Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine：Fibromyalgia Syndrome / 中国实验方剂学杂志

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.

The regulatory role of the RUS family in plant growth and development / 生物工程学报

The chloroplast genome encodes many key proteins involved in photosynthesis and other metabolic processes, and metabolites synthesized in chloroplasts are essential for normal plant growth and development. Root-UVB (ultraviolet radiation B)-sensitive (RUS) family proteins composed of highly conserved DUF647 domain belong to chloroplast proteins. They play an important role in the regulation of various life activities such as plant morphogenesis, material transport and energy metabolism. This article summarizes the recent advances of the RUS family proteins in the growth and development of plants such as embryonic development, photomorphological construction, VB6 homeostasis, auxin transport and anther development, with the aim to facilitate further study of its molecular regulation mechanism in plant growth and development.

Preparation and in vitro evaluation of polylactic acid nanoparticles containing arginine and glucose oxidase / 药学学报

Hydrogen peroxide (H2O2) and nitric oxide (NO) has a short half-life, low bioavailability, poor tumor targeting and systemic adverse reactions in the physiological environment. In this study, phacoemulsification and nano-precipitation were used to synthesize didecyl dimethyl ammonium bromide (DDAB)/polylactic acid nanoparticles (PLA), then L-arginine (L-Arg) and glucose oxidase (GOx)-loaded nanoparticles (GADP) were prepared, and the in vitro antitumor activity was investigated．The particle size, potential, embedding rate and the ability to produce H2O2/NO of the nanoparticles were investigated. Meanwhile, in vitro cell cytotoxicity against human hepatoma cells (HepG2) was evaluated．The results showed that the prepared L-Arg-DDAB/PLA (ADP) nanoparticles were spherical particles. And the particle size and zeta potential were (225.7 ± 6.33) nm and (+23.5 ± 0.12) mV, respectively. The adsorption rate of GOx was 87.23% ± 0.02%. The drug loading of L-Arg was 15.6% ± 0.22%. The pH value of glucose solution and the amount of H2O2 showed that GADP had good catalytic activity. In vitro cytotoxicity experiments showed that blank nanoparticles were nontoxic, while the drug-loaded nanoparticles presented enhanced antitumor effect on HepG2 cells. And can inhibit tumor cell migration. The low dose nano-scale NO delivery system GADP can effectively inhibit the migration of tumor cells and kill tumor cells, thus producing therapeutic benefits.

Diagnosis and treatment of the portal vein complications for children undergoing spilt liver transplantation / 器官移植

Objective To investigate the diagnosis and treatment strategy of the portal vein complications in children undergoing split liver transplantation. Methods The clinical data of 88 pediatric recipients who underwent split liver transplantation were retrospectively analyzed. Intraoperative anastomosis at the bifurcating site of the portal vein or donor iliac vein bypass anastomosis was performed depending on the internal diameter and development of the recipient's portal vein. A normalized portal venous blood stream monitoring was performed during the perioperative stage. After operation, heparin sodium was used to bridge warfarin for anticoagulation therapy. After portal vein stenosis or thrombosis was identified with enhanced CT or portography, managements including embolectomy, systemic anticoagulation, interventional thrombus removal, balloon dilatation and/or stenting were performed. Results Among the 88 recipients, a total of 10 children were diagnosed with portal vein complications, of which 4 cases were diagnosed with portal vein stenosis at 1 d, 2 months, 8 months, and 11 months after surgery, and 6 cases were diagnosed with portal vein thrombosis at intraoperative, 2 d, 3 d (n=2), 6 d, and 11 months after surgery, respectively. One patient with portal vein stenosis and one patient with portal vein thrombosis died perioperatively. The fatality related to portal vein complications was 2% (2/88). Of the remaining 8 patients, 1 underwent systemic anticoagulation, 2 underwent portal venous embolectomy, 1 underwent interventional balloon dilatation, and 4 underwent interventional balloon dilatation plus stenting. No portal venous related symptoms were detected during postoperative long term follow up, and the retested portal venous blood stream parameters were normal. Conclusions The normalized intra- and post-operative portal venous blood stream monitoring is a useful tool for the early detection of portal vein complications, the early utilization of useful managements such as intraoperative portal venous embolectomy, interventional balloon dilatation and stenting may effectively treat the portal vein complications, thus minimizing the portal vein complication related graft loss and recipient death.

Finite element analysis of cervical intervertebral discs after removing different ranges of uncinate processes / 解剖学报

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

Diagnosis and treatment pathway of neoadjuvant immunotherapy for esophageal cancer in Henan province / 中国胸心血管外科临床杂志

@#Esophageal cancer is a highly prevalent tumor species in Henan province, which brings heavy medical burden to families and society. Surgical treatment plays a dominant role in the treatment of non-advanced esophageal cancer. However, cancer cells in esophageal cancer lesions are highly invasive, postoperative recurrence and metastasis rates are pretty high. More effective systemic and comprehensive treatment is urgently needed to improve the prognosis. We invited 52 doctors in esophageal surgery, oncology, pathology, imaging, and radiation therapy of 32 hospitals at all levels in Henan province, to repeatedly negotiate and fully discuss in combination with evidence and clinical practice experience. Finally, “diagnosis and treatment pathway of neoadjuvant immunotherapy for esophageal cancer in Henan province” was formulated. In this treatment pathway, seven recommendations were proposed from seven perspectives including target population, patient evaluation, protocol selection, surgical timing, postoperative management, organ preservation, and general principles to offer reference for medical personnel related to esophageal cancer surgery.

Ethical Problems and Countermeasures in Rehabilitation Intervention for Patients with lymphedema after Breast Cancer Operation / 中国医学伦理学

In order to explore the medical and social problems related to postoperative lymphedema in breast cancer patients, improve the compliance of rehabilitation treatment and help patients return to society. The self-designed questionnaire was used to investigate 76 patients who met the criteria of lymphedema after breast cancer and refused or failed to adhere to rehabilitation threapy. According to the relevant measurement scale theory and method, the computer-aided software was used to analyze the data to find out the problem and analyze the cause. The prominent problems of poor compliance in patients with breast cancer after operation were successively: subjective factors, objective factors, family social and ethical factors, multidisciplinary factors, hospital management and policy issues. For the above ethical problems, we should adopt positive coping strategies to increase the compliance of patients and improve their quality of life.

Association of attention deficit hyperactivity disorder symptoms and bullying behavior in children / 中国学校卫生

Objective@#The association between school bullying and attention deficit hyperactivity disorder (ADHD) symptoms among students in primary schools and the moderating role of gender was explored to provide scientific evidence for the prevention and control of school bullying.@*Methods@#A total of 4 764 students from 2 primary schools in Wuhan were selected using the convenience sampling method in March 2023. The Olweus Bully/Victim Questionnaire and Strengths and Difficulties Questionnaire were used. A Pearson χ 2 test was used to compare differences in school bullying rates among children with and without ADHD symptoms. Pearson correlation analysis and Process 3.3 were used to analyse the association between ADHD symptoms, and school bullying behaviour and the moderating role of gender.@*Results@#The reported rate of bullying victims in primary schools was 24.2% and the rate of bullying perpetration was 3.8%. The rate of ADHD symptom detection among primary school students was 5.9%. ADHD symptoms were positively associated with bullying and bullying victim behaviour ( r =0.16, 0.27, P <0.01). Specifically, the association between ADHD symptoms and bullying behavior tended to be stronger among boys than girls ( β boy =0.17, t =11.13; β girl =0.07, t =4.11, P <0.01).@*Conclusions@#ADHD symptoms are an important factor influencing school bullying behaviors in students, and gender moderates the association. In the process of preventing and controlling school bullying, ADHD symptoms and gender differences should be emphasized and comprehensive interventions should be implemented.

GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

Simulated weightlessness led to the transformation of glycolipid metabolism in the livers of mice / La antigravedad simulada provocó la transformación del metabolismo de los glicolípidos en el hígado de ratones / Antigravidade simulada levou à transformação do metabolismo de glicolipídios no fígado de camundongos

ABSTRACT Objectives: The effects of weightlessness on the liver were studied using a tail suspension (TS) male mouse model. Methods: The effects of 0-, 2- and 4-week TS (CON, TS2 and TS4 groups) on glycogen and lipid content, as well as on the molecular processes of the synthesis and degradation pathways, were examined. Results: (1) The number of glycogenosomes under ultrastructure and the glycogen content were considerably larger in the TS4 group than in the other two groups. (2) In the TS4 group, glycogen synthase activity remained constant while glycogen phosphorylase activity dropped, indicating that glycogen breakdown was reduced. (3) The livers of the TS2 group had the highest lipid and triglyceride content, indicating lipid buildup in the liver at this time. (4) In the TS2 group, the activities of the fatty acid synthesis-related factors acetyl-CoA carboxylase and fatty acid synthase increased, while hepatic lipase decreased, indicating that lipid synthesis increased, while decomposition decreased. (5) In the TS2 group, the protein expression of glucose transporters 1 and 2 increased. Conclusions: From TS2 weeks to TS4 weeks, the main energy consumption mode in the livers of mice transitioned from glucose metabolism to lipid metabolism as glucose use decreased. Level of evidence II; Comparative prospective study.

RESUMEN Objetivos: Se estudiaron los efectos de la antigravedad en el hígado utilizando un modelo de ratón macho en prueba de suspensión de la cola (TS, tail suspension). Métodos: Se examinaron los efectos de la TS a las 0, 2 y 4 semanas (grupos CON, TS2 y TS4) sobre el contenido de glucógeno y lípidos, así como sobre los procesos moleculares de las vías de síntesis y degradación. Resultados: (1) El número de glucogenosomas ultraestructurales y el contenido de glucógeno fueron expresivamente más altos en el grupo TS4 que en los otros dos grupos. (2) En el grupo TS4, la actividad de la glucógeno sintasa se mantuvo constante, mientras que la actividad de la glucógeno fosforilasa disminuyó, lo que indica que la degradación del glucógeno se redujo. (3) Los hígados del grupo TS2 presentaron el mayor contenido de lípidos y triglicéridos, lo que indica la acumulación de lípidos en el hígado en ese momento. (4) En el grupo TS2, la actividad de los factores relacionados con la síntesis de ácidos grasos acetil-CoA carboxilasa y ácido graso sintasa aumentó, mientras que la lipasa hepática disminuyó, indicando que la síntesis de lípidos aumentó mientras que la descomposición disminuyó. (5) En el grupo TS2, la expresión proteica de los transportadores de glucosa 1 y 2 aumentó. Conclusiones: Desde la semana TS2 hasta la semana TS4, el principal modo de consumo de energía en el hígado de los ratones pasó del metabolismo de la glucosa al metabolismo de los lípidos a medida que disminuía el uso de la glucosa. Nivel de Evidencia II, Estudio retrospectivo comparativo.

RESUMO Objetivos: Os efeitos da antigravidade no fígado foram estudados usando um modelo de camundongo macho com a suspensão pela cauda (TS, tail suspension). Métodos: Foram examinados os efeitos da TS em 0, 2 e 4 semanas (grupos CON, TS2 e TS4) sobre o conteúdo de glicogênio e lipídios, bem como nos processos moleculares das vias de síntese e degradação. Resultados: (1) O número de glicogenossomos ultraestruturais e o teor de glicogênio foram expressivamente maiores no grupo TS4 do que nos outros dois grupos. (2) No grupo TS4, a atividade de glicogênio sintase permaneceu constante, enquanto a atividade de glicogênio fosforilase caiu, indicando que a degradação do glicogênio foi reduzida. (3) Os fígados do grupo TS2 tiveram o maior teor lipídico e de triglicérides, indicando acúmulo de lipídios no fígado no momento. (4) No grupo TS2, a atividade dos fatores relacionados com a síntese de ácidos graxos acetil-CoA carboxilase e ácido graxo sintase aumentaram, enquanto a lipase hepática diminuiu, indicando que a síntese de lipídios aumentou, enquanto a decomposição diminuiu. (5) No grupo TS2, a expressão proteica dos transportadores de glicose 1 e 2 aumentou. Conclusões: De TS2 semanas para TS4 semanas, o principal modo de consumo de energia no fígado de camundongos passou do metabolismo da glicose para o metabolismo lipídico, à medida que o uso de glicose diminuiu. Nível de evidência II, Estudo retrospectivo comparativo.

Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease / 中华儿科杂志

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

Clinical and gene mutation characteristics of patients with hereditary ellipsocytosis: nine cases report and literature review / 中华血液学杂志

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.

Diacylated anthocyanins from purple sweet potato (Ipomoeabatatas L.) attenuate hyperglycemia and hyperuricemia in mice induced by a high-fructose/high-fat diet / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.

Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.@*METHODS@#This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.@*RESULTS@#GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05).@*CONCLUSION@#GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.

Predictive validation of existing bleeding and thromboembolic scores in elderly patients with comorbid atrial fibrillation and acute coronary syndrome / 老年心脏病学杂志（英文版）

BACKGROUND@#The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients.@*METHODS@#A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared.@*RESULTS@#During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar.@*CONCLUSIONS@#The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

MLL4 Regulates the Progression of Non–Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. @*Materials and Methods@#RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis. @*Results@#We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties. @*Conclusion@#Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

Analysis of Related Factors Affecting the Risk Assessment of Death during Hospitalization of Extremely Low Birth Weight Infants / 中山大学学报(医学科学版)

ObjectiveTo explore the influencing factors of different scores on predicting death risk of extremely low birth weight infants （ELBWI）. MethodsA total of 186 cases of ELBWI admitted by the Children's Hospital affiliated to Nanjing Medical University and the Lishui Branch of the Affiliated Zhongda Hospital of Southeast University were admitted from January 1， 2019 to January 1， 2021， and 125 ELBWIs were finally included after screening by inclusion and exclusion criteria. There were 47 cases in the death group and 78 cases in the survival group. General data and the items of score for neonatal acute physiology version Ⅱ （SNAP-Ⅱ）， simplified version of the score for neonatal acute physiology perinatal extension （SNAPPE-Ⅱ）， clinical risk index for babies （CRIB）， clinical risk index for babies Ⅱ （CRIB-Ⅱ） and the national critical illness score （NCIS） were collected. Univariate and multivariate analysis was performed and nomogram was evaluated using receiver operating characteristic curve （ROC）. ResultsIt was found that systolic blood pressure， maximum inhaled oxygen concentration， BE value and birth weight were important factors in ELBWI mortality risk assessment ［systolic blood pressure OR： 0.968， 95%CI： 0.938-0.999， P=0.043； maximum inhaled oxygen concentration OR： 1.020， 95%CI： 1.006-1.034， P=0.006； BE OR： 0.868， 95%CI： 0.786-0.959， P=0.005； birth weight OR： 0.994， 95%CI： 0.991-0.997， P=0.000］. ROC showed that the area under the curve of the above four variables is 0.71， and the 95% confidence interval is 0.610-0.799， which is better than CRIB score. ConclusionLower systolic blood pressure， higher inhaled oxygen concentration， higher BE and lower birthweight are important influencing factors to predict the death risk of ELBWI. The above four items should be included in the newly developed score assessment to obtain a more effective ELBWI prediction system.

Prevalence and influencing factors of elevated blood pressure among primary and middle school students in Anhui Province / 中国学校卫生

Objective@#To analyze the prevalence of elevated blood pressure among primary and middle school students in Anhui Province in 2022, as well as its influencing factors, so as to provide scientific evidence for the development of effective measures to prevent and control elevated blood pressure among children and adolescents.@*Methods@#Using data from the 2022 "Monitoring of Common Diseases and health Influencing Factors of Students" in Anhui Province, a total of 210 360 primary and middle school students aged 7 to 17 with complete information. Statistical analysis, including independent sample t tests, analysis of variance, and Chi square tests, were conducted to compare blood pressure differences and prevalence rates among students with different characteristics. Generalized linear mixed models were established to analyze the influencing factors of elevated blood pressure in children and adolescents.@*Results@#The overall prevalence of elevated blood pressure among primary and middle school students in Anhui Province was 22.3%, higher among high school students (25.6%) and junior high school students ( 23.7%) than elementary school students (20.4%) ( χ 2=528.49, P < 0.01 ); higher among obese(33.3%) and overweight students (24.9%) than that of normal students (18.6%) ( χ 2=3 704.52, P <0.01), higher among rural students (23.1%) than urban students (21.4%) ( χ 2=83.39, P <0.01), and higher in the northern part of Anhui Province (26.9%) than in the central part (21.9%) and southern part (17.6%) ( χ 2=1 777.51, P <0.01). The generalized linear mixed models revealed that girls, high school stage, overweight, obese, living in the northern part of Anhui Province, and living in rural were all positively correlated with elevated blood pressure( OR =1.11，1.25，1.47，1.45，2.24，1.21，1.67， P <0.01).@*Conclusions@#The prevalence of elevated blood pressure among children and adolescents in Anhui Province is the highest in the country. It is recommended that relevant departments promptly formulate corresponding measures to curb the increasing trend of elevated blood pressure and protect the physical and mental health of children and adolescents.