Background: The global rise in visual impairment, driven by population aging, the increasing prevalence of lifestyle-related chronic diseases, and environmental factors, has made it a critical public health concern, highlighting the urgent need for effective preventive strategies and eye health maintenance. Cuscutae Semen (CS), a traditional Chinese herbal medicine long regarded for its vision-enhancing properties, has been widely used to support ocular health. However, its underlying molecular mechanisms and bioactive constituents remain poorly understood, limiting its modernization and broader clinical application. Objective: This study aims to investigate the restorative effects of CS on visual impairment, elucidate its underlying mechanisms, and identify potential active components. Methods: A zebrafish model of visual impairment was established using mepanipyrim to simulate retinal structural damage and visual dysfunction. The therapeutic effects of CS were systematically evaluated through behavioral analyses and histomorphological observations. To elucidate the underlying mechanisms, an integrated approach was employed, combining transcriptome sequencing (RNA-seq), reverse transcription quantitative polymerase chain reaction validation, and immunofluorescence staining to identify critical genes and pathways involved. Furthermore, macroporous resin column chromatography was employed for the fractionation and screening of potential active components. Results: CS treatment significantly alleviated mepanipyrim-induced ocular abnormalities in zebrafish, restoring approximately 82% of the observed morphological defects. Behavioral assessments revealed that CS-treated zebrafish exhibited markedly increased swimming speed and distance, indicating enhanced visual light sensitivity. Histopathological analysis demonstrated that CS effectively repaired the structure of retinal cell layers. RNA-seq revealed that CS broadly reversed mepanipyrim-induced gene expression disturbances, suggesting a restorative effect on transcriptomic homeostasis. Gene Ontology enrichment analysis identified the phototransduction pathway as a key mediator of CS’s therapeutic effects. This was further supported by reverse transcription quantitative polymerase chain reaction validation of critical genes and immunofluorescence staining, which confirmed the restored expression of Pde6a and Gnat2, key proteins involved in photic signal transmission. Active component screening indicated that high-polar constituents, including chlorogenic acid, may constitute one of the major bioactive fractions responsible for the observed therapeutic effects. Conclusion: This study provides evidence of the vision-protective effects of CS in a zebrafish model, demonstrating that its therapeutic mechanism involves modulation of the phototransduction pathway. Chlorogenic acid was identified as one of the key bioactive constituents contributing to this effect. These findings not only provide scientific validation for the traditional use of CS in ocular protection but also present promising therapeutic prospects for the prevention and treatment of visual impairment.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/chemistry* ; Taste

Objective To investigate the risk factors for pneumonia complicating infectious mononucleosis(IM)in adults and construct a nomogram prediction model.Methods A retrospective analysis was conducted on 198 IM patients admitted to the Second Affiliated Hospital of Air Force Medical University from January 2015 to December 2021.Patients were divided into pneumonia group(n=52)and non-pneumonia group(n=146)based on whether pulmonary infection occurred during hospitalization.The baseline data(age,gender,place of onset,etc.),clinical manifestations(maximum body temperature,lymph node enlargement,splenomegaly,etc.),and inflammatory indicators[white blood cell count(WBC),C-reactive protein(CRP),etc.]were compared between the two groups.Kaplan-Meier curves were plotted to analyze the key indicators affecting the hospital stay of IM patients.Multivariate logistic regression was used to analyze the independent risk factors for pneumonia complicating IM in adults and construct a nomogram prediction model based on the identified risk factors.The predictive efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve and the consistency of the model was assessed using the calibration curve.The fit of the model was evaluated using the Hosmer-Lemeshow test.Additionally,the sensitivity,specificity,and accuracy of the model were assessed using confusion matrix.Results Compared with non-pneumonia group,the pneumonia group had a significantly higher proportion of patients from rural areas,with body mass index(BMI)≥24 kg/m2,smoking history,hepatomegaly,fever duration of≥7 d,as well as increased total hospitalization costs and average daily hospitalization costs,and prolonged hospital stay(P<0.05).The proportion of patients with a history of antibiotic use was lower in the pneumonia group(P<0.05).Kaplan-Meier survival analysis showed that patients from rural areas,with BMI≥24 kg/m2,smoking history,no prophylactic use of antibiotics,fever duration≥7 d,and hepatomegaly had significantly prolonged hospital stays(P<0.05).Multivariate logistic regression analysis revealed that living in a rural area(OR=4.089,P<0.05),hepatomegaly(OR=4.082,P<0.05),and elevated WBC(OR=1.205,P<0.05)were independent risk factors for pneumonia complicating IM in adults,while the prophylactic use of antibiotics(OR=0.142,P<0.05)was an independent protective factor.The area under the ROC curve of the constructed nomogram prediction model was 0.827(95%CI 0.762-0.892),and the slope of the calibration curve was close to 1,and the Hosmer-Lemeshow test showed χ2=5.299,P=0.725,indicating good consistency and fit of the prediction model.The results of the confusion matrix assessment showed that the sensitivity of the model was 0.669(0.624-0.773),the specificity was 0.827(0.724-0.930),and the accuracy was 0.732(0.665-0.793).Conclusion The nomogram prediction model based on place of onset,hepatomegaly,the prophylactic use of antibiotics and WBC has excellent fit and discrimination,providing an effective quantitative tool for prognosis assessment of IM.

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Objective:To investigate the effect of chrysophanol(CHR)on cartilage injury in rats with osteoarthritis and its mechanism of regulating SIRT1/HMGB1/NF-κB signal pathway.Methods:Rat models of osteoarthritis were established and divided into negative control group,chrysophanol low(CHR-L,10 mg/kg),middle(CHR-M,20 mg/kg),high dose group(CHR-H,40 mg/kg),SIRT1 inhibitor(sirtinol 5 mg/kg)+chrysophanol high dose group(sirtinol+CHR-H),and normal healthy control group was set up.The degree of joint swelling was measured,and the inflammatory index was evaluated;the pain threshold(tenderness and heat pain)was measured;HE staining and safranine O staining were applied to detect the pathological changes of rat articular cartilage;the levels of serum inflammatory factors(IL-6,IL-1β,TNF-α)were detected by ELISA method;oxidative stress indexes(MDA,SOD,GSH-PX)were detected by micro method;TUNEL staining was used to detect apoptosis;Western blot was used to detect the protein expressions of SIRT1,HMGB1,NF-κB p65,p-NF-κB p65,MMP-13 and C-Caspase-3.Results:Compared with the normal healthy control group,the rats in negative control group had obvious pathological injury,such as destruction of articular cartilage structure,necrosis and reduction of chondrocytes,the joint swelling degree,arthritis index,levels of IL-6,IL-1β,TNF-α,content of MDA,chondrocyte apoptosis rate,expressions of apoptotic protein C-Caspase-3,HMGB1,NF-κB p65/p-NF-κB p65,MMP-13 proteins increased obviously,the tenderness threshold,heat pain threshold,activities of SOD,GSH-PX,and the expression of SIRT1 protein decreased obviously(P<0.05);compared with negative control group,the pathological injury of articular cartilage in CHR group improved obviously with the increase of dosage,the joint swelling degree,arthritis index,levels of IL-6,IL-1β,TNF-α,content of MDA,chondrocyte apoptosis rate,expression of apoptotic protein C-Caspase-3,HMGB1,NF-κB p65/p-NF-κB p65,MMP-13 proteins decreased obviously,the tenderness threshold,heat pain threshold,activities of SOD,GSH-PX,and the expression of SIRT1 protein increased obviously(P<0.05);compared with CHR-H group,sirtinol+CHR-H group was able to reverse the protective effect of CHR on cartilage injury to a certain extent.Conclusion:CHR can reduce the inflammation of articular cartilage,inhibit the apoptosis of chondrocytes and play a protective role in the cartilage injury of osteoarthritis rats by up-regulating the expression of SIRT1 and down-regulating the expressions of HMGB1 and NF-κB p65/p-NF-κB p65.

Objective·To investigate the predictive value of the geriatric nutritional risk index(GNRI)for the occurrence of lung infection in hospitalized elderly patients with type 2 diabetes mellitus(T2DM).Methods·Elderly T2DM patients who were admitted to the Geriatric Department of Shanghai Tongren Hospital between June 2022 and June 2024 were retrospectively and consecutively enrolled.They were divided into infected and non-infected groups according to whether lung infection occurred during hospitalization.Baseline data(gender,age,height,weight,duration of diabetes,comorbidities,etc.)were collected and GNRI was calculated.A multivariate Logistic regression model was used to screen the independent risk factors for pulmonary infections,and the predictive value of GNRI for pulmonary infections in T2DM patients was analysed using receiver operating characteristic(ROC)curves.Results·A total of 264 elderly T2DM patients were enrolled,among whom 154 developed pulmonary infections.Significant differences were observed between the infected and non-infected groups in GNRI,albumin,leukocyte count,neutrophil ratio,lymphocyte ratio,glycated hemoglobin,fasting glucose,interleukin-6,C-reactive protein,and procalcitonin levels(P<0.05).Multivariate Logistic regression analysis showed that a lower GNRI was an independent risk factor for lung infection(OR=0.798,95%CI 0.712?0.894;P<0.001).Correlation analysis showed that GNRI was negatively correlated with C-reactive protein and calcitoninogen.ROC curve analysis showed that GNRI predicted pulmonary infection with an area under the curve of 0.828,a sensitivity of 77.9%,and a specificity of 76.6%.Conclusion·A lower GNRI is an independent risk factor for pulmonary infections in elderly T2DM patients,and also has a good predictive value for the occurrence of pulmonary infections.

Objective·To investigate the predictive value of the geriatric nutritional risk index(GNRI)for the occurrence of lung infection in hospitalized elderly patients with type 2 diabetes mellitus(T2DM).Methods·Elderly T2DM patients who were admitted to the Geriatric Department of Shanghai Tongren Hospital between June 2022 and June 2024 were retrospectively and consecutively enrolled.They were divided into infected and non-infected groups according to whether lung infection occurred during hospitalization.Baseline data(gender,age,height,weight,duration of diabetes,comorbidities,etc.)were collected and GNRI was calculated.A multivariate Logistic regression model was used to screen the independent risk factors for pulmonary infections,and the predictive value of GNRI for pulmonary infections in T2DM patients was analysed using receiver operating characteristic(ROC)curves.Results·A total of 264 elderly T2DM patients were enrolled,among whom 154 developed pulmonary infections.Significant differences were observed between the infected and non-infected groups in GNRI,albumin,leukocyte count,neutrophil ratio,lymphocyte ratio,glycated hemoglobin,fasting glucose,interleukin-6,C-reactive protein,and procalcitonin levels(P<0.05).Multivariate Logistic regression analysis showed that a lower GNRI was an independent risk factor for lung infection(OR=0.798,95%CI 0.712?0.894;P<0.001).Correlation analysis showed that GNRI was negatively correlated with C-reactive protein and calcitoninogen.ROC curve analysis showed that GNRI predicted pulmonary infection with an area under the curve of 0.828,a sensitivity of 77.9%,and a specificity of 76.6%.Conclusion·A lower GNRI is an independent risk factor for pulmonary infections in elderly T2DM patients,and also has a good predictive value for the occurrence of pulmonary infections.

Objective:To investigate the effect of chrysophanol(CHR)on cartilage injury in rats with osteoarthritis and its mechanism of regulating SIRT1/HMGB1/NF-κB signal pathway.Methods:Rat models of osteoarthritis were established and divided into negative control group,chrysophanol low(CHR-L,10 mg/kg),middle(CHR-M,20 mg/kg),high dose group(CHR-H,40 mg/kg),SIRT1 inhibitor(sirtinol 5 mg/kg)+chrysophanol high dose group(sirtinol+CHR-H),and normal healthy control group was set up.The degree of joint swelling was measured,and the inflammatory index was evaluated;the pain threshold(tenderness and heat pain)was measured;HE staining and safranine O staining were applied to detect the pathological changes of rat articular cartilage;the levels of serum inflammatory factors(IL-6,IL-1β,TNF-α)were detected by ELISA method;oxidative stress indexes(MDA,SOD,GSH-PX)were detected by micro method;TUNEL staining was used to detect apoptosis;Western blot was used to detect the protein expressions of SIRT1,HMGB1,NF-κB p65,p-NF-κB p65,MMP-13 and C-Caspase-3.Results:Compared with the normal healthy control group,the rats in negative control group had obvious pathological injury,such as destruction of articular cartilage structure,necrosis and reduction of chondrocytes,the joint swelling degree,arthritis index,levels of IL-6,IL-1β,TNF-α,content of MDA,chondrocyte apoptosis rate,expressions of apoptotic protein C-Caspase-3,HMGB1,NF-κB p65/p-NF-κB p65,MMP-13 proteins increased obviously,the tenderness threshold,heat pain threshold,activities of SOD,GSH-PX,and the expression of SIRT1 protein decreased obviously(P<0.05);compared with negative control group,the pathological injury of articular cartilage in CHR group improved obviously with the increase of dosage,the joint swelling degree,arthritis index,levels of IL-6,IL-1β,TNF-α,content of MDA,chondrocyte apoptosis rate,expression of apoptotic protein C-Caspase-3,HMGB1,NF-κB p65/p-NF-κB p65,MMP-13 proteins decreased obviously,the tenderness threshold,heat pain threshold,activities of SOD,GSH-PX,and the expression of SIRT1 protein increased obviously(P<0.05);compared with CHR-H group,sirtinol+CHR-H group was able to reverse the protective effect of CHR on cartilage injury to a certain extent.Conclusion:CHR can reduce the inflammation of articular cartilage,inhibit the apoptosis of chondrocytes and play a protective role in the cartilage injury of osteoarthritis rats by up-regulating the expression of SIRT1 and down-regulating the expressions of HMGB1 and NF-κB p65/p-NF-κB p65.