FYB1-targeted modulation of CAPG promotes AML progression.

Acute myeloid leukemia (AML) is a rare and heterogeneous disease. Over the past few decades, patient prognosis has improved with continuous improvements in treatment, but outcomes for some patients with primary drug resistance or relapse after treatment remain poor. Additional therapies to improve outcomes for these patients are urgently needed. FYB1 expression differs substantially between AML tissues and normal tissues. High FYB1 expression is correlated with poorer overall survival (OS), indicating that FYB1 may regulate AML progression. Therefore, understanding the effect of FYB1 on AML could improve the success rate of therapeutic approaches and prognosis for patients with AML. In this study, through analysis of large databases and both in vivo and in vitro experiments, we assessed the expression and role of FYB1 in AML and the relationship of FYB with patient prognosis. Downstream targets of the FYB1 gene were analyzed by RNA-seq. Database mining and in vitro experiments were used to further clarify the effect of the downstream target gelsolin-like actin-capping protein (CAPG) on AML cells and its relationship with patient prognosis. FYB1 expression was significantly higher in AML tissue and corresponded with a poor prognosis. FYB1 knockdown inhibited AML cell proliferation, promoted cell apoptosis, reduced cell adhesion capability and significantly reduced the tumor formation rate in mice. In addition, FYB1 knockdown induced a notable decrease in CAPG expression. The suppression of CAPG significantly inhibited cell proliferation and increased cell apoptosis. The conclusions of this study underscore the pivotal role of the FYB1/CAPG axis in promoting AML. We propose that the FYB1/CAPG axis could serve as a new thread in the development of therapeutic strategies for AML.

Nanobubble water promotes anaerobic digestion of high-solids cattle manure under mesophilic and thermophilic conditions.

The gradual increase in cattle farming has led to a huge production of cattle manure (CM), but the conventional treatment methods are less efficient. In this study, the treatment method of anaerobic digestion (AD) of high-solids CM by combining nanobubble water (NBW) with different gases was proposed to present a new idea for the reduction, harmlessness, and resourcefulness of CM. It was found that the performance of the digester with added NBW was better than the control. Among them, the cumulative methane yield T-Air: 227.09 mL g-1 VSadded and T-CO2: 226.12 mL g-1 VSadded increased by 17.72 % and 17.22 %, respectively, compared with the control T: 192.90 mL g-1 VSadded under thermophilic conditions. Under mesophilic conditions, M-Air: 162.39 mL g-1 VSadded increased by 9.68 % compared with control M: 148.05 mL g-1 VSadded. Microbial communities analyzed at the genus level revealed that the relative abundance of bacteria favorable to hydrolysis and acid-producing processes, such as Defluviitalea, Haloplasma, and Bacillus, increased to varying degrees. Moreover, the relative abundance of archaea favorable for methanogenesis, such as Methanoculleus, Methanobrevibacter, and Methanosarcina, also increased to varying degrees. Therefore, the addition of NBW promoted the hydrolysis of high-solids CM, enhanced the stability of the reaction, improved the methanogenic performance, and increased the RA of favorable genera, which ultimately led to a better performance of the AD of high-solids CM.

Mycobacterium abscessus pulmonary disease presenting with spontaneous pneumomediastinum and subcutaneous emphysema in childhood acute lymphoblastic leukemia: a case report and literature review.

INTRODUCTION: Mycobacterium abscessus is a rapidly growing mycobacterium commonly identified in adults with underlying pulmonary diseases but is rarely observed in children. A better understanding of this pathogen in children is essential. CASE PRESENTATION: We report the case of a 49-month-old female child without previous underlying pulmonary diseases but with acute lymphoblastic leukemia (ALL). The patient was complicated with pneumonia during chemotherapy, which was primarily characterized by spontaneous pneumomediastinum and subcutaneous emphysema on chest computed tomography (CT). M. abscessus sequences were detected by metagenomic next-generation sequencing in bronchoalveolar lavage fluid. With mechanical ventilation, closed thoracic drainage, and anti-infective therapy for 6 months, the patient's infection was controlled. The patient completed 2.5 years of treatment for ALL, and the drugs were discontinued. The patient currently remains in complete hematologic remission. DISCUSSION: We reviewed the literature on 33 children with M. abscessus pulmonary disease. These children mostly had underlying immunodeficiency. Chest CT most often showed nodular shadows, consolidation, and bronchiectasis. Spontaneous pneumomediastinum and subcutaneous emphysema were not reported as major manifestations. CONCLUSION: Spontaneous pneumomediastinum and subcutaneous emphysema were our patient's main characteristics on chest CT, and this study enriches the knowledge regarding possible imaging changes in M. abscessus pulmonary disease in children. This case report reflects good clinical experience in maintaining the balance between chemotherapy and anti-infective therapy in childhood ALL.

A multi-center clinical investigation on invasive Streptococcus pyogenes infection in China, 2010-2017.

BACKGROUND: Invasive S. pyogenes diseases are uncommon, serious infections with high case fatality rates (CFR). There are few publications on this subject in the field of pediatrics. This study aimed at characterizing clinical and laboratory aspects of this disease in Chinese children. PATIENTS AND METHODS: A retrospective study was conducted and pediatric in-patients with S. pyogenes infection identified by cultures from normally sterile sites were included, who were diagnosed and treated in 9 tertiary hospitals during 2010-2017. RESULTS: A total of 66 cases were identified, in which 37 (56.1%) were male. The median age of these patients, including 11 neonates, was 3.0 y. Fifty-nine (89.4%) isolates were determined from blood. Fever was the major symptom (60/66, 90.9%) and sepsis was the most frequent presentation (64/66, 97.0%, including 42.4% with skin or soft tissue infections and 25.8% with pneumonia. The mean duration of the chief complaint was (3.8 ± 3.2) d. Only 18 (27.3%) patients had been given antibiotics prior to the hospitalization. Among all patients, 15 (22.7%) developed streptococcal toxin shock syndrome (STSS). No S. pyogenes strain was resistant to penicillin, ceftriaxone, or vancomycin, while 88.9% (56/63) and 81.4% (48/59) of the tested isolates were resistant to clindamycin and erythromycin respectively. Most of the patients were treated with ß-lactams antibiotics and 36.4% had been treated with meropenem or imipenem. Thirteen (19.7%) cases died from infection, in which 9 (13.6%) had complication with STSS. CONCLUSIONS: Invasive S. pyogenes infections often developed from skin or soft tissue infection and STSS was the main cause of death in Chinese children. Ongoing surveillance is required to gain a greater understanding of this disease.

Treatment outcome of young children with acute lymphoblastic leukaemia: achievements and directions implied from Shanghai Children's Medical Centre based SCMC-ALL-2005 protocol.

This multicenter study used the Shanghai Children's Medical Center (SCMC)-ALL-2005 protocol for treatment of young patients (<2 years old) with acute lymphoblastic leukaemia (ALL), which was designed to improve treatment outcome in Chinese paediatric patients. These aims were pursued through risk-directed stratification based on presenting clinical and genetic features, minimal residual disease (MRD) levels and treatment response. All the patients achieved completed remission with 5-year event-free survivals of 82·6 ± 9·7% (low risk), 52·6 ± 8·4% (intermediate risk), 28·6 ± 17·1% (high risk). Disease recurrence was detected in bone marrow, bone marrow plus testis, testis alone and central nervous system in 16 (24·2%), 1 (1·5%), 1 (1·5%) and 1 (1·5%) patients respectively. No deaths were reported during induction. The SCMC-ALL-2005 trial for ALL patients <2 years old indicated high remission induction and low infection and treatment-related mortality rates.

Endoscopic Arthroplasty via Mini-open Direct Anterior Approach Improves Postoperative Complications and Acetabular Components of Total Hip Arthroplasty in Obese Patients.

To overcome the high-risk complications and poor alignment of acetabular components in obese patients associated with direct anterior approach (DAA) for total hip arthroplasty (THA), we innovated an endoscopic arthroplasty via mini-open direct anterior approach technique (Endo-DAA). The purpose of this study was to compare the clinical and radiographic outcomes in obese patients subjected to THA between Endo-DAA, Bikini DAA, and conventional DAA. In this retrospective controlled study, a total of 360 consecutive primary THA on obese patients (body mass index greater than 28 kg/m2) via Endo-DAA, Bikini DAA, and conventional DAA performed from October 2017 to October 2022 by different surgeons and in a single center were included. Assessments including perioperative parameters, clinical outcomes, complications, and radiologic measurements were retrieved from patients before the surgery, perioperative period and the latest follow-up. A total of 360 consecutive THA (Endo-DAA = 108, Bikini DAA = 116, Conventional DAA = 136) with complete follow-up data were analyzed. Compared to Bikini DAA or conventional DAA, Endo-DAA significantly shortened the length of incision (5.46 ± 0.53), the duration of operation (64.47 ± 12.38), and postoperative hospital stay (2.15 ± 0.89). Endo-DAA significantly reduces wound related complications compared with conventional DAA. Besides, Endo-DAA achieved a significantly better alignment of acetabular components compared to Bikini DAA or conventional DAA. Furthermore, Endo-DAA improved postoperative pain at the activity at 24 h postoperatively and early functional scores. The Endo-DAA THA technique provides better short-term clinical and radiographic results in obese patients with a low rate of postoperative complications compared to Bikini DAA or conventional DAA.

Effects of milk-derived bioactive peptide VPP on diarrhea of pre-weaning calves.

A well-known milk-derived bioactive tripeptide, VPP (Val-Pro-Pro) has good anti-inflammatory, anti-hypertension, and anti-hydrolysis properties. However, whether VPP can alleviate calf intestinal inflammation is unclear. In this experiment, the effects of VPP on growth, diarrhea incidence, serum biochemical indices, short-chain fatty acids, and fecal microorganisms were examined in pre-weaning Holstein calves. Eighteen calves with similar birth date, body weight, and genetic background were randomly assigned equally to two groups (n = 9). The control group was given 50 mL of phosphate buffer saline before morning feeding, whereas the VPP group received 50 mL of VPP solution (100 mg/kg body weight/d). The study lasted for 17 days, with the first 3 days used for adaptation. Initial and final body weights were determined, and daily dry matter intake and fecal score were recorded throughout the study. Serum hormone levels and antioxidant and immune indices were measured on day 14. Fecal microorganisms were collected on days 0, 7, and 14, and 16S rDNA sequencing was performed. Oral administration of VPP did not significantly affect calf average daily feed intake and body weight, but the growth rate in body weight was significantly higher in the VPP group than in the control group on day 7 (P < 0.05). Compared with the control, VPP significantly decreased serum TNF-α and IL-6 contents (P < 0.05), and concentrations of nitric oxide and IL-1ß also decreased but not significantly (0.05 < P < 0.1). After seven days of VPP, relative abundances of g_Lachnoclostridium, uncultured_bacterium_, and g_Streptococcus in fecal samples increased significantly (P < 0.05). Compared with the control, VPP significantly increased concentrations of the fecal short-chain fatty acids n-butyric acid and isovaleric acid (P < 0.05). In conclusion, VPP can relieve intestinal inflammation and alleviate the degree of diarrhea in pre-weaning calves.

Comparative study of posaconazole and voriconazole for primary antifungal prophylaxis in patients with pediatric acute leukemia.

Posaconazole and voriconazole are commonly used for preventing invasive fungal disease (IFD), but few studies compared posaconazole with voriconazole for primary antifungal prophylaxis (PAP) in pediatric acute leukemia. To compare posaconazole with voriconazole for PAP in pediatric acute leukemia. This retrospective observational study enrolled pediatric patients with non-M3 acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) between December 2017 and November 2019 in the Second Affiliated Hospital of Anhui Medical University. The patients received voriconazole or posaconazole for PAP. The primary outcome was the breakthrough of IFD. The secondary outcome was the overall survival (OS) and IFD-free survival of patients. A total of the 275 patients were enrolled, of which 120 patients taking voriconazole (43.6%) and 155 patients taking posaconazole (56.4%). The breakthrough of IFD occurred in 19 (15.8%) patients taking voriconazole and in 12 (7.7%) patients taking posaconazole (P = 0.035). There was no significant differences in IFD-free survival (P = 0.336) or OS (P = 0.069) between the patients taking voriconazole and posaconazole. In the subgroup of AML patients, the OS of patients taking posaconazole was better than those receiving voriconazole (P = 0.017). Posaconazole and voriconazole were comparable for PAP in patients with pediatric acute leukemia regarding the OS and IFD-free survival, but posaconazole might achieve a lower IFD breakthrough rate.

Colonization and development of the gut microbiome in calves.

Colonization and development of the gut microbiome are crucial for the growth and health of calves. In this review, we summarized the colonization, beneficial nutrition, immune function of gut microbiota, function of the gut barrier, and the evolution of core microbiota in the gut of calves of different ages. Homeostasis of gut microbiome is beneficial for nutritional and immune system development of calves. Disruption of the gut microbiome leads to digestive diseases in calves, such as diarrhea and intestinal inflammation. Microbiota already exists in the gut of calf fetuses, and the colonization of microbiota continues to change dynamically under the influence of various factors, which include probiotics, diet, age, and genotype. Colonization depends on the interaction between the gut microbiota and the immune system of calves. The abundance and diversity of these commensal microbiota stabilize and play a critical role in the health of calves.

Modulating gastrointestinal microbiota to alleviate diarrhea in calves.

The calf stage is a critical period for the development of heifers. Newborn calves have low gastrointestinal barrier function and immunity before weaning, making them highly susceptible to infection by various intestinal pathogens. Diarrhea in calves poses a significant threat to the health of young ruminants and may cause serious economic losses to livestock farms. Antibiotics are commonly used to treat diarrhea and promote calf growth, leading to bacterial resistance and increasing antibiotic residues in meat. Therefore, finding new technologies to improve the diarrhea of newborn calves is a challenge for livestock production and public health. The operation of the gut microbiota in the early stages after birth is crucial for optimizing immune function and body growth. Microbiota colonization of newborn animals is crucial for healthy development. Early intervention of the calf gastrointestinal microbiota, such as oral probiotics, fecal microbiota transplantation and rumen microbiota transplantation can effectively relieve calf diarrhea. This review focuses on the role and mechanisms of oral probiotics such as Lactobacillus, Bifidobacterium and Faecalibacterium in relieving calf diarrhea. The aim is to develop appropriate antibiotic alternatives to improve calf health in a sustainable and responsible manner, while addressing public health issues related to the use of antibiotics in livestock.

Comparison of Thermophilic-Mesophilic and Mesophilic-Thermophilic Two-Phase High-Solid Sludge Anaerobic Digestion at Different Inoculation Proportions: Digestion Performance and Microbial Diversity.

This study investigated the performance of thermophilic-mesophilic (T-M) and mesophilic-thermophilic (M-T) two-phase sludge anaerobic digestion at different inoculation proportions after a change in digestion temperature. After temperature change, the pH, total ammonia nitrogen (TAN), free ammonia nitrogen (FAN), solubility chemical oxygen demand (SCOD), and total alkalinity (TA) levels of two-phase digesters were between thermophilic control digesters and mesophilic control digesters. However, the volatile fatty acid (VFA) levels of two-phase digesters were higher than those of thermophilic or mesophilic control digesters. The bacteria communities of M-T two-phase digesters were more diverse than those of T-M. After a change in digestion temperature, the bacterial community was dominated by Coprothermobacter. After a change of digestion temperature, the relative abundance (RA) of Methanobacterium, Methanosaeta, and Methanospirillum of M-T two-phase digesters was higher than that of T-M two-phase digesters. In comparison, the RA of Methanosarcina of T-M two-phase digesters was higher than that of M-T two-phase digesters. The ultimate methane yields of thermophilic control digesters were greater than those of mesophilic control digesters. Nevertheless, the ultimate methane yield levels of M-T two-phase digesters were greater than those of T-M two-phase digesters. The ultimate methane yields of all two-phase digesters presented an earlier increase and later decrease trend with the increasing inoculation proportion. Optimal methane production condition was achieved when 15% of sludge (T-M15) was inoculated under mesophilic-thermophilic conditions, which promoted 123.6% (based on mesophilic control) or 27.4% (based on thermophilic control). An optimal inoculation proportion (about 15%) balanced the number and activity of methanogens of high-solid sludge anaerobic digestion.

Prolonged use of eltrombopag in patients with severe aplastic anemia in the real world.

Eltrombopag (EPAG) can improve the efficacy of immunosuppressive therapy (IST) consisting of antithymocyte immunoglobulin (ATG) and cyclosporin in severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous usage of EPAG beyond 6 months.Seventy-four treatment-naive Chinese patients with SAA were administrated with rabbit ATG-based IST plus EPAG for 6 months. Patients not achieving complete remission (CR) at 6 months were treated with EPAG for another 6 months.At 1, 3, 6 and 12 months after IST, the cumulative response rates were 31%, 61%, 82% and 90%, and the cumulative CR rates were 0, 14%, 27% and 45%, respectively. The cumulative effect curve showed that 93% and 53% of all remission and CR occurred within 6 months, while 98% and 83% of all remission and CR occurred within 12 months. Thirty-seven percent of patients (11 of 30) with partial remission (PR) at 6 months continuously exposed to EPAG improved to CR within 3 (1-5) months of the extended median time. Six patients failing at 6 months continued to use EPAG. Three patients showed improved responses with an extended median time of 6 (1-6) months. The 2-year event-free survival (EFS) was better in those continuing with EPAG (89% vs. 49%, P = 0.006) for patients with PR or non-remission at 6 months.Continuous administration with EPAG could improve the hematologic response and EFS in patients without achieving CR at 6 months.This trial has been registered at the Chinese Clinical Trial Registry (ChiCTR2100045895).

The Influence of Occupational Therapy on College Students' Home Physical Exercise Behavior and Mental Health Status under the Artificial Intelligence Technology.

The core of occupational therapy is to help patients with mental illness recover their social work, give play to their self-worth, obtain financial resources, and improve their self-confidence. Occupational therapy can help patients relieve symptoms and restore social function, reduce disease recurrence, and improve the reemployment rate and the overall health level of patients. In order to deeply excavate the inner connection between the mental health status and physical exercise status of college students, the physical exercise behavior of college students during home isolation is studied. First, the "physical exercise behavior questionnaire" and "symptom self-assessment scale" were used to investigate the physical exercise behavior and mental health status of college students. Second, descriptive statistics, correlation analysis, independent sample t-test, and variance analysis were carried out on the survey results using mathematical statistics methods and big data technology. The survey results show high reliability, and the Cronbach's α coefficients were all greater than 0.9. There was a positive correlation between physical exercise methods and mental health in general, and the difference in the degree of exercise is significantly different from the mental health of students (p < 0.05). With the increase of exercise intensity, the score of "symptom self-assessment scale" first decreased and then increased, and the exercise intensity of medium and high intensity showed the best psychological state. And the correlation dimension of depression was the highest. This indicated that the students who liked family physical exercise were less likely to suffer from depression. In addition, depression was the most relevant dimension with self demand physical exercise, and interpersonal sensitivity was the most relevant dimension with social expansion physical exercise. The conclusion shows that the more active the students participate in family physical exercise, the healthier their mental state is. Occupational therapy has obvious curative effect on depression, which can improve patients' negative symptoms, their living ability, and social function. Meanwhile, analyzing data through big data technology reduces human workload and improves data processing efficiency and accuracy. The scheme proposed here provides some ideas for the application of big data technology in occupational therapy.

Research progress on the application of optical coherence tomography in the field of oncology.

Optical coherence tomography (OCT) is a non-invasive imaging technique which has become the "gold standard" for diagnosis in the field of ophthalmology. However, in contrast to the eye, nontransparent tissues exhibit a high degree of optical scattering and absorption, resulting in a limited OCT imaging depth. And the progress made in the past decade in OCT technology have made it possible to image nontransparent tissues with high spatial resolution at large (up to 2mm) imaging depth. On the one hand, OCT can be used in a rapid, noninvasive way to detect diseased tissues, organs, blood vessels or glands. On the other hand, it can also identify the optical characteristics of suspicious parts in the early stage of the disease, which is of great significance for the early diagnosis of tumor diseases. Furthermore, OCT imaging has been explored for imaging tumor cells and their dynamics, and for the monitoring of tumor responses to treatments. This review summarizes the recent advances in the OCT area, which application in oncological diagnosis and treatment in different types: (1) superficial tumors:OCT could detect microscopic information on the skin's surface at high resolution and has been demonstrated to help diagnose common skin cancers; (2) gastrointestinal tumors: OCT can be integrated into small probes and catheters to image the structure of the stomach wall, enabling the diagnosis and differentiation of gastrointestinal tumors and inflammation; (3) deep tumors: with the rapid development of OCT imaging technology, it has shown great potential in the diagnosis of deep tumors such in brain tumors, breast cancer, bladder cancer, and lung cancer.

Whole transcriptome sequencing reveals a TCF4-ZNF384 fusion in acute lymphoblastic leukemia.

Previous studies have shown that, the clinical features and prognosis of ZNF384-rearranged pediatric acute lymphoblastic leukemia (ALL) depend on its translocation partners. We report two cases of TCF4-ZNF384 fusion, one 6-year-old girl and one 10-year-old boy, both diagnosed by whole-transcriptome sequencing, and TCF4 is the newest fusion partner of ZNF384. As illustrated in this first report of TCF4-ZNF384 fusion in ALL patients, the identification of patients with ZNF384 rearrangement in ALL patients is critical to elucidate outcomes associated with a specific rearrangement and to develop appropriate treatment strategies. In addition, the development of other methods to detect ZNF384 specific translocation partners and leukemia specific targeting agents is of great significance to further improve the prognosis of ALL with ZNF384-rearrangement.

[Single Center Clinical Analysis of Bloodstream Infection Pathogens in Children with Acute Leukemia].

OBJECTIVE: To investigate the clinical features, distribution of pathogenic bacteria, and drug resistance of bloodstream infection in children with acute leukemia. METHODS: Clinical data of 93 blood culture-positive children with acute leukemia from January 2015 to December 2019 in Department of Pediatrics, The Second Hospital of Anhui Medical University were analyzed retrospectively. RESULTS: In these 93 cases, 78 cases were in the period of neutrophil deficiency. There were 54 Gram-negative bacteria (G-) (58.1%) found through blood culture, and the top 4 strains were Escherichia coli (15.1%), Klebsiella pneumoniae (13.9%), Pseudomonas aeruginosa (6.5%), and Enterobacter cloacae (6.5%). There were 39 Gram-positive bacteria (G+) (41.9%) detected, and the top 4 strains were Staphylococcus epidermidis (10.8%), Streptococcus pneumoniae (6.5%), Staphylococcus hemolyticus (5.4%), and Staphylococcus human (5.4%). Among 74 strains of pathogenic bacteria from acute lymphoblastic leukemia (ALL) children, there were 29 strains of G+ bacteria (39.2%) and 45 strains of G- bacteria (60.8%). While in 19 strains from acute myeloblastic leukemia (AML) patients, G- bacteria accounted for 47.4% and G+ bacteria accounted for 52.6%. In 15 ALL children without neutropenia, G+ bacteria made up the majority of the strains (66.7%). In the 93 strains of pathogenic bacteria, 13 (13.9%) strains were multidrug-resistant. Among them, extended-spectrum ß-lactamases accounted for 42.9%, carbapenemase-resistant enzyme Klebsiella pneumoniae 15.4%, and carbapenemase-resistant enzyme Enterobacter cloacae strains 33.3%, which were detected from G- bacteria. While, 13.3% of methicillin-resistant coagulase-negative Staphylococci accounted for 13.3% detected from G+ bacteria, but linezolid, vancomycin, teicoplanin Staphylococcus and Enterococcus resistant were not found. The average procalcitonin (PCT) value of G- bacteria infection was (11.02±20.282) ng/ml, while in G+ infection it was (1.81±4.911) ng/ml, the difference was statistically significant (P<0.05). The mean value of C-reactive protein (CRP) in G- infection was (76.33±69.946) mg/L, and that in G+ infection was (38.34±57.951) mg/L. The prognosis of active treatment was good, and only one case died of septic shock complicated with disseminated intravascular coagulation (DIC) and gastrointestinal bleeding caused by carbapenemase-resistant enzyme enterobacteriaceae. CONCLUSION: G- is the major bacteria in acute leukemia children with bloodstream infection, but the distribution of ALL and AML strains is different. G- bacteria dominates in ALL, while G+ bacteria and G- bacteria are equally distributed in AML. Non-agranulocytosis accompanied by bloodstream infections is dominant by G+ bacteria. The mean value of PCT and CRP are significantly higher in G- bacteria infection than in G+ bacteria.

Selective antitumor activity of drug-free TPGS nanomicelles with ROS-induced mitochondrial cell death.

D-a-tocopheryl polyethylene glycol succinate (TPGS) as a FDA-approved safe adjuvant has shown an excellent application in the targeting delivery of antitumor drugs and overcoming multidrug resistance. Beside, TPGS can result in apoptogenic activity toward many tumor types because it can induce mitochondrial dysfunction. Therefore, TPGS can serve as an antineoplastic agent. However, the current research on the selective antitumor activity of TPGS is ignored. To reveal the issue, herein we develop a mitochondria-targeting drug-free TPGS nanomicelles with the hydrodynamic diameter of about 100 nm and outstanding serum stability by weak interaction-driven self-assembly of the amphiphilic TPGS polymer. Moreover, such drug-free TPGS nanomicelles intravenously injected into tumor-bearing mice exhibit long blood circulation time, superior tumor enrichment, and inhibit the tumor growth via inducing excessive reactive oxygen species (ROS) generation within tumor cells. Further in vitro and in vivo researches jointly demonstrate that drug-free TPGS nanomicelles have more significant antitumor effect on HeLa cells compared with that of other tumor cells. On the contrary, drug-free TPGS nanomicelles display the low toxicity toward normal cells and tissues. Taken together, these new findings confirm that TPGS drug-free nanomicelles represent simple, multifunctional, safe, and efficient antineoplastic agents, which can be expected to bring new light on the development of drug-free polymers for tumor therapy.

[Influencing Factors in the Chronicity of Immune Thrombocytopenia in Children].

OBJECTIVE: To explore the influencing factors in children with chronicity immune thrombocytopenia (ITP), and to provide basis for judging the prognosis and treatment in children with ITP. METHODS: The clinical data of children with ITP admitted to The Second Affiliated Hospital of Anhui Medical University in the past 5 years were retrospectively analyzed and followed up for more than 1 year. According to the inclusion criteria, the eligible cases (328 cases in total) were selected and collected through medical record system retrieval, outpatient clinic and telephone follow-up. Independent influencing factors affecting the prognosis of children with ITP were obtained through single-factor and multi-factor logistic analysis, and their predictive value for the prognosis of ITP in children were evaluated. RESULTS: Of 328 children with ITP, 208 were newly diagnosed with ITP (64%), 54 were persistent ITP (16%), 66 were chronic ITP (20%), and the remission rate within 1 year was 79.9%. The results of univariate analysis showed that, age, pre-morbidity history of infection and vaccination, antinuclear antibodies, initial absolute lymphocyte count（ALC） and treatment options were related to the prognosis of the children (P<0.05). Multivariate analysis showed that the history of infection and vaccination before onset, initial treatment options, and ALC at the time of initial diagnosis were independent factors affecting the prognosis of children with ITP (P<0.05). The time for platelet recovery to 100×109/L in the initial treatment group combined with intravenous immunoglobulin (IVIG) was shorter than that in the single corticosteroids group (P<0.01). The receivers operating characteristic (ROC) was drawn with the development of chronic disease (course >12 months) as state variable and ALC or ALC combined with preceding infection or vaccination history as test variable. The results showed that when the absolute value of lymphocytes was 3.80×109/L, the area under the curve was the largest (0.787), the sensitivity was 80.6%, and the specificity was 65.53% (P<0.01), the combined results showed that the maximum area under the curve was 0.859, the sensitivity was 77.61%, and the specificity was 78.41%. CONCLUSION: The initial treatment plan combined with IVIG can reduce the occurrence of chronicity in children with ITP, and its efficacy is better than that of the single corticosteroids group (the platelet recovery time is shorter); history of preceding infection or vaccination, ALC at the time of initial diagnosis are independent factors affecting the prognosis of children with ITP, and the combination of the two shows a better predictive value for the prognosis.

Long-term follow-up of acute lymphoblastic leukemia in young children treated by the SCMC-ALL-2009 protocol.

This study evaluated the long-term therapeutic effect and prognostic factors of acute lymphoblastic leukemia (ALL) in 100 young Chinese children (<2 years old) who were enrolled in the Shanghai Children's Medical Center (SCMC)-ALL-2009 study in five pediatric hematological disease centers based on collaboration. The 5-year and 10-year event-free survivals (EFS) were 74.7 ± 3.2% and 73.3 ± 3.4%. The 10-year EFS rates for low risk, intermediate-risk, and high-risk patients were 81.9 ± 5.0%, 71.3 ± 4.3%, and 22.2 ± 13.9%, respectively. Relapse occurred in 19 patients. MRD results on day 55, good or poor response to prednisolone, and age at diagnosis were shown to have important prognostic and therapeutic implications. Compared with the SCMC-ALL-2005 protocol, showed that the 10-year-EFS and 10-year-overall survival of the SCMC-ALL-2009 protocol were better than that of the -2005 protocol. Notably, the intermediate-risk group was improved after the chemotherapy intensity was strengthened.

[Relationship between Nutritional Status and Nosocomial Infection in Children with Acute Lymphoblastic Leukemia].

OBJECTIVE: To study the risk factors and infection characteristics of nosocomial infection in children with acute lymphoblastic leukemia (ALL) and analyze the relationship between different nutritional status and nosocomial infection, early treatment response. METHOD: The clinical data of 133 children with ALL treated with CCCG-ALL-2015 from June 2016 to June 2019 (chemotherapy stage, risk level, MRD), infection during hospitalization (course of infection, laboratory indicators, sites of infection, outcome) and nutritional status (sex, age, height/ length, weight) were enrolled. The Chi 2 test and Logistic regression analysis were used for statistical analysis. RESULTS: The rate of nosocomial infection was 19.9% in 133 children with ALL, in which 3 were infection-related death. Sex, immunophenotype and risk showed no significantly affect on the occurrence of nosocomial infection (P＞0.05), but neutrophil count, hemoglobin level, platelet count, chemotherapy stage, length of stay in hospital and nutritional status showed affect on the occurrence of nosocomial infection (P＜0.05). Logistic multivariate regression analysis showed that chemotherapy stage, length of hospital stay, neutrophils and nutritional status were the independent risk factors, in which the respiratory tract infection was the most common. Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 44.1%, 52.9% and 2.9% respectively. The negative rate of MRD in day 19 and day 46 between different nutritional status groups showed statistically significant (P＜0.05). CONCLUSION: Neutrophil count, chemotherapy stage, length of stay in hospital and nutritional status are independent risk factors for nosocomial infection. Among of them, nutritional status negatively correlated with nosocomial infection, and the poorer nutritional status, the higher risk of nosocomial infection. Malnutrition, overweight and obesity can affect the early treatment response of ALL children. The level of nutrition at first diagnosis can be used as a bad factor to evaluate the early treatment response of ALL children.