Effect of Miscellaneous Meals Replacing Soybean Meal in Feed on Growth Performance, Serum Biochemical Parameters, and Microbiota Composition of 25-50 kg Growing Pigs.

The present study aims to determine the effect of miscellaneous meals (rapeseed meal, cottonseed meal, and sunflower meal) replacing soybean meal in feed on growth performance, apparent digestibility of nutrients, serum biochemical parameters, serum free amino acid content, microbiota composition and SCFAs content in growing pigs (25-50 kg). A total of 72 (Duroc × Landrace × Yorkshire) growing pigs with initial weights of 25.79 ± 0.23 kg were randomly divided into three treatments. The pigs were fed corn-soybean meal (CON), corn-soybean-miscellaneous meals (CSM), and corn-miscellaneous meals (CMM). Each treatment included six replicates with four pigs per pen (n = 24, 12 barrows and 12 gilts). Soybean meal accounted for 22.10% of the basal diet in the CON group. In the CSM group, miscellaneous meals partially replaced soybean meal with a mixture of 4.50% rapeseed meal, 3.98% cottonseed meal, and 4.50% sunflower meal. In the CMM group, miscellaneous meals entirely replaced soybean meal with a mixture of 8.50% rapeseed meal, 8.62% cottonseed meal, and 8.5% sunflower. The results showed that compared with the CON, the CSM and CMM groups significantly improved the average daily gain (ADG) of growing pigs during the 25-50 kg stage (p < 0.05) but had no effects on average daily feed intake (ADFI) and average daily feed intake/average daily gain (F/G) (p > 0.05). Moreover, the CMM group significantly reduced nutrient apparent digestibility of gross energy compared with the CON group. The serum biochemical parameters results showed that the CSM group significantly improved the contents of total protein (TP) compared with the CON group (p < 0.05). The CMM group significantly improved the contents of total protein (TP), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) compared with the CON group in serum (p < 0.05). In comparison with the CON group, the CMM group also significantly improved lysine (Lys), threonine (Thr), valine (Val), isoleucine (Ile), leucine (Leu), phenylalanine (Phe), arginine (Arg), and citrulline (Cit) levels in serum (p < 0.05). However, the CMM group significantly decreased non-essential amino acid content glycine (Gly) in serum compared with CON (p < 0.05), while compared with the CON group, the CSM and CMM groups had no significant effects on the relative abundance, the alpha-diversity, or the beta-diversity of fecal microbiota. Moreover, compared with the CON group, the CSM group significantly increased butyric acid and valeric acid contents of short-chain fatty acids (SCFAs) in feces (p < 0.05). In contrast to the CON group, the CMM group significantly reduced the contents of SCFAs in feces, including acetic acid, propionic acid, and isobutyric acid (p < 0.05). Collectively, the results of the present study indicate that miscellaneous meals (rapeseed meal, cottonseed meal, and sunflower meal) can partially replace the soybean meal and significantly improve the growth performance of growing pigs during the 25-50 kg stage. Thus, miscellaneous meals are a suitable protein source as basal diets to replace soybean meals for 25-50 kg growing pigs. These results can be helpful to further develop miscellaneous meals as a functional alternative feed ingredient to soybean meal.

Effect of mixed meal replacement of soybean meal on growth performance, nutrient apparent digestibility, and gut microbiota of finishing pigs.

Introduction: This study was carried out to investigate the effects of mixed meal (rapeseed meal, cotton meal, and sunflower meal) replacement soybean meal on growth performance, nutrient apparent digestibility, serum inflammatory factors and immunoglobulins, serum biochemical parameters, intestinal permeability, short-chain fatty acid content, and gut microbiota of finishing pigs. Methods: A total of 54 pigs with an average initial weight of 97.60 ± 0.30 kg were selected and randomly divided into 3 groups according to their initial weight, with 6 replicates in each group and 3 pigs in each replicate. The trial period was 26 days. The groups were as follows: control group (CON), fed corn-soybean meal type basal diet; Corn-soybean-mixed meal group (CSM), fed corn-soybean meal-mixed meal diet with a ratio of rapeseed meal, cotton meal, and sunflower meal of 1:1:1 to replace 9.06% soybean meal in the basal diet; Corn-mixed meal group (CMM), fed a corn-mixed meal diet with a ratio of Rapeseed meal, Cotton meal and Sunflower meal of 1:1:1 to replace soybean meal in the basal diet completely. The crude protein level of the three diets was maintained at 12.5%. Results: Our findings revealed no significant impact of replacing soybean meal with the mixed meal (rapeseed meal, cotton meal, and sunflower meal) on the ADG (Average daily gain), ADFI (Average daily feed intake), and F/G (Feed gain ratio) (P > 0.05), or crude protein, crude fat, and gross energy (P > 0.05) in the diet of finishing pigs. Compared with the CON group, the serum interleukin 6 (IL-6) and interleukin 10 (IL-10) concentrations were significantly decreased in the CMM group (P < 0.05). However, there is no significant effect of the mixed meal (rapeseed meal, cotton meal, and sunflower meal) replacing soybean meal in the diet on the serum interleukin 1ß (IL-1ß), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF-α), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations (P > 0.05). Concordantly, there is no significant effect of mixed meal (rapeseed meal, cotton meal, and sunflower meal) replacing soybean meal in the diet on the serum antioxidant capacity, such as total antioxidant capacity (T-AOC), catalase (CAT), and malondialdehyde (MDA) levels of finishing pigs. Moreover, compared with the CON group, serum low-density lipoprotein (LDL-C) levels were significantly lower in the CSM group (P < 0.05) and their total bilirubin (TBIL) levels were significantly lower in the CMM group (P < 0.05). There is not a significant effect on serum D-lactate and diamine oxidase (DAO) concentrations (P > 0.05). The next section of the survey showed that the replacement of soybean meal with a mixed meal (rapeseed meal, cotton meal, and sunflower meal) in the diet did not significantly influence the acetic acid, propionic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid in the colon contents (P > 0.05). Furthermore, compared with the CON group, the CMM group diet significantly increased the abundance of Actinobacteria at the phylum level (P < 0.05), U_Actinobacteria at the class level (P < 0.05), and U_Bacteria at the class level (P < 0.05). The result also showed that the CMM group significantly reduced the abundance of Oscillospirales at the order level (P < 0.05) and Streptococcaceae at the family level (P < 0.05) compared with the CON group. The Spearman correlation analysis depicted a statistically significant positive correlation identified at the class level between the relative abundance of U_Bacteria and the serum T. BILI concentrations (P < 0.05). Moreover, a significant negative correlation was detected at the order level between the relative abundance of Oscillospirales and the levels of acetic and propionic acids in the colonic contents (P < 0.05). Additionally, there was a significant positive correlation between the serum concentrations of IL-6 and IL-10 and the relative abundance of the family Streptococcaceae (P < 0.05). Discussion: This study demonstrated that the mixed meal (rapeseed meal, cotton meal, and sunflower meal) as a substitute for soybean meal in the diet had no significant negative effects on the growth performance, nutrient apparent digestibility, serum immunoglobulins, serum antioxidant capacity, intestinal permeability, short-chain fatty acid content, and diversity of gut microbiota of finishing pigs. These results can help develop further mixed meals (rapeseed meal, cotton meal, and sunflower meal) as a functional alternative feed ingredient for soybean meals in pig diets.

Modified Chinese disabilities of arm, shoulder and hand tool: Validity and reliability for upper extremity injuries.

DESIGN: Clinimetric evaluation study. INTRODUCTION: The Chinese Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire has necessitated the development of a revised version to the specific needs of individuals with upper extremity injuries with the progress of times and lifestyle changes. PURPOSE OF THE STUDY: This research aimed to evaluate the reliability and validity of Modified Chinese Disability of Arm, Shoulder and Hand (MC-DASH) questionnaire in individuals with upper extremity injuries. METHODS: One hundred and one individuals with upper extremity injuries (UEI) were recruited. The function of upper extremity was measured using the electronic version of MC-DASH, and compared against the Chinese Disability of Arm, Shoulder and Hand. The MC-DASH was reassessed within three days in all individuals. We investigated the internal consistency, test-retest reliability, content validity, criterion validity, and construct validity of MC-DASH. RESULTS: The internal consistency was deemed sufficient, as indicated by a Cronbach's alpha of 0.986 and an intraclass correlation coefficient of 0.957. Moreover, the mean total scores of MC-DASH on the first-test and retest were 37.86 and 38.19, respectively (ICC: 0.957, 95 %CI: 0.937-0.971, p < 0.001). Furthermore, the MC-DASH version exhibited satisfactory content validity evidenced by its strong correlation (R= 0.903, p < 0.001) with the Chinese DASH. Three major influencing factors were identified from 37 items. The cumulative variance contribution rate of the MC-DASH questionnaire was 75.76 %, confirming its construct validity. CONCLUSION: The Modified Chinese Disability of Arm, Shoulder and Hand questionnaire has been shown to be a valid, reliable, and practical tool for use in patients with upper extremity injuries.

Effect of traumatic upper-limb injury on cognitive functions: A cross-sectional observational study.

OBJECTIVES: There is growing evidence of cognitive impairment after traumatic peripheral lesions. The purpose of this study was to explore the association between cognitive function and traumatic upper-limb injury. We assessed difference in cognitive function between participants with and without upper-limb injury, and explored the association between cognitive function and certain variables in injured individuals: gender, age, body mass index (BMI), educational level, and occupation. We sought to identify the factors associated with cognitive function in injured subjects: time since injury, injury side, nerve injury, hand function, pain, and finger sensation. MATERIAL AND METHODS: A cross-sectional observational study was conducted, with 2 groups: observational group (with traumatic upper-limb injury) and control group (uninjured). The 2 groups were matched for age, gender, BMI, educational level and occupation. Short-term memory and executive functions were assessed using the Rey Auditory and Verbal Learning Test (RAVLT) and Stroop Color and Word Test (SCWT), respectively. RESULTS: 104 participants with traumatic upper-limb injury and 104 uninjured control subjects were included. There was a significant inter-group difference only in RAVLT (p < 0.01; Cohen d, of 0.38). Regression analysis demonstrated an association of pain on VAS (beta = -0.16, p < 0.01) and touch-test (beta = 1.09, p < 0.05) with total RAVLT score (short-term memory) in injured subjects (R2 = 0.19, F (2, 82) = 9.54, p < 0.001). CONCLUSION: Traumatic upper-limb injury can impact short-term memory, which should be kept in mind during rehabilitation.

The delayed clearance of Talaromyces marneffei in blood culture may be associated with higher MIC of voriconazole after antifungal therapy among AIDS patients with talaromycosis.

OBJECTIVES: This study aimed to investigate the influencing factors of delayed clearance of Talaromyces marneffei (T. marneffei) in blood culture of patients with acquired immune deficiency syndrome (AIDS) complicated with talaromycosis after antifungal therapy. METHODS: The patients with AIDS complicated with talaromycosis were retrospectively enrolled, and divided into two groups according to the blood T. marneffei culture results in two weeks after antifungal therapy. The baseline clinical data were collected and the antifungal susceptibility of T. marneffei was tested. RESULTS: A total of 190 patients with AIDS and talaromycosis were enrolled, of whom 101 cases remained positive for T. marneffei (Pos-group) while the other 89 cases were negative in blood culture (Neg-group) after two weeks' antifungal treatment. The Pos-group had a higher baseline Aspartate aminotransferase (AST, 78.5 vs. 105 U/L; P = 0.073) and lower CD4+ T cells level (11 vs. 7 cells/µl; P = 0.061). The percentage of isolates with higher MICs of voriconazole (VOR) and fluconazole (FLU) in the Pos-group were significantly higher than those in the Neg-group (χ2 = 12.623, P < 0.001 and χ2 = 9.356, P = 0.002, respectively). By multivariate logistic regression, the MIC value for VOR was identified as the prognostic variable that may influence the clearance of T. marneffei in blood culture after antifungal therapy among AIDS patients with talaromycosis. CONCLUSIONS: The delayed negative conversion of blood T. marneffei-culture may be associated with some factors especially higher MIC of VOR, indicating the possibility of drug resistance of T. marneffei.

Transcriptome analysis of CD4+ T cells from HIV-infected individuals receiving ART with LLV revealed novel transcription factors regulating HIV-1 promoter activity.

Some HIV-infected individuals receiving ART develop low-level viremia (LLV), with a plasma viral load of 50-1000 copies/mL. Persistent low-level viremia is associated with subsequent virologic failure. The peripheral blood CD4+ T cell pool is a source of LLV. However, the intrinsic characteristics of CD4+ T cells in LLV which may contribute to low-level viremia are largely unknown. We analyzed the transcriptome profiling of peripheral blood CD4+ T cells from healthy controls (HC) and HIV-infected patients receiving ART with either virologic suppression (VS) or LLV. To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV, KEGG pathways of differentially expressed genes (DEGs) were acquired by comparing VS with HC (VS-HC group) and LLV with VS (LLV-VS group), and overlapped pathways were analyzed. Characterization of DEGs in key overlapping pathways showed that CD4+ T cells in LLV expressed higher levels of Th1 signature transcription factors (TBX21), toll-like receptors (TLR-4, -6, -7 and -8), anti-HIV entry chemokines (CCL3 and CCL4), and anti-IL-1ß factors (ILRN and IL1R2) compared to VS. Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription. Finally, we evaluated the effects of 4 and 17 transcription factors that were upregulated in the VS-HC and LLV-VS groups, respectively, on HIV-1 promoter activity. Functional studies revealed that CXXC5 significantly increased, while SOX5 markedly suppressed HIV-1 transcription. In summary, we found that CD4+ T cells in LLV displayed a distinct mRNA profiling compared to that in VS, which promoted HIV-1 replication and reactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV. CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.

Adoptive immune transfer from donors offers Anti-HBV protection to HBsAb-negative patients after Allo-HSCT.

Adoptive transfer of hepatitis B virus (HBV) immunity may occur following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we investigated the adoptive transfer of HBV immunity in 112 patients without HBV surface antibody (HBsAb) (HBsAb-) at the time of their first allo-HSCT. After allo-HSCT, HBV-DNA（87.5%） and HBsAg（11.1%%）cleared in HBsAg+ patients. All HBsAg- patients acquired HBsAb immediately. Nevertheless, HBsAb titers subsequently declined, and 39/67 (58.2%) patients lost HBsAb during follow-up. The 5-year overall survival (OS) was better in patients who lost HBsAb. Multivariate analysis showed that the independent risk factors for OS were lack of cytomegalovirus (CMV) clearance, acute graft-versus-host disease (aGVHD), and no HBsAb loss. Overall, adoptive immune transfer offers anti-HBV protection to patients without HBsAb, as they acquire HBsAb and clear HBV-DNA and HBsAg, while HBsAb loss after allo-HSCT predicts better survival.

Professional Identity among New Rehabilitation Graduates in China: A Cross-Sectional Questionnaire-Based Survey.

Background: The rehabilitation industry suffered in a terrible economic climate caused by the coronavirus disease 2019 (COVID-19). Healthcare resources and the labor force were directed towards epidemic prevention of post-pandemic, which exacerbated the issue. This study evaluated the professional identity (PI) of new graduates majoring in rehabilitation therapy during the final harsh phase of COVID-19 and explored the factors influencing PI. Methods: A cross-sectional investigation with a questionnaire was used in this study. A convenience sample of new graduates who majored in rehabilitation were recruited from hospitals and universities nationwide. The data collected demographic information and scores of professional identities for students in the final phase of the strict COVID-19 control policy in 2022. Results: This study indicated that the average PI was quite a distance from the degree of 'agree' (3.84 on average), particularly for the fitness dimension (3.64 on average). The results identified two influencing variables: employment (Beta= -0.09, P< 0.05) and educational patterns (Beta= 0.12, P< 0.01). Conclusions: Higher education in rehabilitation should respond to the present shift in the structure of the rehabilitation industry post-COVID-19. Meanwhile, the occupational environment of rehabilitation therapists and the medical value of rehabilitation therapy deserves more attention. This study provides evidence for managers to improve organizational justice and adjust policies on the distribution of medical resources.

DITES: A Lightweight and Flexible Dual-Core Isolated Trusted Execution SoC Based on RISC-V.

A Trusted Execution Environment (TEE) is an efficient way to secure information. To obtain higher efficiency, the building of a dual-core system-on-chip (SoC) with TEE security capabilities is the hottest topic. However, TEE SoCs currently commonly use complex processor cores such as Rocket, resulting in high resource usage. More importantly, the cryptographic unit lacks flexibility and ignores secure communication in dual cores. To address the above problems, we propose DITES, a dual-core TEE SoC based on a Reduced Instruction Set Computer-V (RISC-V). At first, we designed a fully isolated multi-level bus architecture based on a lightweight RISC-V processor with an integrated crypto core supporting Secure Hashing Algorithm-1 (SHA1), Advanced Encryption Standard (AES), and Rivest-Shamir-Adleman (RSA), among which RSA can be configured to five key lengths. Then, we designed a secure boot based on Chain-of-Trust (CoT). Furthermore, we propose a hierarchical access policy to improve the security of inter-core communication. Finally, DITES is deployed on a Kintex 7 Field-Programmable-Gate-Array (FPGA) with a power consumption of 0.297 W, synthesized using TSMC 90 nm. From the results, the acceleration ratios of SHA1 and RSA1024 decryption/encryption can reach 75 and 1331/1493, respectively. Compared to exiting TEE SoCs, DITES has lower resource consumption, higher flexibility, and better security.

Can Published Population Pharmacokinetic Models of Busulfan Be Used for Individualized Dosing in Chinese Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation? An External Evaluation.

Busulfan is a bifunctional alkylating agent that is widely used before hematopoietic stem cell transplantation (HSCT), in combination with other chemotherapeutic drugs. As of 2020, there is no population pharmacokinetic (popPK) model for busulfan in Chinese pediatric patients. A systemic external evaluation of 11 published popPK models was conducted in Chinese pediatric patients undergoing HSCT. Forty pediatric patients were enrolled in this study, with a total of 183 blood concentrations. The relative prediction error (PE%), median PE%, median absolute PE%, and percentage of PE% within ±20% and ±30% were calculated in prediction-based diagnostics. Simulation-based diagnostics were conducted through a prediction- and variability-corrected visual predictive check and the normalized prediction distribution error. The relative individual prediction error was calculated using Bayesian forecasting with 1 to 3 concentration points. The 1-compartment open linear popPK model, which was built by Su-jin Rhee et al (model H), incorporating the patient's body surface area, age, dosing day, and aspartate aminotransferase as significant covariates had preferable predictability than other popPK models. In prediction-based diagnostics, the median PE%, percentage of PE% within ±20%, and percentage of PE% within ±30% of model H were 8.48%, 45.35%, and 59.56%, respectively. The normalized prediction distribution error of model H showed that it followed the normal distribution. Based on Bayesian forecasting, model H showed good predictive performance. Thus, model H was the most appropriate model that can be used clinically for individualized dosage adjustments in Chinese pediatric HSCT patients.

Association of iKIR-mismatch model and donor aKIRs with better outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia.

Objectives: Killer cell immunoglobulin like receptor (KIR) can trigger the alloreactivity of NK cells. However, there is no clear consensus as to their function. Here, we investigated the potential influence of KIR mismatch and KIR alleles on the outcome of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in acute myeloid leukemia (AML) patients. Method: Data from 79 AML patients treated with haplo-HSCT were retrospectively analyzed. HLA-C genotyping was determined by the PCR-rSSO method. KIR, HLA-A and HLA-B genotyping was performed by the PCR-SSP method. Cox proportional hazards model and Kaplan-Meier survival curves were used for analysis. Results: Both KIR ligand mismatch (KLM) group and KIR receptor-ligand mismatch (RLM) group were associated with a decreased risk in aGVHD and relapse rate (RR), and better overall survival (OS) compared to the KIR ligand matching and receptor-ligand matching groups, respectively (aGVHD: KLM: p=0.047, HR:0.235; RLM: p<0.001, HR:0.129; RR: KLM: p=0.049, HR:0.686, RLM: p=0.017, HR:0.200;OS:KLM: p=0.012, HR: 0.298, RLM: p=0.021, HR:0.301). RLM was more accurate at predicting relapse and aGVHD compared with KLM (aGVHD: p=0.009; RR: p=0.039). Patients with greater number of donor activating KIRs (aKIR) had a lower incidence of aGVHD and relapse, and the benefits correlated with the increase in the number of donor aKIRs (aGVHD: p=0.019, HR:0.156; RR: p=0.037, HR:0.211). Patients with RLM and the highest number of donor aKIRs had the lowest RR, lowest incidence of aGVHD and best OS. Conclusions: Both KLM and RLM reduced the risk of aGVHD and relapse after haplo-HSCT in AML patients, and RLM showed superiority in predicting HSCT outcome. The synergistic effects of RLM and donor aKIRs can provide a better donor selection strategy to improve haplo-HSCT outcome in AML patients.

Predicting mortality from intracranial hemorrhage in patients who undergo allogeneic hematopoietic stem cell transplantation.

Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, a total of 70 allo-HSCT patients with an ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with an ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. These 2 cohorts were used to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors (lactate dehydrogenase level, albumin level, white blood cell count, and disease status) were retained in the multivariable logistic regression model, and a simplified grading scale (termed the LAWS score) was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, P > .05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic, 0.859; 95% confidence interval, 0.776-0.945) and the external validation cohort (C-statistic, 0.795; 95% confidence interval, 0.645-0.945). The LAWS score is the first scoring system capable of predicting 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups.

A practical update on the epidemiology and risk factors for the emergence and mortality of bloodstream infections from real-world data of 3014 hematological malignancy patients receiving chemotherapy.

Background: Bloodstream infection (BSI) is a common and serious complication after patients with hematologic malignancies (HM) receiving chemotherapy. This study examined real-world data seeking to characterize HM BSI and identify risk factors for BSI emergence and mortality. Methods: We retrospectively analyzed the pathogenic epidemiology, antibiotic resistance, and BSI risk factors in a single-center cohort including 3014 consecutive patients with HM receiving chemotherapy between 2013 and 2016. Results of the pathogenic epidemiology were validated via comparison to available reported data. Results: We found that 725 patients (24.1%) had BSIs. Gram-negative (G-) bacteria represented 64.7% of the 744 isolated pathogenic strains, while Gram-positive (G+) bacteria and fungi accounted for 27.7% and 7.7% of the BSIs, respectively. The most common isolates were Klebsiella pneumoniae (19.2%), and 95.1% of the multidrug-resistant strains (MDR) were extended-spectrum beta-lactamase producing strains. G- bacteria were the main microflora responsible for BSI in our cohort of Chinese HM patients compared to studies in developed countries or in neutropenic children with HM or solid tumors. Multivariate analysis revealed that male sex, age ≥ 45 and < 65 yr, hospital length of stay ≥ 9d, neutropenia ≥ 7d before cultures, ≥ 2 antibiotics, and infections (gastrointestinal, perirectal, or urinary tract) independently predicted BSI emergence. Furthermore, age ≥ 65 yr, neutropenia ≥ 7d before blood cultures, no HM remission, lower white blood cell count, ≥ 3 antibiotics, respiratory infections, and Acinetobacter baumannii and Stenotrophomonas maltophilia BSI were independent predictors of 30-day mortality. Conclusions: G- bacteria were the predominant microflora during the study period and antibiotic resistance levels of the pathogens detected were high, especially for MDR strains. The mortality of BSI patients was high in this large cohort. Close attention should be paid to the risk factors identified here to facilitate timely and effective clinical management of such patients.

Broadly neutralizing antibody-derived CAR T cells reduce viral reservoir in individuals infected with HIV-1.

BACKGROUNDChimeric antigen receptor (CAR) T cells have emerged as an approach to treat malignant tumors. This strategy has also been proposed for the treatment of HIV-1 infection. We have developed a broadly neutralizing antibody-derived (bNAb-derived) CAR T cell therapy that can exert specific cytotoxic activity against HIV-1-infected cells.METHODSWe conducted an open-label trial of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of bNAb-derived CAR T cell therapy in individuals infected with HIV-1 who were undergoing analytical interruption of antiretroviral therapy (ART).RESULTSA total of 14 participants completed only a single administration of bNAb-derived CAR T cells. CAR T cell therapy administration was safe and well tolerated. Six participants discontinued ART, and viremia rebound occurred in all of them, with a 5.3-week median time. Notably, the cell-associated viral RNA and intact proviruses decreased significantly after CAR T cell treatment. Analyses of HIV-1 variants before or after CAR T cell administration suggested that CAR T cells exerted pressure on rebound viruses, resulting in a selection of viruses with less diversity and mutations against CAR T cell-mediated cytotoxicity.CONCLUSIONNo safety concerns were identified with adoptive transfer of bNAb-derived CAR T cells. They reduced viral reservoir. All the rebounds were due to preexisting or emergence of viral escape mutations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03240328).FUNDINGMinistry of Science and Technology of China, National Natural Science Foundation of China, and Department of Science and Technology of Guangdong Province.

Iron overload as a risk factor for poor graft function following allogeneic hematopoietic stem cell transplantation.

Hematological malignancies are increasingly treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, iron overload is a frequent adverse effect of allo-HSCT and is associated with poor prognosis. In the present study, we investigated hematopoiesis in iron-overloaded mice and elucidated the effects of iron overload on the bone marrow (BM) microenvironment. Iron-overloaded BALB/C mice were generated by injecting 20 mg/mL saccharated iron oxide intraperitoneally. Hematoxylin-eosin staining was performed to evaluate the effects of an iron overload in mice. BM cells obtained from C57BL/6 mice were transplanted into irradiated BALB/C mice (whole-body irradiation of 4 Gy, twice with a 4-hours interval) by tail vein injection. Two weeks after allo-HSCT, the hematopoietic reconstitution capacity was evaluated in recipients by colony-forming assays. Histopathological examinations showed brown-stained granular deposits, irregularly arranged lymphocytes in the liver tissues, and blue-stained blocks in the BM collected from mice received injections of high-dose saccharated iron oxide (20 mg/mL). Iron-overloaded mice showed more platelets, higher-hemoglobin (HGB) concentration, fewer granulocyte-macrophage colony-forming units (CFU-GM), erythrocyte colony-forming units (CFU-E), and mixed granulocyte/erythrocyte/monocyte/megakaryocyte colony-forming units (CFU-mix) than healthy mice. Iron-overloaded recipients presented with reduced erythrocytes and HGB concentration in peripheral blood, along with decreased marrow stroma cells, CFU-GM, CFU-E, and CFU-mix relative to healthy recipients. Taken together, our findings demonstrate that iron overload might alter the number of red blood cells after transplantation in mice by destroying the BM microenvironment, thereby affecting the recovery of BM hematopoietic function.

Epidermal growth factor stimulates exosomal microRNA-21 derived from mesenchymal stem cells to ameliorate aGVHD by modulating regulatory T cells.

Regulatory T cells (Tregs), a subset of CD4+ T cells, may exert inhibitory effects on alloimmune responses including acute graft-versus-host disease (aGVHD), and several microRNAs are implicated in the pathophysiological process of GVHD. Therefore, we aimed in the present study to characterize the functional relevance of epidermal growth factor (EGF)-stimulated microRNA-21 (miR-21) in regulating bone marrow-derived mesenchymal stem cells (BMSCs) in a mouse model of aGVHD. We first isolated and cultured BMSCs and Tregs. Then, we examined effects of miR-21 knockdown or overexpression and EGF on cell activities of BMSCs and the expression of PTEN, Foxp3, AKT phosphorylation, and extent of c-jun phosphorylation by gain- and loss-of-function approaches. The results showed that miR-21 promoted the proliferation, invasion, and migration of BMSCs. Furthermore, miR-21 in BMSCs-derived exosomes inhibited PTEN, but enhanced AKT phosphorylation and Foxp3 expression in Tregs. In addition, EGF enhanced c-jun phosphorylation to elevate the miR-21 expression. Furthermore, EGF significantly increased the efficacy of BMSCs in a mouse model of aGVHD, manifesting in reduced IFN-γ expression and lesser organ damage. Moreover, EGF treatment promoted the Foxp3 expression of Tregs in BMSCs-treated aGVHD mice. Taken together, EGF induced the BMSCs-derived exosomal miR-21 expression, which enhanced Foxp3 expression in Tregs, thereby improving the therapeutic effect of BMSCs on aGVHD.

Bone marrow mesenchymal stem cells alleviate the daunorubicin-induced subacute myocardial injury in rats through inhibiting infiltration of T lymphocytes and antigen-presenting cells.

INTRODUCTION: Bone marrow mesenchymal stem cells (BMSCs) have been extensively investigated from a perspective on cardiac regeneration therapy. The current study aimed to investigate the protective effect conferred by BMSCs in subacute myocardial injury, and to identify an appropriate BMSC reinfusion time. METHODS: BMSCs were isolated from human bone marrow blood. Daunorubicin (DNR)-induced subacute myocardial models were subsequently established. The rats with DNR-induced subacute myocardial injury were injected with dexrazoxane (DZR) and/or BMSCs at varying time points, after which cardiac function was evaluated by assessing left ventricular ejection fraction (LVEF) and fraction shortening (FS). The myocardial structural changes were analyzed, after which the levels of CD3 and human leukocyte antigen DR (HLA-DR) were examined to further validate the mechanism by which BMSCs could influence subacute myocardial injury. RESULTS: BMSCs combined with DZR treatment enhanced the cardiac function of rats with DNR-induced myocardial injury, as reflected by increased LVEF and FS. DNR-induced myocardial injuries were mitigated via the application of BMSCs combined with treatment of DZR, accompanied by diminished infiltration or vacuolization. Moreover, BMSCs were observed to alleviate infiltration of T lymphocyte and antigen-presenting cells, as evidenced by reduced expression of CD3 and HLA-DR. CONCLUSION: Taken together, this study demonstrates that BMSCs could protect against DNR-induced myocardial injury, especially in the first three days of DNR administration. BMSCs combined with DZR exert a better therapeutic effect, but there are individual differences.

The Effect of Judo Training on Set-Shifting in School Children.

Improving executive functions (EFs) is desirable as they are considered to be critical for academic attainment and mental wellness in children. The aim of this study was to explore the effect of Judo training on the set-shifting function using a spatial task-switching paradigm. Protocol 1 compared the set-shifting ability of Judo players with age-matched healthy individuals. Protocol 2 compared the difference in EFs between children who underwent Judo training (intervention) and age-matched controls. EFs were assessed by a spatial task-switching test. Error rates and response times were analysed using two-way repeated-measures ANOVA. Protocol 1. The group effect on error rates was significant. The trial type × group effect was significant in the Judo group. Error rates in the Judo group were lower in the switch trials than the control group (p = 0.001). No significant group difference was seen in the repeat trials (p = 0.764). Protocol 2. The time × trial type × group effect was significant. Post hoc analysis showed significantly lower error rates by the intervention group on switch trials compared to the control group (p = 0.006). Regular Judo training may potentially be an option for improving EFs in schoolchildren or in populations with executive dysfunction.