Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

Objective:To explore the factors influencing healthcare-seeking time in diabetic foot patients and to develop and validate a predictive model for healthcare-seeking time.Methods:A total of 299 diabetic foot patients hospitalized in the Department of Endocrinology and Metabolism at the First Affiliated Hospital of Zhengzhou University from March 2023 to January 2024 were recruited for model development and internal validation. Sixty additional patients from the Second Affiliated Hospital of Zhengzhou University from September 2023 to January 2024 were used for external validation. Kaplan-Meier survival curves were used to estimate healthcare-seeking times. Cox regression analysis identified influencing factors and constructed the model. Random Survival Forest (RSF) was employed for variable selection and model construction. Internal validation was conducted using 10-fold cross-validation, and model evaluation utilized the integrated Brier score, C-index, and prediction error curve. Results:Kaplan-Meier analysis revealed that education level, foot self-care ability, lower extremity vascular disease, and disease perception significantly influenced healthcare-seeking time ( P<0.05). Cox regression identified gender, income level, medical payment method, living situation, marital status, ulcer history, social support, disease perception, and healthcare behavior perception as significant influencing factors ( P<0.05). RSF variable selection indicated that social support, disease perception, e-health literacy, healthcare behavior perception, and age were the most valuable factors for model construction. In external validation, the Brier scores for the Cox regression and RSF models were 0.059 and 0.088, respectively, while the C-indices were 0.862 and 0.683. Prediction error curves showed that the Cox regression model had lower prediction errors and higher predictive performance. Conclusions:The Cox regression model demonstrated superior performance and can assist nurses in effectively identifying high-risk populations for delayed healthcare-seeking in diabetic foot patients. This allows for timely interventions to improve healthcare behavior and reduce delays.

Objective:To explore the factors influencing healthcare-seeking time in diabetic foot patients and to develop and validate a predictive model for healthcare-seeking time.Methods:A total of 299 diabetic foot patients hospitalized in the Department of Endocrinology and Metabolism at the First Affiliated Hospital of Zhengzhou University from March 2023 to January 2024 were recruited for model development and internal validation. Sixty additional patients from the Second Affiliated Hospital of Zhengzhou University from September 2023 to January 2024 were used for external validation. Kaplan-Meier survival curves were used to estimate healthcare-seeking times. Cox regression analysis identified influencing factors and constructed the model. Random Survival Forest (RSF) was employed for variable selection and model construction. Internal validation was conducted using 10-fold cross-validation, and model evaluation utilized the integrated Brier score, C-index, and prediction error curve. Results:Kaplan-Meier analysis revealed that education level, foot self-care ability, lower extremity vascular disease, and disease perception significantly influenced healthcare-seeking time ( P<0.05). Cox regression identified gender, income level, medical payment method, living situation, marital status, ulcer history, social support, disease perception, and healthcare behavior perception as significant influencing factors ( P<0.05). RSF variable selection indicated that social support, disease perception, e-health literacy, healthcare behavior perception, and age were the most valuable factors for model construction. In external validation, the Brier scores for the Cox regression and RSF models were 0.059 and 0.088, respectively, while the C-indices were 0.862 and 0.683. Prediction error curves showed that the Cox regression model had lower prediction errors and higher predictive performance. Conclusions:The Cox regression model demonstrated superior performance and can assist nurses in effectively identifying high-risk populations for delayed healthcare-seeking in diabetic foot patients. This allows for timely interventions to improve healthcare behavior and reduce delays.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

OBJECTIVE: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. METHODS: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. RESULTS: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. CONCLUSION Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Network Pharmacology ; Data Mining ; Gastroesophageal Reflux/drug therapy*

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

Objective: To assess the feasibility of nuclear score combined with cyclin D1 immunocytochemistry in classifying indeterminate thyroid nodules with fine-needle aspiration (FNA) cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 118 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and April 2022 at the Department of Pathology, Beijing Hospital, China. These cases were subjected to cytological evaluation and cyclin D1 immunocytochemistry. The optimal cut-off points of a simplified nuclear score and the percentage of cyclin D1-positive cells for the diagnosis of malignancy or low-risk neoplasm were determined using the receiver operating characteristic (ROC) curves and area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of nuclear score and cyclin D1 immunostaining were evaluated from the crosstabs based on cut-off points. The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining was estimated using ROC curve analysis. Results: Nuclear grooves, intra-nuclear inclusions and chromatin clearing were more commonly found in malignancy/low-risk neoplasms than benign lesions (P=0.001, P=0.012 and P=0.001 respectively). A cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm, and its PPV, NPV, sensitivity and specificity were 93.6%, 87.5%, 99.0% and 50.0% respectively. A positive cut-off point of 10% positive thyroid cells in cyclin D1 immunostaining demonstrated sensitivity of 88.5%, specificity of 100%, PPV of 100% and NPV of 53.8% for correctly detecting thyroid malignancy or low-risk neoplasm. The sensitivity and PPV of simplified nuclear score combined with cyclin D1 immunostaining were 93.3% and 100%, respectively. Both specificity and NPV were maintained at high levels (100% and 66.7%, respectively). The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining in detecting thyroid malignancy/low-risk neoplasm was increased to 94.1% compared to using either of them alone. Conclusions: Combing simplified nuclear score and cyclin D1 immunostaining on FNA cytology specimens can increase the diagnostic accuracy in classifying thyroid nodules of indeterminate cytological categories. Thus, this supplementary approach provides a simple, accurate, and convenient diagnostic method for cytopathologists so that may reduce unnecessary thyroidectomies.
Humans ; Thyroid Nodule/pathology* ; Biopsy, Fine-Needle ; Cyclin D1 ; Immunohistochemistry ; Thyroid Neoplasms/pathology* ; Retrospective Studies

Objective    To analyze the safety and efficacy of vacuum-assisted venous drainage (VAVD) in cardiac surgery under cardiopulmonary bypass (CPB). Methods    A total of 180 patients from 3 centers between November 17, 2017 and October 1, 2018 were enrolled and randomly assigned to a VAVD group and a gravity drainage (GD) group by 1∶1 ratio. During the open-heart surgery under CPB, the VAVD group completely relied on VAVD, and the GD group used conventional GD. The primary endpoint was arterial flow before CPB, 15 min after aortic cross-clamping and rewarming to 36 °C of nasopharyngeal temperature. The secondary endpoints included hematocrit, hemoglobin concentration, blood product transfusion, etc. The safety endpoint was free hemoglobin concentration, etc. Results    The full analysis set contained 175 patients, 87 in the VAVD group and 88 in the GD group. Patients in the VAVD group were aged 52.8±12.0 years, and males accounted for 55.2%; patients in the GD group were aged 51.4±12.1 years, and males accounted for 59.1%. The demographic characteristics between the two groups were not statistically different. Compared to the GD group, the VAVD group could provide comparable arterial flow in CPB [average of 3 time points, 2.37±0.22 L/(min·m2) vs. 2.41±0.25 L/(min·m2), P=0.271], while not elevating free hemoglobin concentration. Conclusion    VAVD can provide enough venous drainage, while not elevating free hemoglobin concentration or damaging blood.