Antibiotic-Induced Gut Microbiota Dysbiosis Modulates Host Transcriptome and m6A Epitranscriptome via Bile Acid Metabolism.

Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6-methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.

A Novel Bifunctional Fusion Protein (Anti-IL-17A-sST2) Protects against Acute Liver Failure, Modulating the TLR4/MyD88 Pathway and NLRP3 Inflammasome Activation.

Acute liver failure (ALF) is a serious inflammatory disorder with high mortality rates, which poses a significant threat to human health. The IL-33/ST2 signal is a crucial regulator in inflammation responses associated with lipopolysaccharide (LPS)-induced macrophages. The IL-17A signaling pathway promotes the release of chemokines and inflammatory cytokines, recruiting neutrophils and T cells under LPS stimulation, thus facilitating inflammatory responses. Here, the potential therapeutic benefits of neutralizing the IL-17A signal and modulating the IL-33/ST2 signal in ALF were investigated. A novel dual-functional fusion protein, anti-IL-17A-sST2, was constructed, which displayed high purity and biological activities. The administration of anti-IL-17A-sST2 resulted in significant anti-inflammatory benefits in ALF mice, amelioration of hepatocyte necrosis and interstitial congestion, and reduction in TNF-α and IL-6. Furthermore, anti-IL-17A-sST2 injection downregulated the expression of TLR4 and NLRP3 as well as important molecules such as MyD88, caspase-1, and IL-1ß. The results suggest that anti-IL-17A-sST2 reduced the secretion of inflammatory factors, attenuated the inflammatory response, and protected hepatic function by regulating the TLR4/MyD88 pathway and inhibiting the NLRP3 inflammasome, providing a new therapeutic approach for ALF.

Study on the impact of COVID-19 pandemic on the mental health of Chinese college students: a cross-sectional analysis.

Background: The COVID-19 pandemic has significantly impacted the mental health of college students, prompting the need for universities to implement measures to mitigate these adverse effects. This study aims to assess the mental health status and mitigation measures of college students, identify the primary factors contributing to their mental health challenges, and provide suggestions for educational institutions to reduce negative psychological impacts. Methods: In February 2023, a questionnaire survey was conducted among 1,445 college students. Statistical analysis was performed on the survey results, and multiple regression models were used to identify significant influencing factors and optimize the model. Results: The study revealed correlations between factors affecting mental health during the pandemic, with interactions observed among some factors. Significant differences in mental health status were found among different groups of college students based on their information-sharing habits through apps and engagement in thesis research. Multiple regression analysis indicated that conducting academic research related to COVID-19 significantly increased the psychological stress of college students during the pandemic (p = 0.043). Among all mitigation measures, playing games demonstrated significant effectiveness in model analysis (p = 0.047). The optimization of the model showed that the multiple regression model considering the interaction of factors was more effective. Conclusion: Our research identifies crucial factors influencing the mental health of college students and investigates the mental health status of various student groups. We recommend that educational institutions adopt proactive strategies and a multifaceted approach to support the mental health of college students and address potential issues that may arise.

A potential strategy for bladder cancer treatment: inhibiting autophagy to enhance antitumor effects of Nectin-4-MMAE.

Research and development on Nectin-4 antibody-drug conjugates (ADC) have been greatly accelerated since the approval of enfortumab vedotin to treat uroepithelial cancer. During the course of this study, we identified that autophagy serves as a cytoprotective mechanism during Nectin-4-MMAE treatment and proposed a strategy to enhance the antitumor effects of Nectin-4-MMAE in bladder cancer. Nectin-4-MMAE rapidly internalized into bladder cancer cells in 30 minutes and released MMAE, inducing the onset of caspase-mediated apoptosis and leading to the inhibition of tumor cell growth. Transcriptomics showed significant alterations in autophagy-associated genes in bladder cancer cells treated with Nectin-4-MMAE, which suggested autophagy was activated by Nectin-4-MMAE. Furthermore, autophagy activation was characterized by ultrastructural analysis of autophagosome accumulation, immunofluorescence of autophagic flux, and immunoblotting autophagy marker proteins SQSTM1 and LC3 I/II. Importantly, inhibiting autophagy by LY294002 and chloroquine significantly enhances the cytotoxicity effects of Nectin-4-MMAE in bladder cancer cells. Additionally, we detected the participation of the AKT/mTOR signaling cascade in the induction of autophagy by Nectin-4-MMAE. The combination of Nectin-4-MMAE and an autophagy inhibitor demonstrated enhanced antitumor effects in the HT1376 xenograft tumor model. After receiving a single dose of Nectin-4-MMAE, the group that received the combination treatment showed a significant decrease in tumor size compared to the group that received only one type of treatment. Notably, one mouse in the combination treatment group achieved complete remission of the tumor. The combination group exhibited a notable rise in apoptosis and necrosis, as indicated by H&E staining and immunohistochemistry (cleaved caspase-3, ki67). These findings demonstrated the cytoprotective role of autophagy during Nectin-4-MMAE treatment and highlighted the potential of combining Nectin-4-MMAE with autophagy inhibitors for bladder cancer treatment.

CD80-Fc fusion protein as a potential cancer immunotherapy strategy.

The activation of T lymphocytes is a crucial component of the immune response, and the presence of CD80, a membrane antigen, is necessary for T-cell activation. CD80 is usually expressed on antigen-presenting cells (APCs), which can interact with cluster of differentiation 28 (CD28) or programmed cell death ligand 1 (PD-L1) to promote T-cell proliferation, differentiation and function by activating costimulatory signal or blocking inhibitory signal. Simultaneously, CD80 on the APCs also interacts with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells to suppress the response of specific effector T cells, particularly in the context of persistent antigenic stimulation. Due to the pivotal role of CD80 in the immune response, the CD80-Fc fusion protein has emerged as a promising approach for cancer immunotherapy. This review primarily focused on the crucial role of CD80 in the cancer immunotherapy. We also reviewed the current advancements in the research of CD80-Fc fusion proteins. Finally, we deliberated on the challenges encountered by CD80-Fc fusion proteins and proposed the potential strategies that could yield the benefits for patients.

Fundamental properties and phosphorus transformation mechanism of soybean straw during microwave hydrothermal conversion process.

Microwave hydrothermal (MHT) conversion is emerging as a promising technology for the disposal and reutilization of biowastes. This study investigated the fundamental properties and phosphorus transformation mechanism of soybean straw during the MHT conversion process. The oxygen-containing functional groups in soybean straw were stripped, and a trend of dehydration was observed as the temperature increased during the MHT process. Cellulose was identified as the major component of the MHT solid products at high temperature. Glucose and glucuronic acid in the MHT liquid products were gradually converted to formic acid and acetic acid with increasing temperature and holding time. The characteristics of the MHT products directly affected the changes in P speciation and transformation. Most of the P was distributed in liquid products and the impact of holding time was not significant on P distribution at low MHT temperature. With the increase in temperature and holding time, P gradually transferred into the solid products. The proportion of organic phosphorus and soluble inorganic phosphorus in soybean straw was high, and it decreased noticeably after the MHT process. The increase in MHT temperature promoted the conversion of OP and AP into IP and NAIP respectively. P K-edge X-ray absorption near edge structure analysis reveals that Ca5(PO4)3(OH) was the major component of soybean straw and more Ca5(PO4)3(OH) was formed at lower MHT temperature. This study provides fundamental knowledge on the property changes of soybean straw and the transformation of phosphorus during MHT conversion process, which is essential for its disposal and further utilization.

CMAUP database update 2024: extended functional and association information of useful plants for biomedical research.

Knowledge of the collective activities of individual plants together with the derived clinical effects and targeted disease associations is useful for plant-based biomedical research. To provide the information in complement to the established databases, we introduced a major update of CMAUP database, previously featured in NAR. This update includes (i) human transcriptomic changes overlapping with 1152 targets of 5765 individual plants, covering 74 diseases from 20 027 patient samples; (ii) clinical information for 185 individual plants in 691 clinical trials; (iii) drug development information for 4694 drug-producing plants with metabolites developed into approved or clinical trial drugs; (iv) plant and human disease associations (428 737 associations by target, 220 935 reversion of transcriptomic changes, 764 and 154121 associations by clinical trials of individual plants and plant ingredients); (v) the location of individual plants in the phylogenetic tree for navigating taxonomic neighbors, (vi) DNA barcodes of 3949 plants, (vii) predicted human oral bioavailability of plant ingredients by the established SwissADME and HobPre algorithm, (viii) 21-107% increase of CMAUP data over the previous version to cover 60 222 chemical ingredients, 7865 plants, 758 targets, 1399 diseases, 238 KEGG human pathways, 3013 gene ontologies and 1203 disease ontologies. CMAUP update version is freely accessible at https://bidd.group/CMAUP/index.html.

Inhibition of Hedgehog signaling ameliorates foam cell formation by promoting autophagy in early atherosclerosis.

Macrophages are the origin of most foam cells in the early stage of atherosclerotic plaques. However, the mechanism involved in the formation of macrophage-derived foam cell formation remains unclear. Here, we revealed that the hedgehog (Hh) signaling is critical in autophagy-lysosome pathway regulation and macrophage-derived foam cell formation. Inhibition of Hh signaling by vismodegib ameliorated lipid deposition and oxidative stress level in atherosclerotic plaques in high-fat diet-fed apoE-/- mice. For mechanistic study, how the Hh signaling modulate the process of foam cell formation were accessed afterward. Unexpectedly, we found that suppression of Hh signaling in apoE-/- mice had no significant impact on circulating cholesterol levels, indicating that Hh pathway modulate the procession of atherosclerotic plaque not through a traditional lipid-lowing mechanism. Instead, vismodegib was found to accelerate autophagosomes maturation as well as cholesterol efflux in macrophage-derived foam cell and in turn improve foam cell formation, while autophagy inhibitors (LY294002 or CQ) administration significantly attenuated vismodegib-induced cholesterol efflux and reversed the effect on foam cell formation. Therefore, our result demonstrated that inhibition of the Hh signaling pathway increases cholesterol efflux and ameliorates macrophage-derived foam cell formation by promoting autophagy in vitro. Our data thus suggested a novel therapeutic target of atherosclerosis and indicated the potential of vismodegib to treat atherosclerosis.

A collagen-binding SIRPαFc fusion protein for targeted cancer immunotherapy.

Collagen is abundant but exposed in tumor due to the abnormal tumor blood vessels, thus is considered as a tumor-specific target. The A3 domain of von Willebrand factor (vWF A3) is a kind of collagen-binding domain (CBD) which could bind collagen specifically. Previously we reported a chemosynthetic CBD-SIRPαFc conjugate, which could block CD47 and derived tumor-targeting ability by CBD. CBD-SIRPαFc conjugate represented improved anti-tumor efficacy with increased MHC II+ M1 macrophages, but the uncertain coupling ratio remained a problem. Herein, we produced a vWF A3-SIRPαFc fusion protein through eukaryotic expression system. It was examined at both molecular and cellular levels with its collagen affinity, uninfluenced original affinity to targets and phagocytosis-promoting function compared to unmodified SIRPαFc. Living imaging showed that vWF A3-SIRPαFc fusion protein derived the improved accumulation and retention in tumor than SIRPαFc. In the MC38 allograft model, vWF A3-SIRPαFc demonstrated a superior tumor-suppressing effect, characterized by increased MHC II+ M1 macrophages and T cells (particularly CD4+ T cells). These results revealed that vWF A3-SIRPαFc fusion protein derived tumor-targeting ability, leading to improved anti-tumor immunotherapeutic efficacy compared to SIRPαFc. Altogether, vWF A3 improved the anti-tumor efficacy and immune-activating function of SIRPαFc, supporting targeting tumor collagen as a possible targeted strategy.

A nomogram for predicting the risk of new vertebral compression fracture after percutaneous kyphoplasty.

BACKGROUND: New vertebral compression fractures (NVCFs) are common adverse events in percutaneous kyphoplasty (PKP). The present study aimed to investigate the risk factors for NVCFs in patients after PKP and to construct a nomogram for the prediction of the risk of re-fracture. METHODS: We retrospectively analyzed the medical records of patients after PKP surgery between January 2017 and December 2020. Patients were divided into an NVCF group (n = 225) and a control group (n = 94) based on the presence or absence of NVCFs, respectively, at follow-up within 2 years after surgery. Lasso regression was used to screen for risk factors for re-fracture. Based on the results, a Lasso-logistic regression model was developed, and its prediction performance was evaluated using receiver operating characteristic curves, calibration, and decision curve analysis. The model was visualized, and a nomogram was constructed. RESULTS: A total of eight potential predictors were obtained from Lasso screening. Advanced age, low body mass index, low bone mineral density, lack of anti-osteoporosis treatment, low preoperative vertebral body height, vertebral body height recovery ≥ 2, cement leakage, and shape D (lack of simultaneous contact of bone cement with the upper and lower plates) were included in the logistic regression model. CONCLUSIONS: A nomogram for predicting postoperative NVCF in PKP was developed and validated. This model can be used for rational assessment of the magnitude of the risk of developing NVCFs after PKP, and can help orthopedic surgeons make clinical decisions aimed at reducing the occurrence of NVCFs.

Unlocking potential: clinical benefits of enlarging the nail bed explored through continuous W-shaped incisions.

PURPOSE: Nail bed atrophy, a common condition for which conservative treatments have limited efficacy, continues to present challenges in determining the optimal surgical intervention. This study introduces a novel technique for nail bed expansion. MATERIALS AND METHODS: A total of 34 patients with nail bed atrophy, selected between 2015 and 2020 (ChiCTR2000036232), were randomized into a control group (n = 17) and a surgical group (n = 17). While no specialized treatment was administered to the control group, the surgical group underwent continuous W-shaped incisions on the ventral side of the digits. RESULTS: Following a 12-month follow-up period, changes in nail bed height, width, area, esthetic satisfaction, pain levels, and tactile sensation were assessed in both groups. In the surgical group, the height, width, and area of the nail bed increased significantly by 1.50 ± 0.49 times, 1.16 ± 0.23 times, and 1.69 ± 0.60 times, respectively, compared to the preoperative measurements. The newly-formed nail plate exhibited improved esthetics, characterized by its smoothness and transparency, a marked improvement over the control group (p < 0.05). Furthermore, this surgical approach showed significant effects, regardless of whether it was applied to fingers or toes. CONCLUSION: The continuous W-shaped incision technique demonstrated substantial benefits and could be a practical therapeutic approach for nail bed enlargement.

Production of antifungal iturins from vegetable straw: A combined chemical-bacterial process.

A combined chemical-bacterial process was developed to convert vegetable straw waste to high value antifungal iturins. Straws from three widely cultivated vegetable (cucumber, tomato and pepper) were evaluated as feedstocks for iturin production. Microwave assisted hydrolysis with very dilute acid (0.2% w/w H2SO4) achieved efficient reducing sugar recovery. The high glucose concentration in non-detoxified hydrolysate from pepper straw facilitated the optimal growth of Bacillus amyloliquefaciens strain Cas02 and stimulated the production of iturin. The fermentation parameters were optimised to enhance the iturin production efficiency. The obtained fermentation extract was further purified using macroporous adsorption resin, resulting in an iturin-rich extract that exhibited strong antifungal activity against Alternaria alternata with an IC50 of 176.44 µg/mL. Each iturin homologue was identified using NMR. Overall, 1.58 g iturin-rich extract containing 164.06 mg/g iturins was obtained from 100 g pepper straw, illustrating the great potential of valorising pepper straw via this process.

Ulva prolifera polysaccharide enhances the root colonisation by Bacillus amyloliquefaciens strain Cas02.

The application of biocontrol agent is important for the sustainable development of agriculture. Unsuccessful or limited colonisation by plant growth-promoting rhizobacteria (PGPR) has become an important constraint factor for their commercial application. Here, we report that Ulva prolifera polysaccharide (UPP) promotes root colonisation by Bacillus amyloliquefaciens strain Cas02. UPP serves as an environmental signal for bacterial biofilm formation and its glucose residue is used as a carbon source for the synthesis of the exopolysaccharides and poly-gamma-glutamate present in biofilm matrix. Greenhouse experiments demonstrated that UPP could effectively enhance the root colonisation by Cas02 in both the bacterial population and survival time under natural semiarid soil conditions. Furthermore, the microbiome analysis also indicated the promoted colonisation by Cas02, as well as the improved bacterial rhizosphere community structure, after combined treatment of UPP and Cas02. This study provides a practical approach to improve the biocontrol agent with seaweed polysaccharides.

A bifunctional fusion protein protected against diabetic nephropathy by suppressing NLRP3 activation.

Diabetic nephropathy (DN), the principal pathogeny of end-stage renal disease (ESRD), is related to metabolic disorders, chronic inflammation, and oxidative stress. It was reported that high expression of interleukin-17A (IL-17A) was intimately related to the progression of DN, and targeting IL-17A exhibited regulating effects on inflammation and autoimmunity but had only limited impact on the oxidative stress damage in DN. Recent studies showed that interleukin-22 (IL-22) could inhibit mitochondrial damage and inflammatory response. Thus, the cytokine IL-22 was first fused to anti-IL-17A antibody for endowing the antibody with the anti-hyperglycemia and anti-inflammation activity. Our study demonstrated that the fusion molecule, anti-IL17A/IL22 fusion protein, could not only lead to the increase of M1 macrophages and the decrease of M2 macrophages, further improving the immune microenvironment, but also prevent the loss of mitochondrial membrane potential by reducing the production of ROS in murine DN model. In addition, the fusion protein could block TRAF6/NF-κB and AKT/ROS/TXNIP signaling pathways, further synergistically restraining the production of NLRP3, thus suppressing the inflammatory response and playing beneficial effect on slowing down the progression of DN. In conclusion, our findings demonstrated that the bifunctional IL-17A antibody and IL-22 fusion protein were of great benefit to DN, which highlighted a potential therapeutic strategy. KEY POINTS: • Anti-IL17A/IL22 fusion protein could improve the immune microenvironment and reduce the production of ROS. • Anti-IL17A/IL22 fusion protein could block TRAF6/NF-κB and AKT/ROS/TXNIP signaling pathways and then restrain the activation of NLRP3.

Targeting CD47 enhanced the antitumor immunity of PD-L1 blockade in B-cell lymphoma.

Background: Only a subset of B-cell lymphoma (BCL) patients can benefit from immune checkpoint inhibitors targeting PD-1/PD-L1. Materials & methods: In the A20 model, SIRPα-Fc and anti-PD-L1 were employed to target CD47 and PD-L1 simultaneously. Flow cytometry, immunofluorescence and quantitative polymerase chain reaction were used to unravel the potential mechanisms. Results: Simultaneously targeting CD47 and PD-L1 activated CD8+ T cells with an increased release of effector molecules. Furthermore, infiltration of F4/80+iNOS+ M1 macrophages was enhanced by the dual therapy. Conclusion: Anti-CD47 therapy could sensitize BCL tumors to anti-PD-L1 therapy in a CD8+ T-cell- and M1-macrophage-dependent manner by promoting cytotoxic lymphocyte infiltration, which may provide a potential strategy for BCL treatment by simultaneously targeting CD47 and PD-L1.

Immune checkpoint inhibitors targeting PD-1/PD-L1 have become effective agents for cancer treatment. However, only a minority of patients benefit from this treatment in the clinic because of the limited response rate. Targeting CD47/SIRPα restores macrophage function and improves the response of antitumor immunity. Here, combination immunotherapy targeting CD47/SIRPα and PD-1/PD-L1 was investigated to increase the response rate and antitumor effect of PD-L1 monotherapy in B-cell lymphoma (BCL). This study broadens the application of the combination therapy and provided a promising strategy for B-cell lymphoma treatment by simultaneous targeting of PD-1/PD-L1 and CD47/SIRPα axis.

NPASS database update 2023: quantitative natural product activity and species source database for biomedical research.

Quantitative activity and species source data of natural products (NPs) are important for drug discovery, medicinal plant research, and microbial investigations. Activity values of NPs against specific targets are useful for discovering targeted therapeutic agents and investigating the mechanism of medicinal plants. Composition/concentration values of NPs in individual species facilitate the assessments and investigations of the therapeutic quality of herbs and phenotypes of microbes. Here, we describe an update of the NPASS natural product activity and species source database previously featured in NAR. This update includes: (i) new data of ∼95 000 records of the composition/concentration values of ∼1 490 NPs/NP clusters in ∼390 species, (ii) extended data of activity values of ∼43 200 NPs against ∼7 700 targets (∼40% and ∼32% increase, respectively), (iii) extended data of ∼31 600 species sources of ∼94 400 NPs (∼26% and ∼32% increase, respectively), (iv) new species types of ∼440 co-cultured microbes and ∼420 engineered microbes, (v) new data of ∼66 600 NPs without experimental activity values but with estimated activity profiles from the established chemical similarity tool Chemical Checker, (vi) new data of the computed drug-likeness properties and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties for all NPs. NPASS update version is freely accessible at http://bidd.group/NPASS.

Simultaneous blockade of VEGF-B and IL-17A ameliorated diabetic kidney disease by reducing ectopic lipid deposition and alleviating inflammation response.

The pathogenesis of diabetic kidney disease (DKD) is complicated. Current clinical treatments fail to achieve satisfactory efficacy in the prevention of DKD progression, it urgently needs novel and effective treatment for DKD. In this study, we firstly demonstrated that renal lipid metabolism abnormality and inflammation significantly changed in DKD conditions by mining public transcriptomic data of DKD patient samples. KEGG analysis further exhibited the critical role of vascular endothelial growth factor B (VEGF-B) and interleukin 17A (IL-17A) signal pathways in DKD progression, indicating that VEGF-B and IL-17A might be the promising targets for DKD treatment. Then the potential of a novel combination therapy, anti-VEGF-B plus anti-IL-17A antibody, was evaluated for DKD treatment. Our results demonstrated that simultaneous blockade of VEGF-B and IL-17A signaling with their neutralizing antibodies alleviated renal damage and ameliorated renal function. The therapeutic effectiveness was not only related to the reduced lipid deposition especially the neutral lipids in kidney but also associated with the decreased inflammation response. Moreover, the therapy alleviated renal fibrosis by reducing collagen deposition and the expression of fibronectin and α-SMA in kidney tissues. RNA-seq analysis indicated that differential expression genes (DEGs) in db/db mice were significantly clustered into lipid metabolism, inflammation, fibrosis and DKD pathology-related pathways, and 181 of those DEGs were significantly reversed by the combinatory treatment, suggesting the underlying mechanism of administration of anti-VEGF-B and anti-IL-17A antibodies in DKD treatment. Taken together, this study identified that renal lipid metabolism abnormality and inflammation were critically involved in the progression of DKD, and simultaneous blockade of VEGF-B and IL-17A signaling represents a potential DKD therapeutic strategy.

Effect of exoskeleton manipulator on hand function rehabilitation for postburn patients.

PURPOSE: Patients with scar contracture deformities caused by hand burns were treated with an exoskeleton manipulator system, which was equipped with games to explore its clinical application value. METHODS: Twenty patients who were treated for post-burn scars of bilateral hands between October 2020 and June 2021 were selected (ChiCTR2000036232). The patients were divided into two groups: control, 10 patients (traditional outpatient treatment); and experimental, 10 patients (exoskeleton manipulator system treatment). We compared the change in the total active motion (TAM) value, grip strength, scar improvement, and postoperative pain improvement. RESULTS: After 3 months of rehabilitation training, the improvement of thumb TAM was 33.80 ± 11.38 ° in the experimental group and 23.2 ± 6.13 ° in the control group. With respect to the index finger TAM, the improvement in the experimental and control groups was 84.50 ± 30.96 ° and 54.80 ± 15.89 °, respectively. The middle finger TAM of the experimental and control groups improved by 86.75 ± 32.85 ° and 60.25 ± 17.97 °, respectively. However, improvement of grip strength, scar score, and pain score were similar between the two groups. CONCLUSIONS: The exoskeleton manipulator system has excellent effects in improving burned hand joint movement, which is suitable for hand burn patients and has beneficial clinical effects.Implications for rehabilitationExercise is an effective means to improve the hand function of burn patients.The application of mechanical devices in the rehabilitation of burned hands can effectively help patients exercise.The A5 Hand Function Training System is an exoskeleton mechanical device that can exercise the small joints of the hand. It assists patients in using different computer games during treatment.