDS. With the progress of clinical practice and scientific research, the limitations of the "Berlin definition" have become increasingly evident. In response to these changes, the 2023 global definition of ARDS aims to address these issues by expanding the diagnostic targets, chest imaging, and methods for assessing hypoxia. Additionally, the new definition increases the diagnostic criteria to accommodate resource-constrained settings. The expansion facilitates early identification and treatment interventions for ARDS, thereby advancing epidemiological and clinically related research. Nevertheless, the broad nature of this revision may include patients who do not actually have ARDS, thus raising the risk of false-positive diagnoses. Therefore, additional verification is crucial to ascertain the validity and accuracy of the 2023 global definition of ARDS.

[Research progress on the mechanism of action of heme oxygenase-1 regulating ferroptosis in non-alcoholic fatty liver disease].

Non-alcoholic fatty liver disease (NAFLD) has gradually become the most prevalent chronic liver disease in the world, but its pathogenesis has not been fully elucidated. Ferroptosis is a novel type of programmed cell death caused by iron-dependent lipid peroxidation. Heme oxygenase-1 is a recognized antioxidant enzyme and an important regulatory factor in ferroptosis that modulates ferroptosis through various pathways and, in turn, regulates NAFLD. This paper reviews the regulatory mechanism of heme oxygenase-1 on NAFLD in ferroptosis pathway, with a view to clarifying the occurrence and development mechanisms of NAFLD and providing new vision and targets for its prevention and treatment.

[Effects of different types of intraocular lens implantation on patient's visual quality and function after phacoemulsification].

Objective: To explore the effects of different types of intraocular lens (IOL) implantation on patient's visual quality and function after phacoemulsification. Methods: The clinical data of patients with monocular cataract who underwent phacoemulsification in the Department of Ophthalmology, People's Hospital Affiliated to Shandong First Medical University between December 2021 and May 2023 were retrospectively analyzed. According to the types of IOL, the patients were divided into monofocal group, bifocal group and depth of focus extension group. Three months later, uncorrected distance visual acuity (UCDVA), best corrected distance visual acuity (BCDVA), uncorrected intermediate visual acuity (UCIVA), best corrected intermediate visual acuity (BCIVA), uncorrected near visual acuity (UCNVA) and best corrected near visual acuity (BCNVA) were detected. Contrast sensitivity and total wavefront aberration were measured by visual function analyzer. Satisfaction with visual quality was evaluated by hospital-made satisfaction questionnaire. Results: A total of 92 patients were included, with 31 males and 61 females, and their age was (61.8±5.2) years. There were 43, 28 and 21 cases in monofocal group, bifocal group and depth of focus extension group, respectively. No statistically significant difference was found in clinical baseline data among the three groups. UCIVA, UCDVA, BCIVA and BCDVA in depth of focus extension group were 1.01±0.13, 0.92±0.18, 1.21±0.19 and 1.20±0.23, respectively, which were higher than those in monofocal group (0.62±0.12, 0.74±0.13, 1.02±0.17, 1.07±0.19, respectively) and bifocal group (0.67±0.15, 0.78±0.14, 1.01±0.16, 1.01±0.18, respectively), while absolute value of spherical equivalent [(-0.42±0.07) D] was lower than that in the other two groups [ (-0.49±0.05) D and (-0.45±0.08) D] (both P<0.05). UCNVA and BCNVA in bifocal group were 0.91±0.18 and 1.25±0.18, which were higher than those in depth of focus extension group (0.63±0.24 and 1.19±0.17) (both P<0.05). There were no significant differences in contrast sensitivity among the three groups under day vision or between monofocal group and bifocal group under night vision (all P>0.05), but the contrast sensitivity was higher in depth of focus extension group under night vision (3.0, 6.0, 12.0 c/d) than other two groups (all P<0.05). The score of ocular discomfort was the highest in bifocal group, followed by depth of focus extension group and monofocal group (both P<0.05). The score of visual interference in bifocal group was lower than that in monofocal group and depth of focus extension group (both P<0.05). The scores of subjective feeling in bifocal group and depth of focus extension group were higher than that in monofocal group (both P<0.05). The reading score was the highest in bifocal group, followed by depth of focus extension group and monofocal group (both P<0.05). There was no significant difference in total low-order aberration among the three groups (P=0.472). The total aberration and higher-order aberration [(0.74±0.35) µm and (0.41±0.12) µm] were the highest in monofocal group, followed by bifocal group [(0.61±0.21) µm and (0.22±0.09) µm] and depth of focus extension group [(0.46±0.13) µm and (0.06±0.09) µm] (all P<0.05). Conclusions: IOL implantation with depth of focus extension can enhance visual range, night vision and contrast sensitivity, and thus effectively improve postoperative visual quality and function in cataract patients. The bifocal IOL can better improve the patient's UCNVA and BCNVA, resulting in high satisfaction with visual quality.

[Challenges and solutions in current human leukocyte antigen confirmatory typing of hematopoietic stem cell transplantation].

The impact of human leukocyte antigen (HLA) on hematopoietic stem cell transplantation (HSCT) necessitates high precision in HLA genotyping. Confirmatory typing for patients and their related or unrelated donors before HSCT is critical. This study seeks to standardize HLA confirmatory typing in laboratories by examining the current state of HLA genotyping in the country, building upon the National Standards and Industrial Standards for HLA, and highlighting the significance of confirmatory typing for patients and potential donors prior to HSCT. A retrospective analysis over a decade reveals initial typing errors, indicating potential issues and critical considerations in pre-analytical, analytical, and post-analytical stages. Problems are attributed to three main causes: (1) random human errors, including technical mistakes, sample mix-up, and transcription inaccuracies; (2) limitations of technical methods, such as the varied sequence ranges between confirmatory and initial typing; (3) patient factors, involving high tumor burden, the influence of certain drugs on HLA genotyping results, and the second transplantation. Solutions are proposed for these problems, along with recommendations to standardize HLA confirmatory typing.

[Establishment and validation of prediction models for human leukocyte antigen haplotypes and human leukocyte antigen genotypes].

Objective: To establish prediction models for human leukocyte antigen (HLA) haplotypes and HLA genotypes, and verify the prediction accuracy. Methods: The prediction models were established based on the characteristic of HLA haplotype inheritance and linkage disequilibrium (LD), as well as the invention patents and software copyrights obtained. The models include algorithm and reference databases such as HLA A-C-B-DRB1-DQB1 high-resolution haplotypes database, B-C and DRB1-DQB1 LD database, G group alleles table, and NMDP Code alleles table. The prediction algorithm involves data processing, comparison with reference data, filtering results, probability calculation and ranking, confidence degree estimation, and output of prediction results. The accuracy of the predictions was verified by comparing them with the correct results, and the relationship between prediction accuracy and the probability distribution and confidence degree of the predicted results was analyzed. Results: The HLA haplotypes and genotypes prediction models were established. The prediction algorithm included the prediction of A-C-B-DRB1-DQB1 haplotypes according to HLA-A, B, DRB1, C, DQB1 genotypes, the prediction of C and DQB1 high-resolution results according to A, B and DRB1 high-resolution results, and the prediction of A, B, DRB1, C and DQB1 high resolution results according to the A, B and DRB1 intermediate or low resolution results. Validation results of "Predicting A-C-B-DRB1-DQB1 haplotypes basing on HLA-A, B, DRB1, C, DQB1 genotypes" model: for 787 data, the accuracy was 94.0% (740/787) with 740 correct predictions, 34 incorrect predictions, and 13 instances with no predicted results. For 847 data, the accuracy was 100% (847/847). The 2 411 and 2 594 haplotype combinations predicted from 787 and 847 data were grouped according to confidence degree, the accuracy was 100% (48/48, 114/114) for a confidence degree of 1, 96.2% (303/315) and 97.8% (409/418) for a confidence degree of 2 respectively. Validation results of "Predicting A, B, DRB1 and C, DQB1 high-resolution genotypes basing on HLA-A, B, DRB1 high, intermediate, or low resolution genotypes" model: when predicting C and DQB1 high resolution genotypes basing on A, B, and DRB1 high resolution genotypes, 89.3% (1 459/1 634) of the predictions were correct. The accuracy for the top 2 predicted probability (GPP) ranking was 79.2% (1 156/1 459), and for the top 10, it was 95.0% (1 386/1 459). Furthermore, when GPP≥90% and GPP 50%-90%, the prediction accuracy was 81.3% (209/257) and 72.8% (447/614) respectively. The accuracy of predicting C and DQB1 high resolution genotypes basing on the results of A, B, and DRB1 high resolution genotypes from the China Marrow Donor Program was 87.0% (20/23). The accuracy of predicting A, B, DRB1, C, and DQB1 high resolution genotypes basing on the results of A, B, and DRB1 intermediate or low-resolution genotypes was 70.0% (7/10) and 52.5% (21/40) respectively. When predicting whether the patient is likely to have a HLA 10/10 matched donor, the accuracy of the top 2 GPP combinations with a proportion of ≥50% was 85.7% (6/7). Conclusions: When using A, B, DRB1, C, DQB1 genotypes to predict A-C-B-DRB1-DQB1 haplotype combinations, the results with a confidence degree of 1 and 2 are reliable. When predicting C and DQB1 genotypes according to A, B and DRB1 genotypes, the top 10 results ranked by GPP are reliable, and the top 2 results with GPP≥50% are more reliable.

[Establishing and verifying the threshold value of HLA mixed antigen reagent screening test results].

Objective: To establish the threshold value of human leukocyte antigen (HLA) mixed antigen reagent screening test results, and to verify it by HLA single antigen reagent confirmation test results. Methods: The results of 2 255 serum samples tested for HLA antibodies by HLA mixed antigen reagent in the department of HLA Laboratory, the First Affiliated Hospital of Soochow University from October 2017 to December 2021 were retrospectively analyzed. Among them, 1 139 samples were also tested by single antigen HLA Class-Ⅰ reagent and 1 116 samples were also tested by single antigen HLA Class-Ⅱ reagent. Based on the same antigens coated with both reagents, the Mean Fluorescence Intensity (MFI) and Nomalized Background ratio (NBG ratio) of 12 HLA Class-Ⅰ beads and 5 HLA Class-Ⅱ beads in the HLA mixed antigen reagent and the MFI of 77 anti-HLA class-Ⅰ antibodies and 35 anti-HLA class-Ⅱ antibodies detected by HLA single antigen reagent were recorded. The MFI and NBG ratio of HLA mixed antigen reagent beads in 1 139 or 1 116 samples were segmented according to the positive rate of antibodyies detected by the single antigen reagent corresponding to the antigens coated with each HLA mixed antigen reagent bead, and the results of the HLA mixed antigen screening test were verified by the HLA single antigen reagent confirmation test. Results: The threshold values of MFI and NBG ratio of HLA mixed antigen reagent's 17 beads were established. The MFI of No. 1 to No. 17 beads of HLA mixed antigen reagent ranged from 26.86 to 21 925.58, and the NBG ratio ranged from 0 to 434.65. According to the positive detection rate of HLA single antigen reagent corresponding to the coated antigens, the MFI and NBG ratio of the beads of HLA mixed antigen reagent were divided into positive interval, suspicious positive interval, suspicious negative interval and negative interval. The positive rates of anti-HLA class-Ⅰ antibodies by HLA mixed antigen reagent and single antigen HLA Class-Ⅰ reagent were 87.5% (997/1 139) and 66.3% (755/1 139). The positive rates of anti-HLA class-Ⅱ antibodies were 63.4% (707/1 116) and 44.9% (501/1 116). In the samples with suspicious negative, suspicious positive and positive results of HLA class-Ⅰ、Ⅱ antibodies detected by HLA mixed antigen reagent, the positive detection rates of single antigen HLA Class-Ⅰ reagent were 14.9% (17/114), 41.3% (145/351) and 91.3% (590/646), respectively. The positive detection rates of single antigen HLA Class-Ⅱ reagent were 15.5% (58/375), 26.5% (81/306) and 88.8% (356/401), respectively. Conclusions: In this study, the threshold values of MFI and NBG ratio of HLA mixed antigen reagent screening test are established, and the threshold values are verified by the results of HLA single antigen reagent confirmation test. HLA mixed reagent screening test can be used for screening of HLA antibodies, and if necessary, it should be combined with HLA single antigen confirmatory test for clinical detection of HLA antibodies.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Spectral modulation of high-order harmonics in relativistic laser-solid interaction.

Spectral modulation of high-order harmonics generated in relativistic laser-solid interaction is investigated. Numerical simulations show that the modulation depends on surface plasma density profile, resulting in spectral envelope modulation and regular and irregular harmonic splitting. The mathematical and physical connections between the spectral modulation of high-order harmonics and the temporal modification of attosecond pulse train are explained. Based on these understandings, we propose a possible method to produce isolated attosecond pulses by tailoring surface the plasma profile.

[OCT analysis of in-stent neointima over 5 years post-DES implantation].

Objective: To investigate the characteristics of neointimal hyperplasia (NIH) in patients with in-stent restenosis (ISR) over 5 years post-drug-eluting stent (DES) implantation based on optical coherence tomography (OCT). Methods: In this cross-sectional study, patients with DES-ISR who underwent OCT examination at PLA General Hospital between March 2010 and March 2022 were retrospectively included. All patients were divided into≤5 years DES-ISR group and>5 years DES-ISR group according to the time interval after DES implantation. Quantitative and qualitative analyses were conducted on OCT images to compare the clinical data and lesion characteristics of two patient groups. Furthermore, the independent clinical predictive factors of in-stent neoatherosclerosis (ISNA) were analyzed by multivariable logistic regression. Results: A total of 230 DES-ISR patients with 249 lesions were included, with an age of (63.1±10.4) years and 188 males (81.7%). The median interval after DES implantation was 6 (2, 9) years. There were 117 patients (122 ISR lesions) in the≤5 years DES-ISR group, and 113 patients (127 ISR lesions) in the>5 years DES-ISR group. Compared with≤5 years DES-ISR,>5 years DES-ISR showed more heterogeneous patterns (65.4% (83/127) vs. 48.4% (59/122), P=0.007), diffuse patterns (46.5% (59/127) vs. 31.2% (38/122), P=0.013), macrophage accumulations (44.1% (56/127) vs. 31.2% (38/122), P=0.035) in NIH and higher prevalence of ISNA (83.5% (106/127) vs. 72.1% (88/122), P=0.031). According to multivariable logistic regression, the independent predictive factor for ISNA was female (OR=0.44, 95%CI 0.21-0.90, P=0.026). Female (OR=0.48, 95%CI 0.23-0.99, P=0.046) and low-density lipoprotein cholesterol level (OR=1.62, 95%CI 1.01-2.59, P=0.046) were independent predictive factors, respectively, for lipid ISNA. Calcified ISNA was independently associated with time interval of post-DES implantation (OR=1.18, 95%CI 1.07-1.29, P=0.001). Conclusion: DES-ISR patients with a time interval of>5 years after stent implantation have a higher prevalence of ISNA and more complex lesions. Gender, the level of low-density lipoprotein cholesterol, and the time interval post-DES implantation are independently correlated with ISNA, lipid ISNA, and calcified ISNA.

Asociación entre la velocidad estimada de onda de pulso y la muerte por todas las causas en pacientes con insuficiencia cardiaca / Association between estimated pulse wave velocity and all-cause death in patients with heart failure

Antecedentes La arteriosclerosis ha demostrado ser un factor de riesgo para el desarrollo de insuficiencia cardiaca y readmisión. ePWV es un indicador novedoso, no invasivo y simple de la rigidez arterial, y este estudio tiene como objetivo investigar su relación con la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Métodos Este estudio es un estudio de cohorte que incluyó a 1.272 pacientes con insuficiencia cardiaca de los datos de NHANES de 1999 a 2018. El ePWV se dividió en tres grupos y se calculó la tasa de mortalidad acumulada de pacientes con insuficiencia cardiaca utilizando curvas de supervivencia de KM. La relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca se representó mediante un ajuste de curva suavizado. Se utilizó análisis de regresión de COX para evaluar la asociación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Resultados La edad promedio de la población del estudio fue de 67,8±12,6 años, con 862 hombres y 650 mujeres. Durante el período de seguimiento de 12 meses, hubo 790 casos de mortalidad por todas las causas. Se utilizó un análisis de regresión de Cox para validar la relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Los pacientes con niveles más altos de ePWV tendían a tener una tasa de mortalidad por todas las causas más alta. Después del ajuste de múltiples factores, un aumento en ePWV se asoció positivamente con la tasa de mortalidad por todas las causas (HR=1,17, intervalo de confianza [IC] del 95%: 1,12-1,22). En comparación con el tercil más bajo, la HR ajustada por múltiples variables y el IC del 95% para el tercil más alto de ePWV fueron 1,81 (IC del 95%: 1,45-2,27)... (AU)

Background Arteriosclerosis has been proven to be a risk factor for the development of heart failure and readmission. ePWV is a novel non-invasive and simple indicator of arterial stiffness, and this study aims to investigate its relationship with all-cause mortality rate in patients with heart failure. Methods This study is a cohort study that included 1272 patients with heart failure from NHANES data from 1999 to 2018. The ePWV was divided into three groups, and the cumulative mortality rate of heart failure patients was calculated using KM survival curves. The relationship between ePWV and all-cause mortality rate in heart failure patients was represented by a smoothed curve fitting. COX regression analysis was used to assess the association between ePWV and all-cause mortality rate in heart failure patients. Results The average age of the study population was 67.8±12.6 years, with 862 males and 650 females. During the 12-month follow-up period, there were 790 cases of all-cause mortality. Cox regression analysis was used to validate the relationship between ePWV and all-cause mortality rate in patients with heart failure. Patients with higher levels of ePWV tended to have a higher all-cause mortality rate. After adjustment for multiple factors, an increase in ePWV was positively associated with all-cause mortality rate (HR=1.17, 95% confidence interval [CI]: 1.12-1.22). Compared to the lowest tertile, the multivariable-adjusted HR and 95%CI for the highest tertile of ePWV were 1.81 (95%CI: 1.45-2.27). Additionally, a smoothed curve fitting was used to observe the relationship between ePWV and mortality rate, where the curve demonstrated a positive correlation between ePWV and all-cause mortality rate. Furthermore, KM survival curves indicated that all-cause mortality rate increased with the increase in ePWV. Subgroup analysis suggested a correlation between ePWV and mortality rate... (AU)

Asociación entre la velocidad estimada de onda de pulso y la muerte por todas las causas en pacientes con insuficiencia cardiaca / Association between estimated pulse wave velocity and all-cause death in patients with heart failure

Antecedentes La arteriosclerosis ha demostrado ser un factor de riesgo para el desarrollo de insuficiencia cardiaca y readmisión. ePWV es un indicador novedoso, no invasivo y simple de la rigidez arterial, y este estudio tiene como objetivo investigar su relación con la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Métodos Este estudio es un estudio de cohorte que incluyó a 1.272 pacientes con insuficiencia cardiaca de los datos de NHANES de 1999 a 2018. El ePWV se dividió en tres grupos y se calculó la tasa de mortalidad acumulada de pacientes con insuficiencia cardiaca utilizando curvas de supervivencia de KM. La relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca se representó mediante un ajuste de curva suavizado. Se utilizó análisis de regresión de COX para evaluar la asociación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Resultados La edad promedio de la población del estudio fue de 67,8±12,6 años, con 862 hombres y 650 mujeres. Durante el período de seguimiento de 12 meses, hubo 790 casos de mortalidad por todas las causas. Se utilizó un análisis de regresión de Cox para validar la relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Los pacientes con niveles más altos de ePWV tendían a tener una tasa de mortalidad por todas las causas más alta. Después del ajuste de múltiples factores, un aumento en ePWV se asoció positivamente con la tasa de mortalidad por todas las causas (HR=1,17, intervalo de confianza [IC] del 95%: 1,12-1,22). En comparación con el tercil más bajo, la HR ajustada por múltiples variables y el IC del 95% para el tercil más alto de ePWV fueron 1,81 (IC del 95%: 1,45-2,27)... (AU)

Background Arteriosclerosis has been proven to be a risk factor for the development of heart failure and readmission. ePWV is a novel non-invasive and simple indicator of arterial stiffness, and this study aims to investigate its relationship with all-cause mortality rate in patients with heart failure. Methods This study is a cohort study that included 1272 patients with heart failure from NHANES data from 1999 to 2018. The ePWV was divided into three groups, and the cumulative mortality rate of heart failure patients was calculated using KM survival curves. The relationship between ePWV and all-cause mortality rate in heart failure patients was represented by a smoothed curve fitting. COX regression analysis was used to assess the association between ePWV and all-cause mortality rate in heart failure patients. Results The average age of the study population was 67.8±12.6 years, with 862 males and 650 females. During the 12-month follow-up period, there were 790 cases of all-cause mortality. Cox regression analysis was used to validate the relationship between ePWV and all-cause mortality rate in patients with heart failure. Patients with higher levels of ePWV tended to have a higher all-cause mortality rate. After adjustment for multiple factors, an increase in ePWV was positively associated with all-cause mortality rate (HR=1.17, 95% confidence interval [CI]: 1.12-1.22). Compared to the lowest tertile, the multivariable-adjusted HR and 95%CI for the highest tertile of ePWV were 1.81 (95%CI: 1.45-2.27). Additionally, a smoothed curve fitting was used to observe the relationship between ePWV and mortality rate, where the curve demonstrated a positive correlation between ePWV and all-cause mortality rate. Furthermore, KM survival curves indicated that all-cause mortality rate increased with the increase in ePWV. Subgroup analysis suggested a correlation between ePWV and mortality rate... (AU)

[Application progress of clinical outcome assessment measures in patients with gastric cancer].

Gastric cancer is a common tumor of the gastrointestinal tract, and the global trend in morbidity and mortality are not encouraging. Especially in advanced gastric cancer, patient survival outcome is an essential clinical concern and a vital outcome indicator in clinical outcome assessment. This article reviews the definition of clinical outcome assessment and the measurement tools that can be applied in gastric cancer patients, describes the detailed classification of clinical outcome assessment tools, and reviews the current status of the application of clinical outcome assessment in gastric cancer, analyzing the effects and shortcomings of its application, to provide a reference for the clinical staff in choosing the appropriate tools, and assisting in the comprehensive and holistic assessment of clinical outcomes for the promotion of the development of precision medicine.

[Efficacy and safety analysis of the zanubrutinib-based bridging regimen in chimeric antigen receptor T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma].

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.

[Efficacy and safety of fourth-generation CD19 CAR-T expressing IL7 and CCL19 along with PD-1 monoclonal antibody for relapsed or refractory large B-cell lymphoma].

Objective: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Methods: Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. Results: All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Conclusion: Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.