Irradiated engineered tumor cell-derived microparticles remodel the tumor immune microenvironment and enhance antitumor immunity.

Radiotherapy (RT), administered to roughly half of all cancer patients, occupies a crucial role in the landscape of cancer treatment. However, expanding the clinical indications of RT remains challenging. Inspired by the radiation-induced bystander effect (RIBE), we used the mediators of RIBE to mimic RT. Specifically, we discovered that irradiated tumor cell-released microparticles (RT-MPs) mediated the RIBE and had immune activation effects. To further boost the immune activation effect of RT-MPs to achieve cancer remission, even in advanced stages, we engineered RT-MPs with different cytokine and chemokine combinations by modifying their production method. After comparing the therapeutic effect of the engineered RT-MPs in vitro and in vivo, we demonstrated that tIL-15/tCCL19-RT-MPs effectively activated antitumor immune responses, significantly prolonged the survival of mice with malignant pleural effusion (MPE), and even achieved complete cancer remission. When tIL-15/tCCL19-RT-MPs were combined with PD-1 monoclonal antibody (mAb), a cure rate of up to 60% was achieved. This combination therapy relied on the activation of CD8+ T cells and macrophages, resulting in the inhibition of tumor growth and the establishment of immunological memory against tumor cells. Hence, our research may provide an alternative and promising strategy for cancers that are not amenable to conventional RT.

Induction of therapeutic immunity and cancer eradication through biofunctionalized liposome-like nanovesicles derived from irradiated-cancer cells.

Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an "eat me" signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.

Effect of GnRH Active Immunisation on Reproductive Performance of Male Sprague Dawley Rats.

To investigate the effect of active immunisation with gonadotropin-releasing hormone (GnRH) on the reproductive function in male Sprague Dawley (SD) rats, 24 42-day-old rats were randomly assigned to treatment with GnRH6-MAP, GnRH-OVA, a surgical castration group, and a blank control group. Each rat in the treatment groups was intramuscularly injected at 6, 8, and 10 weeks of age. The serum concentrations of testosterone (T), follicle-stimulating hormone (FSH), luteinising hormone (LH), and anti-GnRH antibodies were determined using enzyme-linked immunosorbent assays. The results showed that active immunisation with recombinant GnRH6-MBP and GnRH-OVA significantly increased the serum levels of anti-GnRH antibodies and reduced the serum concentrations of testosterone compared to the black control. Eight weeks after immunisation, the rats' testes were surgically removed for morphological evaluation, showing atrophy of the convoluted vasculature, relative emptying of the lumen, and insignificant differentiation of spermatogonial cells, which were increased in weight and volume compared with the blank control group. These findings indicated that active immunisation with GnRH can lead to testicular atrophy and reduce gonadal hormone concentrations, suggesting that GnRH is a highly effective immunogen.

The microRNA-7322-5p/p38/Hsp19 axis modulates Chilo suppressalis cell-defences against Cry1Ca: an effective target for a stacked transgenic rice approach.

Bacillus thuringiensis (Bt)-secreted crystal (Cry) toxins form oligomeric pores in host cell membranes and are a common element in generating insect-resistant transgenic crops. Although Cry toxin function has been well documented, cellular defences against pore-formation have not been as well developed. Elucidation of the processes underlying this defence, however, could contribute to the development of enhanced Bt crops. Here, we demonstrate that Cry1Ca-mediated downregulation of microRNA-7322-5p (miR-7322-5p), which binds to the 3' untranslated region of p38, negatively regulates the susceptibility of Chilo suppressalis to Cry1Ca. Moreover, Cry1Ca exposure enhanced phosphorylation of Hsp19, and hsp19 downregulation increased susceptibility to Cry1Ca. Further, Hsp19 phosphorylation occurs downstream of p38, and pull-down assays confirmed the interactions between Hsp19 and Cry1Ca, suggesting that activation of Hsp19 by the miR-7322-5p/p38/Hsp19 pathway promotes Cry1Ca sequestration. To assess the efficacy of targeting this pathway in planta, double-stranded RNA (dsRNA) targeting C. suppressalis p38 (dsp38) was introduced into a previously generated cry1Ca-expressing rice line (1CH1-2) to yield a single-copy cry1Ca/dsp38 rice line (p38-rice). Feeding on this rice line triggered a significant reduction in C. suppressalis p38 expression and the line was more resistant to C. suppressalis than 1CH1-2 in both short term (7-day) and continuous feeding bioassays as well as field trials. These findings provide new insights into invertebrate epithelium cellular defences and demonstrate a potential new pyramiding strategy for Bt crops.

MXene-Regulated Metal-Oxide Interfaces with Modified Intermediate Configurations Realizing Nearly 100% CO2 Electrocatalytic Conversion.

Electrocatalytic CO2 reduction via renewable electricity provides a sustainable way to produce valued chemicals, while it suffers from low activity and selectivity. Herein, we constructed a novel catalyst with unique Ti3 C2 Tx MXene-regulated Ag-ZnO interfaces, undercoordinated surface sites, as well as mesoporous nanostructures. The designed Ag-ZnO/Ti3 C2 Tx catalyst achieves an outstanding CO2 conversion performance of a nearly 100% CO Faraday efficiency with high partial current density of 22.59 mA cm-2 at -0.87 V versus reversible hydrogen electrode. The electronic donation of Ag and up-shifted d-band center relative to Fermi level within MXene-regulated Ag-ZnO interfaces contributes the high selectivity of CO. The CO2 conversion is highly correlated with the dominated linear-bonded CO intermediate confirmed by in situ infrared spectroscopy. This work enlightens the rational design of unique metal-oxide interfaces with the regulation of MXene for high-performance electrocatalysis beyond CO2 reduction.

Reprogramming the spleen into a functioning 'liver' in vivo.

OBJECTIVE: Liver regeneration remains one of the biggest clinical challenges. Here, we aim to transform the spleen into a liver-like organ via directly reprogramming the splenic fibroblasts into hepatocytes in vivo. DESIGN: In the mouse spleen, the number of fibroblasts was through silica particles (SiO2) stimulation, the expanded fibroblasts were converted to hepatocytes (iHeps) by lentiviral transfection of three key transcriptional factors (Foxa3, Gata4 and Hnf1a), and the iHeps were further expanded with tumour necrosis factor-α (TNF-α) and lentivirus-mediated expression of epidermal growth factor (EGF) and hepatocyte growth factor (HGF). RESULTS: SiO2 stimulation tripled the number of activated fibroblasts. Foxa3, Gata4 and Hnf1a converted SiO2-remodelled spleen fibroblasts into 2×106 functional iHeps in one spleen. TNF-α protein and lentivirus-mediated expression of EGF and HGF further enabled the total hepatocytes to expand to 8×106 per spleen. iHeps possessed hepatic functions-such as glycogen storage, lipid accumulation and drug metabolism-and performed fundamental liver functions to improve the survival rate of mice with 90% hepatectomy. CONCLUSION: Direct conversion of the spleen into a liver-like organ, without cell or tissue transplantation, establishes fundamental hepatic functions in mice, suggesting its potential value for the treatment of end-stage liver diseases.

Multi-parametric magnetic resonance imaging of liver regeneration in a standardized partial hepatectomy rat model.

BACKGROUND: We aimed to evaluate the correlation between the pathological changes and multi-parameter MRI characteristics of liver regeneration (LR) in a standard partial hepatectomy (PH) rat model. METHODS: Seventy Sprague-Dawley rats were randomly divided into two groups: MR scan group (n = 14) and pathologic analysis (PA) group (n = 56). All 14 rats in the MR group underwent liver T1 mapping, T2 mapping, and diffusion kurtosis imaging before and the 1st, 2nd, 3rd, 5th, 7th, 14th, and 21st day after 70% hepatectomy. Seven rats in the PA group were euthanized at each time point to determine Ki-67 indices, hepatocyte size (HTS), steatosis grade, and inflammation score. RESULTS: Liver T1 and T2 values increased to maximum on day 2 (P < 0.001 vs. baseline), D and K values decreased to minimum on day 3 and 2, respectively (P < 0.001 vs. baseline), then all parameters returned to baseline gradually. Hepatocyte Ki-67, hepatocyte size, steatosis grade, and inflammation score initially increased after surgery (P < 0.05 vs. baseline), followed by a gradual decline over time. Both T2 and K values correlated well with Ki-67 indices (r = 0.765 and - 0.807, respectively; both P < 0.001), inflammation (r = 0.809 and - 0.724, respectively; both P < 0.001), steatosis grade (r = 0.814 and - 0.725, respectively; both P < 0.001), and HTS (r = 0.830 and - 0.615, respectively; both P < 0.001). CONCLUSIONS: PH induced liver changes that can be observed on MRI. The MRI parameters correlate with the LR activity and allow monitoring of LR process.

Microparticles: biogenesis, characteristics and intervention therapy for cancers in preclinical and clinical research.

Extracellular vesicles (EVs), spherical biological vesicles, mainly contain nucleic acids, proteins, lipids and metabolites for biological information transfer between cells. Microparticles (MPs), a subtype of EVs, directly emerge from plasma membranes, and have gained interest in recent years. Specific cell stimulation conditions, such as ultraviolet and X-rays irradiation, can induce the release of MPs, which are endowed with unique antitumor functionalities, either for therapeutic vaccines or as direct antitumor agents. Moreover, the size of MPs (100-1000 nm) and their spherical structures surrounded by a lipid bilayer membrane allow MPs to function as delivery vectors for bioactive antitumor compounds, with favorable phamacokinetic behavior, immunostimulatory activity and biological function, without inherent carrier-specific toxic side effects. In this review, the mechanisms underlying MP biogenesis, factors that influence MP production, properties of MP membranes, size, composition and isolation methods of MPs are discussed. Additionally, the applications and mechanisms of action of MPs, as well as the main hurdles for their applications in cancer management, are introduced.

Nanoparticle facilitated stacked-dsRNA improves suppression of the Lepidoperan pest Chilo suppresallis.

BACKGROUND: In recent years, gene knockdown technology using double-stranded RNA (dsRNA) has been widely used as an environment-friendly pest control strategy, but its instability and limited cellular uptake have limited its overall effect. Studies have shown that the efficiency of single dsRNA can be improved by using various nanomaterials. However, the effect of stacked-dsRNA wrapped by nanomaterial on pests remains unclear. In the present study, both CYP15C1 and C-factor genes were cloned from the midgut of C. suppressalis, and the transcript of C-factor is most highly expressed in heads. Feeding a dsCYP15C1 or dsC-factor - nanomaterial mixture can downregulate the gene expression and significantly increase larval mortality. More importantly, feeding the stacked-dsRNA wrapped by nanomaterial can significantly increase the mortality of C. suppressalis, compared with feeding dsCYP15C1 or dsC-factor - nanomaterial mixture alone. These results showed that CYP15C1 and C-factor could be potential targets for an effective management of C. suppressalis, and we developed a nanoparticle-facilitated stacked-dsRNA strategy in the control of C. suppresallis. Our research provides a theoretical basis for gene function analysis and field pest control, and will promote the application of RNAi technology in the stacked style of pest control.

Electroactive Hydroxyapatite/Carbon Nanofiber Scaffolds for Osteogenic Differentiation of Human Adipose-Derived Stem Cells.

Traditional bone defect treatments are limited by an insufficient supply of autologous bone, the immune rejection of allogeneic bone grafts, and high medical costs. To address this medical need, bone tissue engineering has emerged as a promising option. Among the existing tissue engineering materials, the use of electroactive scaffolds has become a common strategy in bone repair. However, single-function electroactive scaffolds are not sufficient for scientific research or clinical application. On the other hand, multifunctional electroactive scaffolds are often complicated and expensive to prepare. Therefore, we propose a new tissue engineering strategy that optimizes the electrical properties and biocompatibility of carbon-based materials. Here, a hydroxyapatite/carbon nanofiber (HAp/CNF) scaffold with optimal electrical activity was prepared by electrospinning HAp nanoparticle-incorporated polyvinylidene fluoride (PVDF) and then carbonizing the fibers. Biochemical assessments of the markers of osteogenesis in human adipose-derived stem cells (h-ADSCs) cultured on HAp/CNF scaffolds demonstrate that the material promoted the osteogenic differentiation of h-ADSCs in the absence of an osteogenic factor. The results of this study show that electroactive carbon materials with a fibrous structure can promote the osteogenic differentiation of h-ADSCs, providing a new strategy for the preparation and application of carbon-based materials in bone tissue engineering.

Somatostatin neurons in the central amygdala mediate anxiety by disinhibition of the central sublenticular extended amygdala.

Fear and anxiety are two defensive emotional states evoked by threats in the environment. Fear can be initiated by either imminent or future threats, but experimentally, it is typically studied as a phasic response initiated by imminent danger that subsides when the threats is removed. In contrast, anxiety is a sustained response, initiated by imagined or potential threats. The central amygdala (CeA) is a key structure active during both fear and anxiety but thought to engage different neural systems. Fear responses are triggered by activation of somatostatin (SOM) expressing neurons in the lateral division of the CeA (CeL), and downstream projections from the medial division. Anxiety responses engage the central extended amygdala that includes the CeA, central sublenticular extended amygdala (SLEAc) and bed nucleus of the stria terminalis, but the nature of connections between these regions is not understood. Here using a combination of tract tracing, electrophysiology, and behavioral analysis in mice, we show that a population of SOM+ neurons in the CeL project to the SLEAc where they inhibit local GABAergic interneurons. Optogenetic activation of this input to the SLEAc has no effect on movement, but is anxiogenic in both open field and elevated plus maze. Our results define the inhibitory connections between CeL and SLEAc and establish a specific CeL to SLEAc projection as a circuit element in mediating anxiety.

Chlorinated Paraffins in Human Milk from Urban Sites in China, Sweden, and Norway.

Short-, medium-, and long-chain chlorinated paraffins (SCCPs, MCCPs, and LCCPs) were analyzed in human milk from the Yangtze River Delta (YRD) and Scandinavia. Individual samples were collected from Shanghai, Jiaxing, and Shaoxing (China), Stockholm (Sweden), and Bodø (Norway) between 2010 and 2016. Mean concentrations (range) of SCCPs, MCCPs, and LCCPs in samples from the YRD were 124 [

Knockdown of the aminopeptidase N genes decreases susceptibility of Chilo suppressalis larvae to Cry1Ab/Cry1Ac and Cry1Ca.

Bacillus thuringiensis (Bt) insecticide is currently the most widely used bioinsecticide. Bt expressing cry genes are some of the most successful foreign-genome-inserting genes used in transgenic insect-resistant crop development. Cry toxins are resistant to lepidopteran pests, such as Chilo suppressalis, a major insect pest of rice worldwide. Since Cry toxins exert their activity by binding to specific receptors in the midgut of target insects, identification of functional Cry toxin receptors in the midgut of C. suppressalis larvae is crucial to evaluate potential resistance mechanisms and develop effective strategies for inhibiting insect resistance. In this study, we isolated two aminopeptidase N genes (APN6 and APN8) from C. suppressalis and determined that they were expressed in the foregut. APN6 was highly expressed at the fourth instar, and APN8 was highly expressed in adult and pupa. Knockdown of CsAPN6 and CsAPN8 by RNA interference resulted in significantly decreased susceptibility of larvae to Bt rice varieties TT51 (expressing cry1Ac/cry1Ab fusion genes) and T1C-19 (expressing cry1Ca), but not T2A-1 (expressing cry2Aa). These findings suggest that both APN6 and APN8 are involved in the toxicity of Cry1Ac/Cry1Ab and Cry1Ca toxins.

Prognostic impact of tumor mutation burden and the mutation in KIAA1211 in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive lung cancer subtype with poor survival and limited treatment options. Sequencing results have revealed gene mutations associated with SCLC, however, the correlation between the genomic alterations and clinical prognosis of SCLC is yet unclear. METHODS: Targeted next-generation sequencing of 62 cancer related genes was performed on 53 SCLC samples. The correlations between clinical outcomes and genomic alterations were analyzed. RESULTS: 38/62 (61.3%) candidate genes harbored some alterations, while all the SCLC samples carried at least 3 gene mutations. The most common nonsynonymous mutations included ERBB2 (95.9%), CREBBP (95.9%), and TP53 (77.6%). The median nonsynonymous tumor mutation burden (TMB) was 21.7 mutations/Mb (rang, 9.3-55.9). High TMB (> 21 mutations/Mb) was good prognostic factor in overall survival (OS) (21.7 vs. 10.4 months, P = 0.012). Multivariate analysis showed that high TMB was an independent prognostic factor. The overall survival (OS) of patients carrying KIAA1211 mutation was significantly longer than those with wild-type KIAA1211 (P < 0.001). CONCLUSIONS: The current study highlights the potential role of genomic alterations for the prognosis of SCLC. Higher TMB was associated with a better prognosis, and KIAA1211 might be a good prognostic factor in SCLC.

Enhanced production of total flavones from Inonotus baumii by multiple strategies.

As one kind of important secondary metabolites produced by Inonotus baumii, flavones can be applied in food, medicine, and other industries due to their biological activities such as antioxidant, anticancer, and antibacterial activity. To enhance total flavone production in submerged fermentation of I. baumii, three different strategies, optimization of fermentation parameters by statistical designs including Plackett-Burman design and response surface methodology, addition of precursors and elicitors, and two-phase culture, were used. The production of total flavones (PTF) reached 1532.83 mg/L when the optimized medium was used. All precursors and elicitors can increase the PTF. The maximum PTF (2184.06 mg/L, up to 1.57-fold) was obtained with the addition of both AgNO3 and glutathione in fermentation media. Interestingly, when 0.5% (w/v) DM130 macroporous resin as adsorbent was added to fermentation broth on day 4 of culture, the highest production reached 2407.79 mg/L with this two-phase culture strategy. These methods can be further applied to large-scale industrial production and broaden the application of flavones.

Viral polymerase inhibitors T-705 and T-1105 are potential inhibitors of Zika virus replication.

Since 2015, 69 countries and territories have reported evidence of vector-borne Zika virus (ZIKV) transmission. Currently, there are no effective licensed vaccines or drugs available for the treatment or prevention of ZIKV infection. We tested a series of compounds for their ability to inhibit ZIKV replication in cell culture. The compounds in T-705 (favipiravir) and T-1105 were found to have antiviral activity, suggesting that these compounds are promising candidates for further development as specific antiviral drugs against ZIKV.

Purification and characterization of thermostable serine proteases encoded by the genes ttha0099 and ttha01320 from Thermus thermophilus HB8.

As an important class of proteases, serine proteases are required to show high activity under diverse conditions, especially at high temperatures. In the current study, two serine proteases SP348 and SP404 were analyzed by different bioinformatics tools. Both proteins are comprised of a trypsin domain and a PDZ domain, and belong to the trypsin family of proteases. The proteins were successfully expressed with Trx-tags as soluble proteins in the specialized Escherichia coli Rosetta-gami B(DE3)pLysS strain. A simple three-step purification protocol involving heat treatment, Ni-NTA purification and gel filtration was adopted to purify SP404. The molecular weight of recombinant SP404 was about 64 kDa. According to the circular dichroism spectroscopy analysis, SP404 is thermostable at 70 °C with alpha-helix, beta-sheet and random coil contents of about 8, 22 and 70 %, respectively. Our findings may broaden the range of microorganism-derived proteases and have a wide potential for industrial and fundamental studies.

Acetazolamide attenuates chemical-stimulated but not thermal-stimulated acute pain in mice.

AIM: Acetazolamide (AZA), a carbonic anhydrase (CA) inhibitor, has been found to alleviate inflammatory and neuropathic pain in rats. In the present study, we investigated the effects of AZA on thermal- and chemical-stimulated acute pain in mice and the possible mechanisms underlying the effects. METHODS: Five acute pain models based on thermal and chemical stimuli were established to investigate the effects of AZA on different types of nociception in mice. The antinociceptive effects of methazolamide (another CA inhibitor) and diazepam (a positive allosteric modulator of GABAA receptor) were also examined. The drugs were administered either intraperitoneally (ip) or intrathecally. RESULTS: AZA (50-200 mg/kg, ip) did not produce analgesia in two thermal-stimulated acute pain models, ie, mouse tail-flick and hot-plate tests. In contrast, AZA (50-200 mg/kg, ip) dose-dependently reduced paw licking time in both capsaicin and formalin tests in mice. A similar result was observed in a mouse acetic acid-induced writhing test. However, AZA (10 nmol/mouse, intrathecally) did not produce significant analgesia in the 3 chemical-stimulated acute pain models. In addition, methazolamide (50-200 mg/kg, ip) and diazepam (0.25-1.0 mg/kg, ip) did not produce significant analgesia in either thermal- or chemical-stimulated acute pain. CONCLUSION: AZA produces analgesia in chemical-stimulated, but not thermal-stimulated acute pain in mice. The attenuation of chemical-stimulated acute pain by AZA may not be due to enhancement of GABAA receptor-mediated inhibition via inhibiting CA activity but rather a peripheral ion channel-related mechanism.

ß-Indole-3-acetic acid attenuated collagen-induced arthritis through reducing the ubiquitination of Foxp3 via the AhR-TAZ-Tip60 pathway.

Massive evidence shows that intestinal tryptophan metabolites affected by intestinal flora can modulate the progression of rheumatoid arthritis (RA). However, the effects and mechanisms of intestinal tryptophan metabolites on RA are not yet detailed. Herein, we investigated the protective effects of intestinal tryptophan metabolites on RA and its detailed mechanisms. In this study, the collagen-induced arthritis (CIA) rat model was established. Based on metabolomics analysis, the contents of ß-indole-3-acetic acid (IAA), indolylpropionic acid, and indole-3-ß-acrylic acid in the sera of CIA rats were significantly less compared with those of the normal rats. Under the condition of Treg or Th17 cell differentiation, IAA significantly promoted the differentiation and activation of Treg cells instead of Th17 cells. Intestinal tryptophan metabolites are well-known endogenic ligands of aryl hydrocarbon receptor (AhR). Not surprisingly, IAA increased the level of Foxp3 through activating the AhR pathway. Interestingly, IAA had little impact on the level of Foxp3 mRNA, but reducing the ubiquitination and degradation of Foxp3. Mechanically, IAA reduced the expression of the transcriptional coactivator TAZ, which was almost completely reversed by either AhR antagonist CH223191 or siRNA. In vitro, IAA decreased the combination of TAZ and the histone acetyltransferase Tip60, while it increased the combination of Tip60 and Foxp3. In CIA rats, oral administration of IAA increased the number of Treg cells and relieved the inflammation. A combined use with CH223191 almost abolished the effect of IAA. Taken together, IAA attenuated CIA by promoting the differentiation of Treg cells through reducing the ubiquitination of Foxp3 via the AhR-TAZ-Tip60 pathway.

Intervention of computer-assisted cognitive training combined with occupational therapy in people with mild cognitive impairment: a randomized controlled trial.

Objective: Investigate the impact of combined computerized cognitive training and occupational therapy on individuals with mild cognitive impairment (MCI). Methods: We randomly assigned 118 MCI patients into two groups: a combined intervention group (n = 37) and a control group (n = 81), the latter receiving standard nursing care. The intervention group additionally underwent 12 weeks of computerized cognitive training and occupational therapy. Blind assessors evaluated cognitive performance, anxiety, depression, and daily living activities before the intervention, post-intervention, and at a 3-month follow-up. Results: Repeated-measures analysis of variance showed that the sMoCA scores, HAMA scores, and ADL scores of the experimental group at T2 (post-intervention) and T3 (3-month follow-up) were higher than those of the control group, and the difference was statistically significant (p < 0.001, p < 0.001, p = 0.026). Conclusion: Computerized cognitive training combined with occupational therapy can improve patients' cognitive status, enhance their compliance with continuing care, and maintain their anxiety and self-care ability at a stable level. Clinical trial registration: https://www.chictr.org.cn/index.html, identifier ChiCTR2200065014.