Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To investigate the effects of hyaluronic acid and proteoglycan-linked protein 1 (HAPLN1) secreted by synovial fibroblasts (FLS) on the polarization of macrophages (Mϕ) in rheumatoid arthritis (RA). Methods Human monocytic leukemia cells (THP-1) were differentiated into Mϕ, which were subsequently exposed to recombinant HAPLN1 (rHAPLN1). RA-FLS were transfected separately with HAPLN1 overexpression plasmid (HAPLN1^OE) or small interfering RNA targeting HAPLN1 (si-HAPLN1), and then co-cultured with Mϕ to establish a co-culture model. The viability of Mϕ was assessed using the CCK-8 assay, and the proportions of pro-inflammatory M1-type and anti-inflammatory M2-type Mϕ were analyzed by flow cytometry. Additionally, the expression levels of inflammatory markers, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS), were quantified using quantitative real-time PCR and Western blot analysis. Results The viability of Mϕ was increased in the rHAPLN1 group compared to the control group. Furthermore, both the M1/Mϕ ratio and inflammatory factor levels were elevated in the rHAPLN1 and HAPLN1^OE groups. In contrast, the si-HAPLN1 group exhibited a decrease in the M1/Mϕ ratio and inflammatory factor expression. Notably, the introduction of rHAPLN1 in rescue experiments further promoted Mϕ polarization towards the M1 phenotype. Conclusion HAPLN1, secreted by RA fibroblast-like synoviocytes (RA-FLS), enhances Mϕ polarization towards the M1 phenotype.
Humans ; Arthritis, Rheumatoid/genetics* ; Macrophages/immunology* ; Fibroblasts/metabolism* ; Phenotype ; Extracellular Matrix Proteins/genetics* ; Proteoglycans/genetics* ; Synovial Membrane/cytology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; Nitric Oxide Synthase Type II/genetics* ; Cell Differentiation ; Coculture Techniques ; THP-1 Cells

Motor imagery (MI) is a mental process that can be recognized by electroencephalography (EEG) without actual movement. It has significant research value and application potential in the field of brain-computer interface (BCI) technology. To address the challenges posed by the non-stationary nature and low signal-to-noise ratio of MI-EEG signals, this study proposed a Riemannian spatial filtering and domain adaptation (RSFDA) method for improving the accuracy and efficiency of cross-session MI-BCI classification tasks. The approach addressed the issue of inconsistent data distribution between source and target domains through a multi-module collaborative framework, which enhanced the generalization capability of cross-session MI-EEG classification models. Comparative experiments were conducted on three public datasets to evaluate RSFDA against eight existing methods in terms of classification accuracy and computational efficiency. The experimental results demonstrated that RSFDA achieved an average classification accuracy of 79.37%, outperforming the state-of-the-art deep learning method Tensor-CSPNet (76.46%) by 2.91% ( P < 0.01). Furthermore, the proposed method showed significantly lower computational costs, requiring only approximately 3 minutes of average training time compared to Tensor-CSPNet's 25 minutes, representing a reduction of 22 minutes. These findings indicate that the RSFDA method demonstrates superior performance in cross-session MI-EEG classification tasks by effectively balancing accuracy and efficiency. However, its applicability in complex transfer learning scenarios remains to be further investigated.
Electroencephalography/methods* ; Brain-Computer Interfaces ; Humans ; Imagination/physiology* ; Signal Processing, Computer-Assisted ; Movement/physiology* ; Signal-To-Noise Ratio ; Deep Learning ; Algorithms

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Three throat swab samples from infants and young children in Hubei Province were identified as positive for enteroviruses. All subjects were one month old, and the onset of symptoms occurred in June; these cases were sporadic and exhibited no clear epidemiological associations. The results of VP1 gene amplification analysis indicated that all three infant cases were attributed to Echovirus 30 (ECHO30). The ECHO30 strain isolated from the three samples was classified as Cluster Ⅲ within the H gene subtype. Whole genome amplification analysis revealed that the ECHO30 strain from Hubei exhibited the highest homology with ECHO30/MW586892/Ashburton/17WQ2027G/USA/2007-08-20 from GenBank, demonstrating nucleotide and amino acid homologies of 97.6% and 99.3%, respectively. Recombination analysis indicated the presence of recombination events in the non-structural protein region of the ECHO30 Hubei strain, with recombinant fragments potentially originating from ECHO30/KY888274/14-397/Germany/2013 and ECHO18 strains Echo18/MN815811/BJ2018-S6363/Beijing/2018. This study provides a comprehensive analysis of the genetic evolution of the ECHO30 strain prevalent in Hubei Province, contributing essential data for the prevention of ECHO30 infections.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

AIM To optimize the extraction process for Bletillae Rhizoma,and to evaluate its anti-oxidant,tyrosinase inhibitory activities.METHODS With ultrasound time,ethanol concentration and solid-liquid ratio as influencing factors,the total extraction content of gastrodin,protocatechualdehyde,p-hydroxybenzaldehyde,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate-2-glucoside,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate,yam Ⅲ,dihydropinosin and 3'-O-methylyam Ⅲ as an evaluation index,the extraction process was optimized by Box-Behnken response surface method.Subsequently,the extract's scavenging effects on DPPH,ABTS+free radicals,and inhibitory ability on tyrosinase were determined.RESULTS The optimal conditions were determined to be 49 min for ultrasound time,55％for ethanol concentration,1∶30 for solid-liquid ratio,and 2 times for extraction frequency,the total extraction content was 13.18 mg/g.The extract demonstrated the IC50 of 10.12,314.07 and 1.70 μg/g on DPPH,ABTS+free radicals and tyrosinase,respectively.CONCLUSION This simple,reliable and stable method can be used for the extraction for Bletillae Rhizoma with strong anti-oxidant,tyrosinase inhibitory activities.