Intensive chemotherapy with dual induction and ALL-like consolidation for childhood acute myeloid leukemia: a respective report from multiple centers in China.

Background: Pediatric acute myeloid leukemia (AML) has poor prognosis and high rate of relapse and mortality, and exploration of new treatment options is still critically needed. Objectives: To summarize the outcome of our new treatment strategies for pediatric AML, which is characterized by dual induction and acute lymphoblastic leukemia (ALL) elements consolidation. Design: Retrospective, single-arm study. Methods: From July 2012 to December 2019, an intensive chemotherapy protocol was used for newly diagnosed children with AML, which contains dual induction, three courses of consolidations based on high-dose cytarabine, and two courses of consolidations composed of high-dose methotrexate, vincristine, asparaginase, and mercaptopurine (ALL-like elements). Blasts were monitored by bone marrow smears at intervals, and two lumbar punctures were performed during chemotherapy. We retrospectively analyzed the efficacy and safety of this study. The last follow-up was on 26 May 2023. Results: A total of 70 pediatric AMLs were included. The median age at diagnosis was 6.7 (0.5-16.0) years. The median initial WBC count was 23.74 × 109/L, 11 of whom ⩾100 × 109/L. After dual induction, there were 62 cases of complete remission (CR), 5 cases of partial remission, and 3 cases of nonremission. The CR rate was 88.57%. The median follow-up time was 5.8 (0.2-9.4) years, the 5-year overall survival was 78.2% ± 5%, the event-free survival (EFS) was 71.2% ± 5.6%, and the cumulative recurrence rate was 27.75%. The 5-year EFS of patients with initial WBC < 100 × 109/L (n = 59) and ⩾100 × 109/L (n = 11) were 76.4% ± 5.7% and 45.5% ± 15% (p = 0.013), respectively. A total of 650 hospital infections occurred. The main causes of infection were respiratory tract infection (26.92%), septicemia (18.46%), stomatitis (11.85%), and skin and soft-tissue infection (10.46%). Conclusion: This intensive treatment protocol with dual induction and ALL-like elements is effective and safe for childhood AML. Initial WBC ⩾ 100 × 109/L was the only independent risk factor in this cohort. Trial registration: It is a retrospective study, and no registration on ClinicalTrials.gov.

Characteristics of phosgene aspiration lung injury analyzed based on transcriptomics and proteomics.

Background: Phosgene is a chemical material widely used worldwide. No effective method has been developed to reverse its pathological injuries. Some studies have shown that neuronal inflammation in lung tissue is involved, but the specific mechanism has not been reported. Objective: To analyze the expression alterations of whole transcriptome gene sequencing bioinformatics and protein expression profile in lung tissue after phosgene aspiration lung injury (P-ALI) and find the main factors and pathways affecting the prognosis of P-ALI. Methods: Rat models of P-ALI were made by phosgene. Rats were divided into a P-ALI group and a blank group. Hematoxylin-eosin (HE) staining and lung wet/dry ratio measurement were used to evaluate the lung injury. The levels of inflammatory factors were measured by ELISA. High-throughput sequencing was used to measure the expression profile of each gene. Protein expression profiles were determined by label-free relative quantification of the differential proteome. Results: Lung injury such as the disordered structure of alveolar wall and inflammatory factors (IL-1ß, IL-18, and IL-33) were significantly increased in the P-ALI group (p < 0.05). There were 225 differentially expressed lncRNAs, including 85 upregulated and 140 downregulated genes. They were also the genomes with the most significant changes in transcriptome gene expression, mainly constituting cytoplasmic, synaptic structures and transporters, and involved in amino acid and carbon metabolism. There were 42 differentially expressed circRNAs, including 25 upregulated genes and 17 downregulated genes, mainly involved in cell composition, growth, differentiation, and division. There were only 10 differentially expressed miRNAs genes, all upregulated and mainly involved in the inflammatory response pathway. Proteome identification showed 79 differentially expressed proteins. KEGG enrichment analysis showed that it was mainly involved in the N-glycan biosynthesis pathway. Conclusion: We discovered that differentially regulated genes (lncRNAs, circRNAs, and miRNAs) were primarily associated with neuronal reflexes and synaptic signaling, including neurotransmitter transmission, ion signaling pathway conduction, neuronal projection, and synaptic vesicle circulation. They affected inflammatory factors and other metabolic pathways. This finding could be explored in future studies.

In vitro generation of genetic diversity for directed evolution by error-prone artificial DNA synthesis.

Generating genetic diversity lies at the heart of directed evolution which has been widely used to engineer genetic parts and gene circuits in synthetic biology. With the ever-expanding application of directed evolution, different approaches of generating genetic diversity are required to enrich the traditional toolbox. Here we show in vitro generation of genetic diversity for directed evolution by error-prone artificial DNA synthesis (epADS). This approach comprises a three-step process which incorporates base errors randomly generated during chemical synthesis of oligonucleotides under specific conditions into the target DNA. Through this method, 200 ~ 4000 folds of diversification in fluorescent strength have been achieved in genes encoding fluorescent proteins. EpADS has also been successfully used to diversify regulatory genetic parts, synthetic gene circuits and even increase microbial tolerance to carbenicillin in a short time period. EpADS would be an alternative tool for directed evolution which may have useful applications in synthetic biology.

Prognostic value and immunological function of cuproptosis-related genes in lung adenocarcinoma.

Background: Lung cancer is one of the malignant tumors with the highest morbidity and fatality rates worldwide. The overall survival (OS) of lung adenocarcinoma (LUAD) is poor. Cuproptosis is a copper-triggered modality of mitochondrial cell death, however, its contribution to the emergence of lung cancer is unknown. The clinical implication and immunological function of cuproptosis-related genes (CRGs) in LUAD has yet to be established. Methods: TCGA, HPA, GEPIA, Kaplan-Meier, TIMER and CancerSEA database were used to explore the prognostic value and biological function of CRGs in LUAD. Results: CRGs are primarily involved in copper ion transport, the citrate cycle (TCA cycle) and central carbon metabolism in LUAD. The mRNA expression of COA6, UBE2D1, DLAT, SLC25A3, and DBH was significantly increased. The expression of COA6, DLAT, SLC25A3, DBH, and LOXL2 were all strongly associated with the clinicopathological stages in LUAD. Moreover, high expression of COA6, UBE2D1, DLAT, SLC25A3 and LOXL2 was related to poor OS. The expression of SLC25A3 and LOXL2 showed different association with immune cell infiltration. The single cell sequencing demonstrated that CRGs play important roles in the regulation of DNA damage response, inflammation and metastasis in LUAD. Conclusions: In summary, this study comprehensively uncovered that CRGs could be identified as potential prognostic and immunological biomarkers in LUAD. Our current research could provide a solid theoretical basis for LUAD survival research and clinical decision-making.

Aberrant brain topological organization and granger causality connectivity in Parkinson's disease with impulse control disorders.

Introduction: Impulse control disorders (ICDs) refer to the common neuropsychiatric complication of Parkinson's disease (PD). The white matter (WM) topological organization and its impact on brain networks remain to be established. Methods: A total of 17 PD patients with ICD (PD-ICD), 17 without ICD (PD-NICD), and 18 healthy controls (HCs) were recruited. Graph theoretic analyses and Granger causality analyses were combined to investigate WM topological organization and the directional connection patterns of key regions. Results: Compared to PD-NICD, ICD patients showed abnormal global properties, including decreased shortest path length (Lp) and increased global efficiency (Eg). Locally, the ICD group manifested abnormal nodal topological parameters predominantly in the left middle cingulate gyrus (MCG) and left superior cerebellum. Decreased directional connectivity from the left MCG to the right medial superior frontal gyrus was observed in the PD-ICD group. ICD severity was significantly correlated with Lp and Eg. Discussion: Our findings reflected that ICD patients had excessively optimized WM topological organization, abnormally strengthened nodal structure connections within the reward network, and aberrant causal connectivity in specific cortical- limbic circuits. We hypothesized that the aberrant reward and motor inhibition circuit could play a crucial role in the emergence of ICDs.

Malignant peritoneal mesothelioma presenting with bilateral hydronephrosis and renal insufficiency: a case report and literature review.

Introduction: Malignant peritoneal mesothelioma (MPM) is an extremely rare tumor with nonspecific clinical manifestations, making diagnosis challenging. Case presentation: Herein, we report a case of MPM with occult onset presenting with bilateral hydronephrosis and renal insufficiency. A 30-year-old man was admitted to the Urology Department because of recurrent bilateral lower back pain. The etiology was unclear after a series of laboratory tests, imaging examinations, bone marrow aspiration, renal puncture biopsy, ascites examination, ureteroscopy, and so on. Finally, MPM was diagnosed by laparoscopic exploration and biopsy. Moreover, during the course of the disease, the patient's bilateral ureters were compressed, and the obstruction could not be relieved after the placement of ordinary ureteral stents. Percutaneous nephrostomy or metal ureteral stenosis was appropriate in managing malignant ureteral obstruction as it could improve renal function. Conclusions: The onset of this case was insidious, and the diagnosis was difficult, with a poor prognosis. To date, only a handful of cases have been reported. We hope this case can provide some enlightenment for our clinical work.

miR-133a and miR-135a Regulate All-Trans Retinoic Acid-Mediated Differentiation in Pediatric Acute Myeloid Leukemia by Inhibiting CDX2 Translation and Serve as Prognostic Biomarkers.

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML.

Nicotinamide riboside alleviates brain dysfunction induced by chronic cerebral hypoperfusion via protecting mitochondria.

Chronic cerebral hypoperfusion (CCH) is an enduring inadequate blood flow to the brain, resulting in vascular dementia (VaD). However, the effective treatment strategies are lacking. Supplementing with nicotinamide adenine dinucleotide (NAD+) has shown neuroprotective benefits in other neurodegenerative disorders. Nicotinamide riboside (NR), as a precursor of NAD+, is believed to hold promise in improving mitochondrial health, autophagy, and cognitive function. Meanwhile, NR has unique oral bioavailability, good tolerability, and minimal side effects, and it is the most promising for clinical translation. However, the effectiveness of NR in treating CCH-related VaD is still uncertain. The present study examined the neuroprotective effects of NR supplementation and its underlying mechanisms in a CCH rat model. The rats with CCH were given NR at a daily dosage of 400 mg/kg for 3 months. NR supplementation increased blood and brain NAD+ levels and improved brain function in CCH rats, including cognitive function and oxygenation capacity. It also reduced hippocampal neuronal loss and abnormalities and mitigated the decrease in dendritic spine density. The analysis of RNA sequencing in hippocampal tissue supports these findings. Electron microscopy and protein detection results suggest that NR may maintain mitochondrial structural integrity and exert a protective role by attenuating mitochondrial fission and impaired autophagy flux caused by CCH. In conclusion, these findings offer evidence for the neuroprotective potential of NR supplementation in ameliorating cognitive impairment induced by CCH.

Spectroscopy and Photochemistry of [Al, N, C, O, H]: Connectivity to Aluminium-Bearing Species in the Universe.

Aluminium is one of the most abundant metals in the universe and impacts the evolution of various astrophysical environments. Currently detected Al-bearing molecules represent only a small fraction of the aluminium budget, suggesting that aluminium may reside in other species. AlO and AlOH molecules are abundant in the oxygen-rich supergiant stars such as VY Canis Majoris, a stellar molecular factory with 60+ molecules including the prebiotic NC-bearing species. Additional Al-bearing molecules with N, C, O, and H may form in O-rich environments with radiation-accelerated chemistry. Here, we present spectroscopic identification of novel aluminium-bearing molecules composed of [Al, N, C, O, H] and [Al, N, C, O] from the reactions of Al atoms and HNCO in solid argon matrix, which are potential Al-bearing molecules in space. Photoinduced transformations among six [Al, N, C, O, H] isomers and three [Al, N, C, O] isomers, along with their dissociation reactions forming the known interstellar species, have been disclosed. These results provide new insight into the chemical network of astronomically detected Al-bearing species in space.

Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Objective: Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. Methods: To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Results: Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Conclusion: Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

Recurrent neural network for predicting absence of heterozygosity from low pass WGS with ultra-low depth.

BACKGROUND: The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). RESULTS: Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. CONCLUSIONS: Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.

Transcriptome analysis of adipose tissue and muscle of Laiwu and Duroc pigs.

Fat content is an important trait in pig production. Adipose tissue and muscle are important sites for fat deposition and affect production efficiency and quality. To regulate the fat content in these tissues, we need to understand the mechanisms behind fat deposition. Laiwu pigs, a Chinese indigenous breed, have significantly higher fat content in both adipose tissue and muscle than commercial breeds such as Duroc. In this study, we analyzed the transcriptomes in adipose tissue and muscle of 21-d-old Laiwu and Duroc piglets. Results showed that there were 828 and 671 differentially expressed genes (DEG) in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), respectively. Functional enrichment analysis showed that these DEG were enriched in metabolic pathways, especially carbohydrate and lipid metabolism. Additionally, in the longissimus muscle (LM) and psoas muscle (PM), 312 and 335 DEG were identified, demonstrating enrichment in the cell cycle and metabolic pathways. The protein-protein interaction (PPI) networks of these DEG were analyzed and potential hub genes were identified, such as FBP1 and SCD in adipose tissues and RRM2 and GADL1 in muscles. Meanwhile, results showed that there were common DEG between adipose tissue and muscle, such as LDHB, THRSP, and DGAT2. These findings showed that there are significant differences in the transcriptomes of the adipose tissue and muscle between Laiwu and Duroc piglets (P < 0.05), especially in metabolic patterns. This insight serves to advance our comprehensive understanding of metabolic regulation in these tissues and provide targets for fat content regulation.

An Antibacterial, Conductive Nanocomposite Hydrogel Coupled with Electrical Stimulation for Accelerated Wound Healing.

Background: Electrical stimulation (ES) can effectively promote skin wound healing; however, single-electrode-based ES strategies are difficult to cover the entire wound area, and the effectiveness of ES is often limited by the inconsistent mechanical properties of the electrode and wound tissue. The above factors may lead to ES treatment is not ideal. Methods: A multifunctional conductive hydrogel dressing containing methacrylated gelatin (GelMA), Ti3C2 and collagen binding antimicrobial peptides (V-Os) was developed to improve wound management. Ti3C2 was selected as the electrode component due to its excellent electrical conductivity, the modified antimicrobial peptide V-Os could replace traditional antibiotics to suppress bacterial infections, and GelMA hydrogel was used due to its clinical applicability in wound healing. Results: The results showed that this new hydrogel dressing (GelMA@Ti3C2/V-Os) not only has excellent electrical conductivity and biocompatibility but also has a durable and efficient bactericidal effect. The modified antimicrobial peptides V-Os used were able to bind more closely to GelMA hydrogel to exert long-lasting antibacterial effects. The results of cell experiment showed that the GelMA@Ti3C2/V-Os hydrogel dressing could enhance the effect of current stimulation and significantly improve the migration, proliferation and tissue repair related genes expression of fibroblasts. In vitro experiments results showed that under ES, GelMA@Ti3C2/V-Os hydrogel dressing could promote re-epithelialization, enhance angiogenesis, mediate immune response and prevent wound infection. Conclusion: This multifunctional nanocomposite hydrogel could provide new strategies for promoting infectious wound healing.

Motoric cognitive risk syndrome as a predictor of adverse health outcomes: A systematic review and meta-analysis.

INTRODUCTION: Motoric cognitive risk syndrome (MCR) is a newly proposed pre-dementia syndrome characterized by subjective cognitive complaints (SCC) and slow gait (SG). Increasing evidence links MCR to several adverse health outcomes, but the specific relationship between MCR and the risk of frailty, Alzheimer's disease (AD) and vascular dementia (VaD) remains unclear. Additionally, literature lacks analysis of MCR's components and associated health outcomes, complicating risk identification. This systematic review and meta-analysis aim to provide a comprehensive overview of MCR's predictive value for adverse health outcomes. METHODS: Relevant cross-sectional, cohort, and longitudinal studies examining the association between MCR and adverse health outcomes were extracted from seven electronic databases. The Newcastle Ottawa Scale (NOS) and modified NOS were used to assess the risk of bias in studies included in the analysis. Relative ratios (RRs) and 95% confidence intervals (CIs) were pooled for outcomes associated with MCR. RESULTS: Twenty-eight longitudinal or cohort studies and four cross-sectional studies with 1,224,569 participants were included in the final analysis. The risk of bias in all included studies was rated as low or moderate. Pooled analysis of RR indicated that MCR had a greater probability of increased the risk of dementia (adjusted RR=2.02; 95%CI=1.94-2.11), cognitive impairment (adjusted RR=1.72; 95%CI=1.49-1.99), falls (adjusted RR=1.32; 95%CI=1.17-1.50), mortality (adjusted RR=1.66; 95%CI=1.32-2.10); MCR had more prominent predictive efficacy for AD (adjusted RR=2.23; 95%CI=1.81-2.76) compared to VaD (adjusted RR=3.78; 95%CI=0.49-28.95), while excluding analyses from the study that utilized the Timed-up-and-go test and one-leg-standing to evaluate gait speed. One study examined the association between MCR and disability (HR=1.69; 95%CI=1.08-2.02) and frailty (OR=5.53; 95%CI=1.46-20.89). SG was a stronger predictor of the risk for dementia and falls than SCC (adjusted RR=1.22; 95%CI=1.11-1.34 vs. adjusted RR=1.19; 95%CI= 1.03-1.38). CONCLUSION: MCR increases the risk of developing any discussed adverse health outcomes and the predictive value for AD is superior to VaD. Additionally, SG is a stronger predictor of dementia and falls than SCC. Therefore, MCR should be routinely assessed among adults to prevent poor prognosis, and provide evidence to support future targeted interventions.

A Case of Clonorchiasis in a Non-endemic Region of China.

Clonorchiasis, an important foodborne parasitic disease, is prevalent in several Asian countries. In China, the three provinces with the highest incidence are Guangdong, Guangxi, and Heilongjiang, with no reported cases in Qingdao for nearly a decade. In this study, a 29-year-old male patient was diagnosed with fatty liver due to abnormal liver function during physical examination and was admitted to the hospital multiple times for examination and treatment within 3 years, but his liver function did not improve. Eventually, clonorchis eggs were found in the stool, confirming the diagnosis of clonorchiasis. The purpose of this report is to enhance the understanding of clonorchiasis among clinicians in no-prevalence areas, to familiarize laboratory technicians with egg identification, to strengthen parasite-knowledge training, and to reduce missed and misdiagnosed cases.

Associations between perceived and actual risk of HIV infection and HIV prevention services uptake among men who have sex with men in Shandong province, China: a cross-sectional study.

BACKGROUND: Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. METHODS: A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. RESULTS: A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 (P < 0.001). HIV testing uptake had a weak association with perceived high HIV prevalence among social networks (aOR = 1.156, post probability = 0.547). The perceived high HIV prevalence among national MSM was positive related to willingness to use PrEP (aOR = 1.903, post probability = 0.943) and PEP (aOR = 1.737, post probability = 0.829). Perceived personal risk (aOR = 4.486, post probability = 0.994) and perceived HIV prevalence among social networks (aOR = 1.280, post probability = 0.572) were related to history of using PrEP. Perceived personal risk (aOR = 3.144, post probability = 0.952), actual risk (aOR = 1.890, post probability = 0.950), and perceived risk among social networks (aOR = 1.502, post probability = 0.786) were related to history of using PEP. CONCLUSIONS: There is discordance between perceived and actual personal risk of HIV infection among MSM in China. HIV risk assessment and education on HIV prevalence among MSM should be strengthened to assist high-risk populations aware their risk accurately and hence access HIV prevention services proactively.

Role of the angiopoietin-like protein family in the progression of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease, with a range of conditions including non-alcoholic fatty liver, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Currently recognized as the liver component of the metabolic syndrome, NAFLD is intimately linked to metabolic diseases. Angiopoietin-like proteins (ANGPTLs) comprise a class of proteins that resemble angiopoietins structurally. It is closely related to obesity, insulin resistance and lipid metabolism, and may be the critical factor of metabolic syndrome. In recent years, many studies have found that there is a certain correlation between ANGPTLs and the occurrence and progression of NAFLD disease spectrum. This article reviews the possible mechanisms and roles of ANGPTL protein in the pathogenesis and progression of NAFLD.

Improvement of social functioning in patients with first-episode schizophrenia using blonanserin treatment: a prospective, multi-centre, single-arm clinical trial.

Objectives: This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. Methods: In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. Results: A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Conclusion: Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments.

Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy.

Radiotherapy (RT) is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors. In particular, immune responses triggered by RT, known as radio-immunotherapy, can partially inhibit the growth of distantly spreading tumors and recurrent tumors. However, the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immunogenicity of tumor. Herein, we report oxaliplatin (IV)-iron bimetallic nanoparticles (OXA/Fe NPs) as cascade sensitizing amplifiers for low-dose and robust radio-immunotherapy. The OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA (II) and Fe2+ in response to the reductive and acidic microenvironment within tumor cells. The cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage, increasing ROS and O2 levels, and amplifying the immunogenic cell death (ICD) effect after RT to facilitate potent immune activation. As a result, OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal effect. Moreover, a long-term immunological memory effect to protect mice from tumor rechallenging is observed. Overall, the bimetallic NPs-based cascade sensitizing amplifier system offers an efficient radio-immunotherapy regimen that addresses the key challenges.

Clinical application of metagenomic next-generation sequencing for the diagnosis of suspected infection in adults: A cross-sectional study.

Metagenomic next-generation sequencing (mNGS) has become an available method for pathogen detection. The clinical application of mNGS requires further evaluation. We conducted a cross-sectional study of 104 patients with suspected infection between May 2019 and May 2021. The risk factors associated with infection were analyzed using univariate logistic analysis. The diagnostic performance of pathogens was compared between mNGS and conventional microbiological tests. About 104 patients were assigned into 3 groups: infected group (n = 69), noninfected group (n = 20), and unknown group (n = 15). With the composite reference standard (combined results of all microbiological tests, radiological testing results, and a summary of the hospital stay of the patient) as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value of mNGS was 84.9%, 50.0%, 88.6%, and 42.1%, respectively. Compared with conventional microbiological tests, mNGS could detect more pathogens and had obvious advantages in Mycobacterium tuberculosis, Aspergillus, and virus detection. Moreover, mNGS had distinct benefits in detecting mixed infections. Bacteria-fungi-virus mixed infections were the most common in patients with severe pneumonia. mNGS had a higher sensitivity than conventional microbiological tests, especially for M. tuberculosis, Aspergillus, viruses, and mixed infections. We suggest that mNGS should be used more frequently in the early diagnosis of pathogens in critically ill patients in the future.