Folic acid and S-adenosylmethionine reverse Homocysteine-induced Alzheimer's disease-like pathological changes in rat hippocampus by modulating PS1 and PP2A methylation levels.

BACKGROUND: Abnormally elevated homocysteine (Hcy) is recognized as a biomarker and risk factor for Alzheimer's disease (AD). However, the underlying mechanisms by which Hcy affects AD are still unclear. OBJECTIVES: This study aimed to elucidate the effects and mechanisms by which Hcy affects AD-like pathological changes in the hippocampus through in vivo and in vitro experiments, and to investigate whether folic acid (FA) and S-adenosylmethionine (SAM) supplementation could improve neurodegenerative injuries. METHODS: In vitro experiments hippocampal neurons of rat were treated with Hcy, FA or SAM for 24 h; while the hyperhomocysteinemia (HHcy) in Wistar rats was established by intraperitoneal injection of Hcy, and FA was added to feed. The expression of ß-amyloid (Aß), phosphorylated tau protein, presenilin 1 (PS1) at the protein level and the activity of protein phosphatase 2A (PP2A) were detected, the immunopositive cells for Aß and phosphorylated tau protein in the rat hippocampus were also evaluated by immunohistochemical staining. RESULTS: FA and SAM significantly repressed Hcy-induced AD-like pathological changes in the hippocampus, including the increased tau protein phosphorylation at Ser214, Ser396 and the expression of Aß42. In addition, Hcy-induced PS1 expression increased at the protein level and PP2A activity decreased, while FA and SAM were able to retard that. CONCLUSIONS: The increase in PS1 expression and decrease in PP2A activity may be the mechanisms underlying the Hcy-induced AD-like pathology. FA and SAM significantly repressed the Hcy-induced neurodegenerative injury by modulating PS1 and PP2A methylation levels.

Fire needle pretreatment with 5-aminolevulinic acid photodynamic therapy combined with low-dose isotretinoin in the treatment of severe refractory nodulocystic acne.

BACKGROUND: Nodulocystic acne is a severe form of acne, which is commonly treated with oral isotretinoin, hormones, or antibiotics. However, drug therapy often has some side effects and poor compliance. Fire needle combined with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a simple, effective, short-term treatment with few adverse reactions, which is expected to be an effective physiotherapy for nodulocystic acne. Moreover, the combination with isotretinoin can reduce the dosage of the drug, thereby reducing the side effects of isotretinoin. OBJECTIVES: To evaluate the safety and efficacy of fire-needle pretreated ALA-PDT combined with low-dose isotretinoin in the treatment of severe refractory nodulocystic acne. METHODS: This study reported 10 patients with refractory nodulocystic acne who received combined treatment. During the treatment period, all patients received a low dose of oral isotretinoin capsules daily. The acne lesions were pretreated with fire needle before ALA-PDT treatment. The number of acne lesions, including papules, pustules, and nodular cysts, was documented at weeks 0, 2, 4, 8, and 12 to assess the therapeutic efficacy. Concurrently, adverse reactions such as pain, pruritus, and pigmentation changes were recorded and evaluated throughout the treatment course. RESULTS: After combined treatment, all patients achieved good therapeutic effects, with an overall effective rate of 90 % at week 12. After treatment, skin lesions such as nodules, and cysts subsided significantly. The combination therapy has no serious adverse effects and has a favorable safety profile. CONCLUSION: Fire needle pretreatment ALA-PDT combined with low-dose isotretinoin is effective and safe in the treatment of severe refractory nodular cystic acne, which is worthy of clinical promotion and research.

Screening and Analysis of SARS-CoV-2 Antibody Among Unvaccinated Blood Donors in Chongqing, China.

OBJECTIVE: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody among unvaccinated voluntary blood donors in Chongqing, and to provide evidence for epidemic surveillance. METHODS: A total of 10,208 voluntary blood donors from January 5 to January 20, 2021, in the Chongqing area were collected, and the SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies were detected by chemiluminescence, and the differences of antibody-positive rate in different gender, age, ABO blood group, and different risk areas were analyzed. RESULTS: Among 10208 blood donors, 10 were found to be positive for SARS-COV-2 IgG antibody, giving a positivity rate of SARS-COV-2 IgG at 0.10%, and 29 were positive for SARS-CoV-2 IgM antibody, with a positivity rate of SARS-CoV-2 IgM at 0.28%. There was no statistical difference in the positive rate of antibody among different genders, ages, and ABO blood types, but it was related to the number of confirmed coronavirus disease 2019 (COVID-19) cases in each city. CONCLUSIONS: The SARS-CoV-2 seroprevalence rate in Chongqing was low and correlated with the number of confirmed COVID-19 cases.

Bone mesenchymal stem cells improve cholestatic liver fibrosis by targeting ULK1 to regulate autophagy through PI3K/AKT/mTOR pathway.

Cholestatic liver disease (CLD) is a severe disease, which can progress to liver cirrhosis, even liver cancer. Hepatic stellate cells (HSCs) activation plays a crucial role in CLD development. Bone mesenchymal stem cells (BMSCs) treatment was demonstrated to be beneficial in liver diseases. However, the therapeutic effect and mechanism of BMSCs on CLD are poorly known. In the present study, we investigated the therapeutic effects and underlying mechanisms of BMSCs transplantation in mouse models of bile duct ligation-induced cholestatic liver fibrosis (CLF). The results revealed that BMSCs significantly improved liver function and reduced the formation of fibrosis after portal vein transplantation. Mechanistically, after coculturing BMSCs and HSCs, we identified that BMSCs alleviated starvation-induced HSCs activation. Further, BMSCs inhibited HSCs activation by decreasing autophagy, and PI3K/AKT/mTOR pathway was involved in the regulation. More importantly, ULK1 is identified as the main autophagy-related gene regulated by BMSCs in HSCs autophagy. Overexpression of ULK1 reversed the suppression of HSCs autophagy by BMSCs. Collectively, our results provide a theoretical basis for BMSCs targeting ULK1 to attenuate HSCs autophagy and activation and suggest that BMSCs or ULK1 may be an alternative therapeutic approach/target for the treatment of CLF.

Occupational daily walking steps have inverse relationship with papillary thyroid cancer risk and progression: a retrospective analysis.

OBJECTIVES: Investigate the impact of daily occupational walking steps on the progression of papillary thyroid cancer (PTC), a topic hitherto underresearched. MATERIAL AND METHODS: The authors analyzed the data from 800 individuals with PTC across stages 0-IV. Participants were evenly divided into 2 distinct occupational groups: office workers and construction workers (N = 400 each). Data included comprehensive records of daily walking steps, demographic information, and clinical indicators. Pearson's correlation coefficients or analysis of variance (ANOVA) were employed to assess the linkage between daily walking steps and PTC risk and stage, as well as associated biochemical markers. RESULTS: The analysis revealed a significant inverse relationship between daily walking steps and PTC risk. A higher frequency of daily steps was associated with reduced chances of PTC onset and a lower diagnostic stage of the disease. This protective effect of physical activity was particularly pronounced in the construc- tion worker cohort. Subsequent evaluations showed that construction workers who consistently logged higher daily steps had markedly lower levels of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, thyroid peroxidase antibody, thyroglobulin antibody, and thy- roglobulin (Tg). Notably, daily walking steps exhibited a strong inverse correlation with body mass index (BMI), age, PTC volumes, and levels of TSH and Tg across both occupational groups (ρ < -0.37). The increase in daily steps was associated with the reduction in PTC stages (p < 0.001). CONCLUSIONS: The research underscores the potential benefits of increased daily walking steps, suggesting that they may play a protective role in reducing PTC risk and moderating its progression. Int J Occup Med Environ Health. 2024;37(1):58-71.

Continuation of immunotherapy beyond progression is beneficial to the survival of advanced non-small-cell lung cancer.

PURPOSE: To investigate the potential clinical importance of continuing immunotherapy beyond progression in patients with advanced non-small-cell lung cancer (aNSCLC). METHODS: The data of patients with aNSCLC who experienced progressive disease after receiving first-line immunotherapy plus chemotherapy were collected from multiple centers for the period from January 1, 2018 to May 31, 2022. According to the second-line treatment, the patients were classified into two groups: the continuation of immunotherapy beyond progression (CIBP) group and the discontinuation of immunotherapy beyond progression (DIBP) group. The efficacy and safety of the treatment were compared between the groups. RESULTS: Overall, data from 169 patients were analyzed; 93 patients were enrolled in the CIBP group and 76 patients were in the DIBP group. The median second-line progression-free survival was 5.5 months in the CIBP group, which for the DIBP group was 3.4 (p = 0.011). The median overall survival of the CIBP group was 13.3 months, whereas that of the DIBP group was 8.8 months (p = 0.031). The disease control rate of the CIBP group (79.57%) was observably higher than that of the DIBP group (64.47%; p = 0.028). Among patients who responded better (complete or partial response) to prior therapy, the median progression-free survival was 5.5 months and 3.3 months in the CIBP and DIBP groups respectively (p = 0.022), and the median overall survival was 14.8 months and 8.8 months in the CIBP and DIBP groups respectively (p = 0.046). CONCLUSIONS: Continuing immunotherapy as a second-line treatment could be beneficial to the survival of patients with aNSCLC with disease progression beyond initial chemotherapy combined with immunotherapy.

[Prediction of quality markers and medicinal value of sea buckthorn leaves based on network pharmacology, content determination, and activity evaluation].

The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.

Influence of physicochemical changes and aggregation behavior induced by ultrasound irradiation on the antioxidant effect of highland barley ß-glucan.

The effect of ultrasonic treatment on the structure, morphology and antioxidant activity of highland barley ß-glucan (HBG) was investigated. Ultrasonic treatment for 30 min was demonstrated to improve the aqueous solubility of HBG, leading to a decrease in turbidity. Meanwhile, moderate ultrasound was found to obviously reduce the particle size distribution of HBG, and transform the entangled HBG molecules into flexible and extended chains, which reaggregated to form larger aggregates under long-time ultrasonication. The in vitro antioxidant capacity of HBG treated by ultrasonic first increased and then decreased compared to native HBG. Congo red complexation analysis indicated the existence of helix structure in HBG, which was untwisted after ultrasonic treatment. Furthermore, ultrasound treatment influenced the glucopyranose on HBG, which weakened the intramolecular hydrogen bond of HBG. The microscopic morphology showed that the spherical aggregates in native HBG solution were disaggregated and the untangled HBG chains reaggregated with excessive ultrasonication.

Ellagic Acid from Hull Blackberries: Extraction, Purification, and Potential Anticancer Activity.

Ellagic acid (EA) is present at relatively high concentrations in many berries and has many beneficial health effects, including anticancer properties. To improve the development and utilization of blackberry fruit nutrients, we divided Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW. Single-factor tests and response surface methodology were used to optimize the extraction process, while macroporous resin adsorption and alkali dissolution, acid precipitation, and solvent recrystallization were used for purification. The highest purity of the final EA powder was 90%. The anticancer assessment results determined by MTT assay showed that EA inhibited HeLa cells with an IC50 of 35 µg/mL, and the apoptosis rate of the cells increased in a dose-dependent manner, with the highest rate of about 67%. We evaluated the changes in the mRNA levels of genes related to the EA-mediated inhibition of cancer cell growth and initially verified the PI3K/PTEN/AKT/mTOR pathway as the pathway by which EA inhibits HeLa cell growth. We hope to provide a theoretical basis for the deep exploration and utilization of this functional food.

Quality control of Platycodon grandiflorum (Jacq.) A. DC. based on value chains and food chain analysis.

Platycodon grandiflorum (Jacq.) A. DC. has been proposed as a medicine and food homology, thus playing an important role in disease prevention and health promotion, with great potential for research and value in clinical application. We aimed to analyze stakeholders' production behavior and financial performance from a value chain (VC) perspective and provide a basis for improving the quality of P. grandiflorum and the interests of stakeholders. P. grandiflorum collected from different producing areas were chemically analyzed, and the quality of platycodin D was evaluated. Rstudio3.6.0 was used to analyze the correlation between total platycodins (as platycodin D, platycoside E, and platycodin D3) and platycodin D in P. grandiflorum, providing the basis for quality control of P. grandiflorum. In addition, we studied the anti-inflammatory and anti-cancer activities of P. grandiflorum extract under different links. Based on the food chain energy pyramid, the transfer efficiency of active components of P. grandiflorum in different links was studied. Accordingly, 10 different types of VCs were determined in producing P. grandiflorum. Our results show that vertical coordination has led to a more consistent traceability system and strict regulation of supply chains.

[Retracted] MicroRNA­15b promotes proliferation and invasion of non­small cell lung carcinoma cells by directly targeting TIMP2.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell migration and invasion images shown in Figs. 3B and D and 6C were strikingly similar to data that had already appeared in an article written by different authors at different research institutes [Liu C, Guan H, Wang Y, Chen M, Xu B, Zhang L, Lu K, Tao T and Zhang X: miR­195 inhibits EMT by targeting FGF2 in prostate cancer cells. PLoS One 9: e0144073, 2015]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 37: 3305­3312, 2017; DOI: 10.3892/or.2017.5604].

[Research progress on chemical constituents and pharmacological activities of Viola plants].

There are 500 species of Viola(Violaceae) worldwide, among which 111 species are widely distributed in China and have a long medicinal history and wide varieties. According to the authors' statistics, a total of 410 compounds have been isolated and identified from plants of this genus, including flavonoids, terpenoids, phenylpropanoids, organic acids, nitrogenous compounds, sterols, saccharides and their derivatives, volatile oils and cyclotides. The medicinal materials from these plants boast anti-microbial, anti-viral, anti-oxidant and anti-tumor activities. This study systematically reviewed the chemical constituents and pharmacological activities of Viola plants to provide a basis for further research and clinical application.

Phenolic compounds, antioxidant activity and sensory evaluation of sea buckthorn (Hippophae rhamnoides L.) leaf tea.

Sea buckthorn leaf tea, an emerging potential functional beverage product, has not yet had appropriate product standards and corresponding quality evaluation methods, and its poor taste directly affects the acceptance of the population, thus limiting its market consumption potential. In this study, two major packaging forms of sea buckthorn leaf tea available in the Chinese market were selected. The contents of total phenolics, total flavonoids, and 10 phenolic compounds, as well as the in vitro antioxidant capacity and sensory characteristics of sea buckthorn leaf tea were analyzed. Results showed that the quality of sea buckthorn leaf tea in the Chinese market varied widely. The total phenolic content, total flavonoid content, antioxidant activity, and consumer acceptance of bagged sea buckthorn leaf tea were higher than those of bulk sea buckthorn leaf tea. Multifactorial statistical analysis showed that the taste astringency of sea buckthorn leaf tea was closely related to ellagic acid and isorhamnetin-3-O-neohesperidin. Furthermore, isorhamnetin-3-O-neohesperidin had a greater effect on the antioxidant activity of sea buckthorn leaf tea. Therefore, ellagic acid and isorhamnetin-3-O-neohesperidin can be used as potential quality markers for sea buckthorn leaf tea. This work provides a reference for taste improvement and quality control of sea buckthorn leaf tea.

Cymbaria daurica L.: A Mongolian herbal medicine for treating eczema via natural killer cell-mediated cytotoxicity pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbaria daurica L. (C. daurica) is a perennial herb known commonly as "Xinba" (Chinese) and "Kanba-Arong" (Mongolian). In Mongolia, it is used as a traditional medicine to treat eczema and other skin diseases due to its anti-swelling, anti-inflammatory, anti-hemorrhagic, and anti-itching properties. However, the potential mechanism of action for eczema treatment has not been reported. AIM OF THE STUDY: To investigate the effect of C. daurica on 1-chloro-2,4-dinitrobenzene (DNCB)-induced eczema in rats and the associated action mechanism. MATERIALS AND METHODS: Qualitative analysis of C. daurica was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on information obtained from compound identification and relevant literature, the possible targets of C. daurica against eczema were analyzed using network pharmacology and molecular docking methods. The DNCB-induced eczema rat models were treated with different dosages of C. daurica extract (10, 50, and 250 mg/mL per day), and the therapeutic effects subsequently evaluated based on the degree of skin inflammation, spleen index, and hematoxylin and eosin staining (H&E staining). Enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative polymerase chain reaction (RT-qPCR), and western blotting were used to analyze the relevant target effects. The C. daurica mechanism of action on eczema was verified by animal experiments. High-performance liquid chromatography (HPLC) was carried out to determine the content of active ingredients in C. daurica. In addition, the physicochemical properties of the extract were evaluated. RESULTS: Our analysis of the 173 targets included in the protein-protein interaction (PPI) network identified tumor necrosis factor (TNF) and interleukin 2 (IL-2) as key targets involved in the treatment of eczema with C. daurica extract. Furthermore, the 173 targets were associated with the natural killer cell-mediated cytotoxicity pathway. Our results showed that C. daurica significantly reduced IL-2 and TNF-α serum levels in eczema rat models (P < 0.0001); thus, playing an important role in the anti-inflammatory response. Furthermore, according to the p-value, RT-qPCR and western blotting showed that the expression of Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), Vav guanine nucleotide exchange factor (Vav), and growth factor receptor-bound protein 2 (Grb2) changed in the skin of the eczema model rats after treatment with the C. daurica extract. CONCLUSION: Our study confirms that C. daurica can inhibit SHP-1, Vav, and Grb2 expression; thereby, inhibiting the natural killer cell-mediated cytotoxicity pathway. These results provide insight into the mechanism of C. daurica in treating eczema.

Three new compounds with their anti-glioma effects from the roots of Arnebia guttata Bunge.

Three new compounds, arneatas A-C (1-3), together with three known compounds (4-6) were isolated from the roots of Arnebia guttata Bunge. The structures were established on the basis of extensive spectroscopic data including NMR and HRESIMS. All the new compounds (1-3) were tested for their cytotoxic activity against two glioma cell lines (U118-MG and U373-MG) in vitro after treatment for 48 h. Compound 1 exhibited moderate cytotoxic activity against U118-MG and U373-MG glioma cell lines, with IC50 values of 10.4 and 17.5 µM, respectively.

Modification of Vancomycin Dosing in Cardiac Surgery With Cardiopulmonary Bypass.

This study aims to assess the risk factors for insufficient vancomycin concentrations for its prophylactic use in adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and to modify the dosing regimen to achieve appropriate plasma concentrations. A total of 27 patients with vancomycin dosing of 1 to 1.5 g based on a weight cutoff of 67 kg were included, of which only 13 (48.15%) had vancomycin plasma concentration >15 mg/L at surgical closure. Risk factors of vancomycin concentration <15 mg/L at surgical-site closure were confirmed by multivariate logistic regression analysis, which showed that CPB duration was an independent predictor. Patients with CPB duration >4 hours had significantly lower vancomycin concentrations and lower proportion in achieving target vancomycin concentration at the end of CPB and surgical closure. For patients with CPB >4 hours, the modified dosing regimen that a second dose of 0.5 to 0.75 g added at 4 hours since the onset of CPB improved the target achievement of vancomycin concentration at surgical closure. Taken together, CPB duration >4 hours was the risk factor for insufficient vancomycin concentration at surgical closure, while our modified dosing could improve the vancomycin concentrations for its prophylactic use in patients undergoing cardiac surgery with CPB.

Successful Treatment in a Child with Refractory Periungual Warts by Local Hyperthermia: A Case Report.

Periungual wart is a kind of verruca vulgaris that occurs alongside or underlying the nails, which is challenging to treat and prone to recurrence, seriously affecting the quality of patients' life. We report a 6-year-old boy with periungual warts who had experienced various treatments with no improvement and even worsening. Therefore, we tried to treat the patient with local hyperthermia which uses a patented device that has an infrared emission source. The heat generated by infrared rays acts on the local skin surface. The mechanism of this therapy may be to establish a specific immune response against human papillomavirus-infected tissues, thereby facilitating the clearance of human papillomavirus at irradiated and non-irradiated sites. Local hyperthermia has the advantages of non-contact, safety, noninvasive, less pain, and so on. After 5 treatments, the irradiated periungual warts completely cleared after 2 weeks. The unirradiated sites were almost cured after 7 weeks. This case suggests that local thermotherapy has shown great advantages in the treatment of these refractory periungual warts and offers a new and effective therapy in patients with periungual warts.

Bellidifolin from Gentianella acuta (Michx.) Hulten protects H9c2 cells from hydrogen peroxide-induced injury via the PI3K-Akt signal pathway.

Cardiovascular disease is the most common disease in the world and the first among the causes of human death. Its morbidity and mortality increase annually, but no effective treatment is available. Therefore, new drugs should be developed to treat cardiovascular disease. Gentianella acuta (Michx.) Hulten (G. acuta) is an important Mongolian medicine in China and elicits protective effects on cardiovascular health. In this study, liquid chromatography-mass spectrometry (LC-MS) combined with network pharmacology was used to screen the main active ingredients and confirm that bellidifolin was one of the main components for the treatment of ischemic heart disease. Then, rat myocardial (H9c2) cells injury model induced by hydrogen peroxide (H2O2) in vitro was established to verify the effect of bellidifolin on oxidative stress stimulation, including determination of antioxidant enzyme activity and apoptosis. Transcriptome sequencing, qRT-PCR, and western blot were performed to further verify the antioxidant stress mechanism of bellidifolin. Results showed that bellidifolin pretreatment decreased the rate of apoptosis and the levels of lactate dehydrogenase (LDH), creatine kinase (CK), and alanine aminotransferase (ALT). Conversely, it increased the contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in a dose-dependent manner, indicating that bellidifolin caused a protective effect on cardiomyocyte injury. Bellidifolin minimized the H2O2-induced cell injury by activating the PI3K-Akt signal pathway and downregulating glycogen synthase kinase-3ß (GSK-3ß) and p-Akt1/Akt1. Therefore, this work revealed that G. acuta has a good development prospect as an edible medicinal plant in cardiovascular disease. Its bellidifolin component is a potential therapeutic agent for cardiovascular disease induced by oxidative stress damage.

Integrated Physiological and Metabolomic Analyses Reveal the Differences in the Fruit Quality of the Blueberry Cultivated in Three Soilless Substrates.

With improving living standards, traditional blueberry planting modes cannot meet commercial demands, and blueberry cultivation with soilless substrate has become a popular solution in the blueberry industry. In this study, different soilless substrate treatments were found to markedly influence fruit appearance and intrinsic quality. The fruit in the 50:50 peat/pine bark (v/v) (FPB) treatment group had the maximum single fruit weight, largest vertical diameter, and brightest color, as well as the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) value, solid-acid ratio and anthocyanin content. The fruit in the 50:50 pine bark/rice husk (v/v) (FBR) treatment group had the highest total phenol and flavonoid levels, largest drip loss value, and lowest total pectin content and firmness value. Metabolomic analysis showed that flavonoid, carbohydrate, and carbohydrate conjugate, and amino acid, peptide, and analog levels were significantly different between groups. Fruit in the FPB group had the highest sucrose, D-fructose 1,6-bisphosphate, salidroside, tectorigenin, naringenin chalcone, trifolirhizin, and galangin contents. The increase in the relative expression of phenylalanine (Phe) promoted the synthesis of fruit polyphenols in the FBR group. Our results provide new insights into the effects of different substrates on the quality of blueberries and a reference for the soilless substrate cultivation of blueberries.