Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction.

A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbable mutations required for bnAb affinity maturation remains difficult. Here, we demonstrate a process for designing boosting immunogens for a V3-glycan bnAb B cell lineage. The immunogens induced affinity-matured antibodies by selecting for functional improbable mutations in bnAb precursor knockin mice. Moreover, we show similar success in prime and boosting with nucleoside-modified mRNA-encoded HIV-1 envelope trimer immunogens, with improved selection by mRNA immunogens of improbable mutations required for bnAb binding to key envelope glycans. These results demonstrate the ability of both protein and mRNA prime-boost immunogens for selection of rare B cell lineage intermediates with neutralizing breadth after bnAb precursor expansion, a key proof of concept and milestone toward development of an HIV-1 vaccine.

Efficacy and Toxicity of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy in Patients with Unresectable Stage III Non-Small Cell Lung Cancer Receiving Concurrent Chemotherapy: A Multicenter, Randomized Phase 3 Trial.

PURPOSE: The standard treatment schedule for unresectable stage III non-small cell lung cancer (NSCLC) is chemotherapy with concurrent radiation therapy (60 Gy delivered in 30 fractions), although moderately hypofractionated radiation therapy (Hypo-RT) has also been considered as an alternative strategy. This study aimed to compare the efficacy and toxicity of moderately Hypo-RT with helical TomoTherapy versus conventionally fractionated radiation therapy (Con-RT) in patients with unresectable stage III NSCLC receiving concurrent chemotherapy. METHODS AND MATERIALS: In this randomized, multicenter, nonblinded phase 3 clinical trial, eligible patients were randomised at a 1:1 ratio to either the Hypo-RT group (60 Gy in 20 fractions) or Con-RT group (60 Gy in 30 fractions). All patients received 2 cycles of concurrent platinum-based chemotherapy plus 2 cycles of consolidation therapy. The primary endpoint was 3-year overall survival (OS) in the intention-to-treat population. The secondary endpoints were progression-free survival and treatment-related adverse events. RESULTS: A total of 146 patients were enrolled from July 27, 2018, to November 1, 2021. The median follow-up was 46 months. The 3-year OS rates in the Hypo-RT and Con-RT groups were 58.4% and 38.4%, respectively (P = .02). The median OS from randomisation was 41 months in the Hypo-RT group and 30 months in the Con-RT group (hazard ratio, 0.61; 95% confidence interval, 0.40-0.94; P = .02). There was no significant difference in the rates of grade ≥2 treatment-related adverse events between the 2 groups. CONCLUSIONS: Moderately Hypo-RT using helical TomoTherapy may improve OS in patients with unresectable stage III NSCLC, while maintaining toxicity rates.

[Risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus]. / æœ‰è¡€æµåŠ¨åŠ›å­¦æ„ä¹‰çš„åŠ¨è„‰å¯¼ç®¡æœªé—­æ—©äº§å„¿å¸ƒæ´›èŠ¬æ²»ç–—å¤±è´¥çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). METHODS: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis. RESULTS: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% (P<0.05). CONCLUSIONS: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

Eldecalcitol protected osteocytes against ferroptosis of D-gal-induced senescent MLO-Y4 cells and ovariectomized mice.

BACKGROUND: Active vitamin D analog eldecalcitol is clinically applied in treatment of postmenopausal osteoporosis. This study aims to determine the role of eldecalcitol in the protection of osteocytes from senescence and the associated ferroptosis. METHODS: The MLO-Y4 osteocytes were exposed to D-gal inducing senescence. The ovariectomized (OVX) mice treated with D-gal using as an aging inducer were intraperitoneally injected with eldecalcitol. The multiplexed confocal imaging, fluorescence in situ hybridization and transmission electron microscopy were applied in assessing osteocytic properties. Immunochemical staining and immunoblotting were carried out to detect abundance and expression of molecules. RESULTS: The ablation of vitamin D receptor led to a reduction in amounts of osteocytes, a loss of dendrites, an increase in mRNA expression of SASP factors and in protein expression of senescent factors, as well as changes in mRNA expression of ferroptosis-related genes (PTGS2 & RGS4). Eldecalcitol reversed senescent phenotypes of MLO-Y4 cells shown by improving cell morphology and density, decreasing ß-gal-positive cell accumulation, and down-regulating protein expression (P16, P21 & P53). Eldecalcitol reduced intracellular ROS and MDA productions, elevated JC-1 aggregates, and up-regulated expression of Nrf2 and GPX4. Eldecalcitol exhibited osteopreserve effects in D-gal-induced aging OVX mice. The confocal imaging displayed its improvement on osteocytic network organization. Eldecalcitol decreased the numbers of senescent osteocytes at tibial diaphysis by SADS assay and attenuated mRNA expression of SASP factors as well as down-regulated protein expression of senescence-related factors and restored levels of ferroptotic biomarkers in osteocytes-enriched bone fraction. It reduced 4-HNE staining area, stimulated Nrf2-positive staining, and promoted nuclear translocation of Nrf2 in osteocytes of mice as well as inhibited and promoted protein expression of 4-HNE and Nrf2, respectively, in osteocytes-enriched bone fraction. CONCLUSIONS: The present study revealed the ameliorative effects of eldecalcitol on senescence and the associated ferroptosis of osteocytes, contributing to its preservation against osteoporosis of D-gal-induced senescent ovariectomized mice.

A nanopore-based cucumber genome assembly reveals structural variations at two QTLs controlling hypocotyl elongation.

The Xishuangbanna (XIS) cucumber (Cucumis sativus var. xishuangbannanesis) is a semiwild variety that has many distinct agronomic traits. Here, long -reads generated by Nanopore sequencing technology helped assembling a high-quality genome (contig N50 = 8.7 Mb) of landrace XIS49. A total of 10,036 structural/sequence variations (SVs) were identified when comparing with Chinese Long (CL), and known SVs controlling spines, tubercles, and carpel number were confirmed in XIS49 genome. Two QTLs of hypocotyl elongation under low light, SH3.1 and SH6.1 were fine-mapped using introgression lines (donor parent, XIS49; recurrent parent, CL). SH3.1 encodes a red-light receptor Phytochrome B (PhyB, CsaV3_3G015190). An ∼4 kb large deletion (DEL) and highly divergent regions (HDRs) were identified in the promoter of the PhyB gene in XIS49. Loss of function of this PhyB caused a super-long hypocotyl phenotype. SH6.1 encodes a CCCH-type zinc finger protein FRIGIDA-ESSENTIAL LIKE (FEL, CsaV3_6G050300). FEL negatively regulated hypocotyl elongation but it was transcriptionally suppressed by a long terminal repeats (LTRs) retrotransposon insertion in CL cucumber. Mechanistically, FEL physically binds to the promoter of CONSTITUTIVE PHOTOMORPHOGENIC 1a (COP1a), regulating the expression of COP1a and the downstream hypocotyl elongation. These above results demonstrate the genetic mechanism of cucumber hypocotyl elongation under low light.

Biogenic volatile organic compounds dominated the near-surface ozone generation in Sichuan Basin, China, during fall and wintertime.

The complex air pollution driven by both Ozone (O3) and fine particulate matter (PM2.5) significantly influences the air quality in the Sichuan Basin (SCB). Understanding the O3 formation during autumn and winter is necessary to understand the atmospheric oxidative capacity. Therefore, continuous in-site field observations were carried out during the late summer, early autumn and winter of 2020 in a rural area of Chongqing. The total volatile organic compounds (VOCs) concentration reported by a Proton-Transfer-Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) were 13.66 ± 9.75 ppb, 5.50 ± 2.64 ppb, and 9.41 ± 5.11 ppb in late summer, early autumn and winter, respectively. The anthropogenic VOCs (AVOCs) and biogenic VOCs (BVOCs) were 8.48 ± 7.92 ppb and 5.18 ± 2.99 ppb in late summer, 3.31 ± 1.89 ppb and 2.19 ± 0.93 ppb in autumn, and 6.22 ± 3.99 ppb and 3.20 ± 1.27 ppb in winter. A zero-dimensional atmospheric box model was employed to investigate the sensitivity of O3-precursors by relative incremental reactivity (RIR). The RIR values of AVOCs, BVOCs, carbon monoxide (CO), and nitrogen oxides (NOx) were 0.31, 0.71, 0.09, and -0.36 for late summer, 0.24, 0.59, 0.22, and -0.38 for early autumn, and 0.30, 0.64, 0.33 and -0.70 for winter, and the results showed that the O3 formation of sampling area was in the VOC-limited region, and O3 was most sensitive to BVOCs (with highest RIR values, > 0.6). This study can be helpful in understanding O3 formation and interpreting the secondary formation of aerosols in the winter.

Coarse particles compensate for missing daytime sources of nitrous acid and enhance atmospheric oxidation capacity in a coastal atmosphere.

Large missing sources of daytime atmospheric nitrous acid (HONO), a vital source of hydroxyl radicals (OH) through its photolysis, frequently exist in global coastal regions. In this study, ambient HONO and relevant species were measured at a coastal site in the Pearl River Delta (PRD), China, during October 2019. Relatively high concentrations (0.32 ± 0.19 ppbv) and daytime peaks at approximately 13:00 of HONO were observed, and HONO photolysis was found to be the dominant (55.5 %) source of the primary OH production. A budget analysis of HONO based on traditional sources suggested large unknown sources during the daytime (66.4 %), which had a significant correlation with the mass of coarse particles (PM2.5-10) and photolysis frequency (J(NO2)). When incorporating photolysis of the abundant nitrate measured in coarse particles with a reasonable enhancement factor relative to fine particles due to favorable aerosol conditions, the missing daytime sources of HONO could be fully compensated by coarse particles serving as the largest source at this coastal site. Our study revealed great potential of coarse particles as a strong daytime HONO source, which has been ignored before but can efficiently promote NOx recycling and thus significantly enhance atmospheric oxidation capacity.

Retrievable Inferior Vena Cava Filter Trapped Embolus: A Risk Factor of Detachment of Thrombus Analysis Based on a Multicenter Prospective Observational Study.

PURPOSE: Up to now, the indications of inferior vena cava filter placement still remain controversial in the academic field. The aim of this study was to determine the risk factors of detachment of thrombus and to evaluate the necessity of inferior vena cava filter placement to prevent fatal pulmonary embolism. MATERIALS AND METHODS: A total of 2892 patients participated in the multicenter prospective observational study from January 1, 2018, to December 31, 2018, and underwent retrievable inferior vena cava filter (RIVCF) placement in 103 centers in China. The primary endpoint of the study was RIVCF trapped embolus detected by inferior vena cava venography/ultrasound/computed tomography scanning or visible macroscopic thrombus before or during RIVCF retrieval. The relative factors of RIVCF trapped embolus were analyzed accordingly. RESULTS: The average age of the patients was 61.0 (50.0-71.0) years. Retrievable inferior vena cava filter trapped embolus occurred in 308 patients (10.65%). The fracture location, surgery location, and endovascular intervention differed between RIVCF trapped embolus and non-RIVCF trapped embolus groups (p<0.001, respectively). By multivariate analysis, RIVCF trapped embolus were less common in older patients (odds ratio [OR]=0.998; p<0.001) and more common in patients with below-the-knee fracture (OR=1.093, p=0.038), thigh fracture (OR=1.118, p=0.007), and pelvis surgery (OR=1.067, p=0.016). In addition, compared with patients without endovascular intervention, patients with percutaneous mechanical thrombectomy (PMT) + catheter-directed thrombolysis (CDT) were more prone to develop RIVCF trapped embolus (OR=1.060, p=0.010). However, RIVCF trapped embolus was less common in patients with CDT (OR=0.961, p=0.004). CONCLUSIONS: Lower limb fracture, pelvis surgery, and PMT + CDT are prone to cause trapped embolus. As a trapped embolus often represents the possibility of severe pulmonary embolism, lower limb fracture, pelvis surgery, and PMT + CDT could be risk factors of fatal pulmonary embolism. Due to the low incidence of trapped embolus, it is not necessary to place filters in elderly patients and CDT-only patients. CLINICAL IMPACT: The purpose of this paper is to standardize the use of inferior vena cava filter and avoid unnecessary filter implantation through the summary and analysis of a large number of clinical data. At the same time, more attention should be paid to and active treatment should be given to high-risk groups of pulmonary embolism.

Impact of pre-ablation left appendage flow velocities on long term recurrence of catheter ablation for paroxysmal atrial fibrillation.

BACKGROUND: Despite undergoing a single ablation, many patients with paroxysmal atrial fibrillation (PAF) experience a gradually increasing recurrence rate. This study aims to examine the relationship between left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV) profiles and 3-year recurrence of AF after ablation. METHODS: We conducted a prospective study of 658 consecutive PAF patients who underwent their first ablation between January 2018 and December 2019. We collected the clinical and echocardiographic characteristics of the patients. LAAeV and LAAfV were obtained from a transesophageal echocardiogram (TEE) before catheter ablation. Patients were followed at regular intervals to monitor for the primary outcome of AF recurrence. RESULTS: After a median follow-up period of 35.3 months (range, 10.7-36.3), 288 patients (43.8%) experienced AF recurrence after catheter ablation. Patients who experienced AF recurrence had decreased LAAeV and LAAfV (LAAeV: 56.5 ± 21.2 vs. 59.6 ± 20.7 cm/s, p = .052; LAAfV: 47.5 ± 17.9 vs. 51.7 ± 18.2, p = .003). Kaplan-Meier analysis showed that patients in the low LAAeV (<55 cm/s) group had a poorer event-free survival rate than those in the high LAAeV (≥55 cm/s) group (log-rank p = .012). Patients with LAAfV <48 cm/s had a significantly higher risk of AF recurrence than those with LAAfV ≥48 cm/s (log-rank p = .003). In the multivariable model, low LAAfV pre-ablation in TEE-guided was significantly independently associated with 3-year recurrence after single radiofrequency ablation in patients with PAF, along with LA dimension and duration of AF. CONCLUSION: This study found an independent association between low LAAfV pre-ablation in TEE-guided and 3-year recurrence after single radiofrequency ablation in patients with PAF.

Microplastics in wastewater treatment plants and their contributions to surface water and farmland pollution in China.

Wastewater treatment plants (WWTPs) are usually considered gateways for microplastics (MPs) to enter the environment because large amounts of sewage are produced and MPs are incompletely removed during treatment processes. However, the contribution of effluent MPs to aquatic environmental pollution and that of sludge application to MPs in agricultural soil are still unknown. This study examines the presence of MPs in sewage and sludge in Shenzhen WWTPs and estimates the annual mass loading of MPs from WWTPs to surface water and farmland soil in China. According to our results, for Shenzhen, the annual contribution of MPs from WWTPs (which was obtained by multiplying the annual treated sewage volume by the estimated MP density in the treated sewage) to surface water could be 70.6-302 tons. With a normalized extrapolation model of population density, the contribution of national urban WWTPs to MPs in surface water was estimated to be 734 -3.10 × 103 tons/year, of which 220-950 tons/year entered the marine environment. Furthermore, the riverine flux of MPs from WWTPs to the ocean amounts to at least 7.0%-30% based on the maximum value of WWTP contribution to MPs in surface water. For sludge, the potential contribution of MPs to agricultural soil from Shenzhen WWTPs is (1.00-2.80) × 103 tons/year. With the above calculation procedure, it was estimated that the contribution of MPs to farmland from sludge application in China is (1.30-3.90) × 104 tons/year. The source appointment results for MPs in China's agricultural soil suggested that the contributions of the main four sources, namely, atmospheric deposition, agricultural mulch film, sludge application, and organic fertilizers, are 52%, 30%, 11%, and 7.0%, respectively.

[Research research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal hypoxic-ischemic encephalopathy]. / è¤ªé»‘ç´ è”åˆäºšä½Žæ¸©æ²»ç–—æ–°ç”Ÿå„¿ç¼ºæ°§ç¼ºè¡€æ€§è„‘ç— çš„ç ”ç©¶è¿›å±•.

Neonatal hypoxic-ischemic encephalopathy (HIE) remains one of the leading causes of death and long-term neurodevelopmental disorders in full-term neonates, and there is currently no curative treatment. Therapeutic hypothermia is now a standard therapy for HIE in the neonatal intensive care unit, but its safety and efficacy in remote areas remains unclear. Melatonin is an indole endocrine hormone mainly produced by the pineal gland and it has the ability to easily penetrate the blood-brain barrier. Through receptor and non-receptor mechanisms, melatonin exerts anti-oxidative and anti-inflammatory effects and participates in the regulation of organelle function and the inhibition of cell death. Melatonin is considered one of the most promising drugs for the treatment of HIE based on its reliable safety profile and clinical/preclinical results. This article reviews the recent research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal HIE.

Impact of age on characteristics, performance measures and outcomes of inpatients for heart failure in Beijing, China.

AIMS: This study aims to provide representative information on heart failure (HF) patients in China, especially older adults aged ≥75 years. We aim to clarify the age-related discrepancies in performance measures and the modifying effect of age on the impact of HF patients' characteristics on clinical outcomes. METHODS AND RESULTS: All HF patients admitted into five tertiary and four secondary hospitals of the Capital Medical University were divided into two groups according to age: 1419 (53.3%) were <75 years, and 1244 (46.7%) were ≥75 years. Older HF patients were more likely to be women, with higher left ventricular ejection fraction, with co-morbidities including chronic obstructive pulmonary disease/asthma, anaemia, chronic kidney disease, stroke/transient ischemic attack (TIA), atrial fibrillation/atrial flutter, hypertension, and coronary artery disease, while obesity, diabetes mellitus, hypercholesterolaemia and valvular heart disease were more prevalent among younger HF patients. Left ventricular ejection fraction assessment was performed in a similar proportion of patients in the younger and older groups (81.7% vs. 80.5%, P = 0.426), while B-type natriuretic peptide/N terminal pro brain natriuretic peptide was tested in a lower proportion in the younger group (84.8% vs. 89%, P = 0.001). At discharge, HF with reduced ejection fraction patients were less likely to receive beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, or combined beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers therapy in the older group (49.74% vs. 63.2%, P = 0.002; 52.9% vs. 64.7%, P = 0.006; and 28.57% vs. 45.5%, P < 0.001, respectively) but were equally likely to receive mineralocorticoid receptor antagonists in the two age groups (80.8% vs. 84.1%, P = 0.322). Older patients with HF had higher risk of in-hospital and 1 year mortality (2.7% vs. 1.3%, P = 0.011; 21.7% vs. 12.5%; P < 0.001, respectively). Higher body mass index was associated with better outcomes in both age groups. New York Heart Association functional class IV and estimated glomerular filtration rate < 60 mL/min/1.73 m2 were independent predictors of 1 year mortality. The associations between patients' characteristics and risk of mortality were not modified by age. CONCLUSIONS: HF patients aged ≥75 years had distinct clinical profiles, received worse in-hospital therapies and experienced higher in-hospital and 1 year mortality.

[Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study]. / æ¹–åŒ—æ©æ–½åœŸå®¶æ—è‹—æ—è‡ªæ²»å·žæ–°ç”Ÿå„¿çª’æ¯å±é™©å› ç´ åˆ†æžåŠåˆ—çº¿å›¾é¢„æµ‹æ¨¡åž‹çš„æž„å»ºï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS: The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

[Leukemia Genotype Analysis of Children with Acute Lymphoblastic Leukemia in Yunnan Area].

OBJECTIVE: To analyze 43 leukemia genes in children with acute lymphoblastic leukemia (ALL) in Yunnan province, and provide the basis for the diagnosis and treatment of children with ALL in this area. METHODS: The clinical data of 428 children with newly diagnosed ALL in Yunnan area from January 2015 to December 2020 were retrospectively analyzed. Multiple nested PCR technology was used to detect 43 common leukemia genes. RESULTS: Among the 428 children with ALL, 159 were positive for leukemia genes, with a positive rate of 37.15% (159/428), and a total of 15 leukemia genes were detected. Among the 159 leukemia gene-positive children, ETV6-RUNX1+ accounted for 25.79% (41/159), followed by E2A-PBX1+ and BCR-ABL+, accounting for 24.53% (39/159) and 23.27% (37/159) respectively. MLL+ accounted for 6.29% (10/159), WT1+ accounted for 4.40% (7/159), IKZF1 gene deletion and CRLF2+ accounted for 3.77% (6/159) respectively. The positive rate of MLL (46.15%) was the highest in ＜1-year old group, the positive rate of ETV6-RUNX1 (10.56%) was the highest in 1-10-year old group, and BCR-ABL+ rate (23.65%) was the highest in >10-year old group. The distribution of leukemia genes in different age groups was statistically significant (P <0.05). CONCLUSION: The most common fusion gene of children with ALL in Yunnan is ETV6-RUNX1, followed by E2A-PBX1 and BCR-ABL.

Seasonal variation characteristics of atmospheric peroxyacetyl nitrate (PAN) and its source apportionment in a megacity in southern China.

Owing to its biotoxicity and inductive effect on photochemical pollution, atmospheric peroxyacetyl nitrate (PAN), which is a typical product of atmospheric photochemical reactions, has attracted much research attention. However, to the best of our knowledge, few comprehensive studies have been conducted on the seasonal variation and key influencing factors of PAN concentrations in southern China. In this study, PAN, ozone (O3), precursor volatile organic compound (VOC), and other pollutant concentrations were measured online for 1 year (from October 2021 to September 2022) in Shenzhen, a megacity in the Greater Bay Area of China. The average concentrations of PAN and peroxypropionyl nitrate (PPN) were 0.54 and 0.08 parts per billion (ppb), and the maximum hourly concentrations reached 10.32 and 1.01 ppb, respectively. The results of the generalized additive model (GAM) showed that the atmospheric oxidation capacity and precursor concentration were the most important factors affecting the PAN concentration. According to the steady-state model, the average cumulative contribution to the peroxyacetyl (PA) radical formation rate by six major carbonyl compounds was calculated at 4.2 × 106 molecules cm-3 s-1, and acetaldehyde (63.0 %) and acetone (13.9 %) contributed the most. Furthermore, the photochemical-age-based parameterization method was used to analyze the source contributions of carbonyl compounds and PA radicals. The results showed that although the primary anthropogenic (40.2 %), biogenic (27.8 %), and secondary anthropogenic (16.4 %) sources were the most important contributors of PA radicals, the biogenic and secondary anthropogenic source contributions both increased considerably in summer, and the cumulative proportion of both sources reached ~70 % in July. In addition, a comparison of PAN pollution processes in different seasons revealed that in summer and winter, the PAN concentration was predominantly limited by precursors and meteorological parameters, such as light intensity, respectively.

Effect of birth asphyxia on neonatal blood glucose during the early postnatal life: A multi-center study in Hubei Province, China.

BACKGROUND: Birth asphyxia causes hypoxia or inadequate perfusion to the organs of newborns, leading to metabolism dysfunctions including blood glucose disorders. METHODS: Neonates with and without birth asphyxia were retrospectively recruited from 53 hospitals in Hubei Province from January 1 to December 31, 2018. In summary, 875, 1139, and 180 cases in the control group, the mild asphyxia group, and the severe asphyxia group were recruited, respectively. Neonatal blood glucose values at postnatal 1, 2, 6, and 12 h (time error within 0.5 h was allowed) were gathered from the medical records. RESULTS: The incidence rates of hyperglycemia in the control group, the mild asphyxia group and the severe asphyxia group were 2.97%, 7.90%, and 23.33%, respectively (p < 0.001). Additionally, the incidence rates of hypoglycemia in the three groups above were 3.66%, 4.13%, and 7.78%, respectively (p = 0.042). The blood glucose values of neonates with hypoglycemia in the asphyxia group were lower than in the control group (p = 0.003). Furthermore, the blood glucose values of neonates with hyperglycemia were highest in the severe asphyxia group (p < 0.001). There were 778 and 117 cases with blood glucose records at four predefined time points in the mild and severe asphyxia group, respectively. The incidence of blood glucose disorders in the mild asphyxia group significantly decreased from postnatal 6 h (p＜0.05). However, we found no obvious changes of the incidence of glucose disorders within postnatal 12 h in the severe asphyxia group (p = 0.589). CONCLUSION: Birth asphyxia is likely to cause neonatal blood glucose disorders, both hypoglycemia and hyperglycemia, during the early postnatal life. The neonates with severe asphyxia have higher incidence, worse severity and longer duration of blood glucose disorders than neonates with mild asphyxia.

Research progress on microbial control of sugarcane smut.

Sugarcane is the most important sugar crop. Sugarcane smut is one of the major diseases, which could reduce sugarcane yield and quality and seriously threaten the sustainable and healthy development of sugar industry. Microbial control of sugarcane smut is a rapidly emerging green biocontrol technology, with advantage to increase environmental compatibility and soil fertility. In this review, we briefly described the characteristics of Sporisorium scitamineum which causes sugarcane smut, synthesized the the mechanisms underlying the infection of sugarcane by S. scitamineum, and presented the research status of microbial controls of sugarcane smut via the application of bio-organic fertilizers and biopesticides. We then reviewed the mechanisms underlying the suppression of sugarcane smut by microorganisms through competition with pathogens for nutrients and ecological niches, secreting antagonistic substances, and improving plant resistance. It is notable that there are still some problems in the application of microbial control technologies, including poor colonization ability and unstable biocontrol efficiency. Finally, the major directions of future research on the biocontrol of sugarcane smut were proposed from the perspective of improving the biocontrol efficiency. This review would benefit the microbial control of sugarcane smut and the healthy development of sugar industry.

The effect of different frames filters on the prevention of pulmonary embolism in fracture patients subsequent with deep venous thrombosis on a multicenter prospective observational study.

BACKGROUND: A retrievable inferior vena cava filter (RIVCF) is used for the prevention of a pulmonary embolism, especially originated from deep venous thrombosis (DVT). However, which frame of RIVCF has an better effect on the specific thrombus has not been reported. METHODS: All patients enrolled underwent RIVCF placement in the study, and the placement and retrieval followed the respective instructions of different brands of RIVCFs. During the study period, the frame of the filter, the combined fracture site and operation, and the filter trapped embolus (TE) were collected. The primary observation indicators of this study were the occurrence of TE in two frames of filters and different fracture sites. Secondary observation indicators were the occurrence of TE with two different frames filters in different fracture site and surgical site subgroups. RESULTS: In all 2892 patients enrolled, RIVCF TE was detected in 308 cases (10.7%) according to our definition. Among them, there were 1968 cases of fusiform RIVCF and 924 cases of umbrella RIVCF. There were 663 patients combined with fractures before DVT. The incidence of TE was significantly higher in patients with fusiform RIVCF (230 [74.68%]) than in those with umbrella RIVCF (78 [25.32%]) (P < .05). In patients with below-the-knee fracture surgery, there was significant difference in the incidence of TE between the two frames of RIVCF (P < .05). CONCLUSIONS: This conclusion suggests that, in patients with DVT secondary to below-the-knee fracture, the detached thrombus may be more suitable for prophylaxis with fusiform frame RIVCF.

A novel machine learning method for evaluating the impact of emission sources on ozone formation.

Ambient ozone air pollution is one of the most important environmental challenges in China today, and it is particularly significant to identify pollution sources and formulate control strategies. In present study, we proposed a novel method of positive matrix factorization-SHapley Additive explanation (PMF-SHAP) for evaluating the impact of emission sources on ozone formation, which can quantify the main emission sources of ozone pollution. In this method, we first used the PMF model to identify the source of volatile organic compounds (VOCs), and then quantified various emission sources using a combination of machine learning (ML) models and the SHAP algorithm. The R2 of the optimal ML model in this method was as high as 0.96, indicating that the prediction performance was excellent. Furthermore, we explored the impact of different emission sources on ozone formation, and found that ozone formation in Shenzhen was more affected by VOCs, of which vehicle emission sources may have the greatest impact. Our results suggest that the appropriate combination of traditional models with ML models can well address environmental pollution problems. Moreover, the conclusions obtained based on the PMF-SHAP method were different from the traditional ozone formation potential (OFP) results, providing valuable clues for related mechanism studies.

Comparative Study of the Two High-Efficient Strategies for in vitro Generation of Human Umbilical Cord Blood-derived Natural Killer Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.