OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside （acid） analogues that have been approved and marketed in China， such as entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide fumarate， and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs （2021 edition， trial implementation）， a comprehensive search was conducted across databases including CNKI， Wanfang Data， VIP， PubMed， the Cochrane Library， Embase， as well as relevant official websites. Drug package inserts， guidelines， consensus statements， and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions： safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility. RESULTS The scores for entecavir in terms of safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility-along with its comprehensive score-were 13， 14， 13， 10， 18， and 6， totaling 74 points. For tenofovir disoproxil fumarate， the respective scores were 13， 17， 18， 8， 18， and 7， totaling 81 points. For tenofovir alafenamide fumarate， the scores were 14， 20， 12， 8， 18， and 5， totaling 77 points. Finally， for tenofovir amibufenamide， the scores were 10.5， 17， 10， 6， 15， and 4， totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate， with the highest score， is recommended as the first-line option， suitable for adults， children， and pregnant women. However， caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative， particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside （acid） analogues should be individualized based on the patient’s age， physiological status， and risk factors.

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

Natural products (NPs) have long held a significant position in various fields such as medicine, food, agriculture, and materials. The chemical space covered by NPs is extensive but often underexplored. Therefore, high-throughput and efficient methodologies for the annotation and discovery of NPs are desired to address the complexity and diversity of NP-based systems. Mass spectrometry (MS) has emerged as a powerful platform for the annotation and discovery of NPs. MS databases provide vital support for the structural characterization of NPs by integrating extensive mass spectral data and sample information. Additionally, the released annotation methodologies, based on a variety of informatics tools, continuously improve the ability to annotate the structure and properties of compounds. This review examines the current mainstream databases and annotation methodologies, focusing on their advantages and limitations. Prospects for future technological advancements are then discussed in terms of novel applications and research objectives. Through a systematic overview, this review aims to provide valuable insights and a reference for MS-based NPs annotation, thereby promoting the discovery of novel natural entities.
Biological Products/chemistry* ; Mass Spectrometry/methods* ; Databases, Factual ; Drug Discovery/methods* ; Humans

(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.
Humans ; Ferroptosis/drug effects* ; Lymphoma, Non-Hodgkin/physiopathology* ; Cell Line, Tumor ; MAP Kinase Signaling System/drug effects* ; Animals ; Cell Proliferation/drug effects* ; Mice ; Apoptosis/drug effects* ; Membrane Proteins/genetics* ; Xenograft Model Antitumor Assays ; Male ; Mice, Nude

Objective:To explore the application value of radiomics models based on MRI of vertebrae and paravertebral muscles in identifying potential vertebral fragility fracture risk in osteoporosis and osteopenia.Methods:This cross-sectional study collected data from patients who underwent both dual-energy X-ray absorptiometry (DXA) and lumbar MRI at the Third Affiliated Hospital of Southern Medical University between January 2014 and December 2023,retrospectively. Based on DXA results, patients were categorized into osteoporosis group ( n=302) and osteopenia group ( n=264), with fracture and non-fracture patients matched at 1∶1 ratio by propensity score matching based on age, gender, and body mass index. The fourth lumbar vertebra was selected as the region of interest (ROI) for the vertebral body, and the bilateral psoas major, erector spinae, and multifidus muscles were selected as the ROIs for the paraspinal muscles. A total of 7 259 radiomics features were extracted from these ROIs. The dataset was divided into a training set and a test set in an 8∶2 ratio by simple random sampling (osteoporosis group 241 and 61 cases, osteopenia group 211 and 53 cases). The T-score was used to establish the clinical model. After feature normalization and dimensionality reduction, logistic regression was applied to build three radiomics models: vertebral model, paraspinal muscle model, and vertebral-paraspinal muscle model. The T-score was then combined with the radiomics model that achieved the highest area under the receiver operating characteristic curve (AUC) in the test set to construct a clinical-radiomics combined model. Model performance was evaluated using the AUC. The DeLong test was used to compare the diagnostic efficacy between models. Results:In the test set, the vertebral-paravertebral muscle model achieved the highest AUC among radiomics models and was selected for combination with the T-score. In identifying potential vertebral fragility fractures of osteoporosis group, the AUC (95% CI) of the clinical model, vertebral model, paraspinal muscle model, vertebral-paraspinal muscle model, and clinical-radiomics model were 0.523 (0.373-0.672), 0.869 (0.779-0.959), 0.608 (0.464-0.752), 0.876 (0.791-0.961), and 0.860 (0.769-0.952), respectively. For osteopenia group, the corresponding AUC(95% CI) were 0.625 (0.467-0.783), 0.696 (0.547-0.845), 0.706 (0.563-0.848), 0.816 (0.702-0.930), and 0.820 (0.710-0.930). The DeLong test showed that the vertebral model for identifying the potential vertebral fracture risk in osteoporosis group had better performance than the paraspinal muscle model ( Z=3.28, P=0.001). While for osteopenia group, there was no significant difference in diagnostic performance between the vertebral model and the paraspinal muscle model ( Z=0.09, P=0.932). The recognition efficacy of the clinical model and the vertebral-paraspinal muscle model was significantly different ( Z=3.69, 1.98; P<0.001, P=0.047), while there was no significant difference between the clinical-radiomics combined model and the vertebral-paraspinal muscle model ( Z=1.51, 0.12; P=0.131, 0.904). Conclusion:The MRI-based vertebral-paraspinal muscle radiomics model can effectively identify osteoporosis or osteopenia patients with potential fragility fracture risk. In osteopenia group, the efficacy of the MRI radiomics models based on the vertebra and paraspinal muscles in identifying potential vertebral fragility fracture risk is comparable.

Objective To explore the application value of simple drawing line puncture combined with visual articular process arthroplasty in lateral foraminoscopy.Methods A retrospective analysis was performed on 89 patients with single-segment lumbar disc herniation treated with lateral foraminoscopy from May 2019 to December 2022,including traditional transforaminal endoscopic spine system(TESSYS)technology(conventional group,35 cases)and simple drawing line puncture combined with visual articular process arthroplasty(modified group,54 cases).The fluoroscopy times,puncture time,and operation time of the two groups were compared.The Visual Analogue Score(VAS),Oswestry Disability Index(ODI),and MacNab criteria were used to evaluate the surgical effect at 3 d after surgery and at the last follow-up.Results All the operations were successfully completed without conversion to open surgery.In the conventional group,there was 1 case of L4 nerve root injury,who was considered intraoperative nerve root compression injury.There was no abnormality in lower limb muscle strength after surgery,but hyperalgesia and numbness in the innervated cutaneous area accompanied by nocturnal cramps.The patient was given treatment with pregabalin,mecobalamin,vitamin B1 and B6 for 2 months,and returned to normal at 1 year of follow-up.The other cases had no complications such as dural injury,abdominal organ injury,or incision infection.Recurrence occurred in 1 case in the conventional group and 2 cases in the modified group,and all the 3 cases occurred within 3 months after operation.Among them,2 patients had severe symptoms and underwent endoscopic revision again,and the other patient improved after conservative treatment.Compared with the conventional group,the puncture times[(1.8±0.7)times vs.(7.5±1.1)times,t=27.543,P=0.000].fluoroscopy times[(5.7±1.8)times vs.(23.2±2.2)times,t=41.235,P=0.000]and operation time[(72.7±7.2)min vs.(92.7±7.7)min,t=12.317,P=0.000]in the modified group were significantly reduced or shortened,and there was no significant difference in postoperative hospital stay[(3.2±0.6)d vs.(3.3±0.6)d,t=0.062,P=0.951]between the two groups.The conventional group was followed up for(14.0±1.3)months and the modified group was followed up for(13.6±1.2)months.There were no significant differences in VAS scores[(1.5±0.6)points vs.(1.6±0.7)points,t=0.751,P=0.455].ODI[(10.8±3.4)％vs.(11.8±3.9)％,t=1.284,P=0.202].and excellent and good rate of MacNab criteria[100％(54/54)vs.100％(35/35),Z=-0.981,P=0.327]between the two groups at the last follow-up.Conclusions Simple drawing line puncture combined with visual articular process arthroplasty can significantly improve the accuracy of intervertebral foramen aspiration,with simple operation,reduced X-ray exposure for doctors and patients,shortened operation time,and improved surgical safety.It is worthy of promotion and application in percutaneous foraminoscopy.

[Objective]To explore the relationships between the specifications of pills and medication and syndrome treatment in Jingui Yaolue,summarize ZHANG Zhongjing's academic thoughts of flexibly using pills.[Methods]Through studying Jingui Yaolue,combining the annotations of past generations and modern researches,this study summarized the specifications of the pills involved in the whole book based on the"quantity",interpreted the meaning of the specifications,analyzed the selection basis of different pill specifications from the two dimensions of medication and syndrome treatment,and summarized the academic thoughts of pills and its modern clinical significance.[Results]ZHANG Zhongjing established a two-dimensional specification system of"size-amount"of pills.The size of the pill was standardized by the quantitative unit and the amount of medicine was determined according to the single dosage and the frequency of medication.He emphasized that the amount of medicine was led through medication,paid attention to the unification of"medicinal properties-medicine quantity"and the balance of efficacy and poison.Moreover,he advocated clarifying the amount according to the syndrome treatment,flexibly adjusted the specifications of pills in terms of medicinal methods,objects and time of taking,and built a dynamic balance system of"specifications-medicine efficacy".This academic thoughts of using pills was based on specifications and deeply guided modern clinical practice.[Conclusion]ZHANG Zhongjing's academic thoughts of using pills takes"amount"as the core realized the unification of individualized medication and maximum therapeutic effect through specification selection.Based on the specifications of pills,focusing on"amount-effect"research,and integrating modern research results,it was expected to provide more accurate guidance for the clinical application of pills and promote its modern application.

Objective:To investigate the efficacy and safety of dupilumab in the treatment of elderly patients (≥ 60 years old) with atopic dermatitis (AD), with particular attention paid to rare adverse reactions.Methods:A single-center retrospective analysis was conducted on data collected from 281 elderly AD patients who received the standard regimen of dupilumab at the Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2020 to May 2024. Clinical characteristics such as gender, disease duration, skin lesion manifestations, and itch severity were analyzed. Changes in skin lesions and itch severity, as well as related adverse events were recorded during the follow-up period of 0 - 16 weeks. The efficacy and safety of dupilumab in the treatment of elderly AD patients were evaluated.Results:Among the 281 elderly AD patients, 214 were males (76.16%) and 67 were females (23.84%), with the age being 71.13 ± 7.91 years and the age at onset being 59.92 ± 15.72 years. The disease duration ( M[ IQR]) was 5.00 (13.00) years. After standard-regimen dupilumab treatment, the improvement rates of clinical outcome indicators SCORing Atopic Dermatitis (SCORAD) and pruritus numerical rating scale (NRS) scores gradually increased. At week 16, the improvement rates of SCORAD and NRS scores ( M[ IQR]) reached the maxima of 72.37% (23.89%) and 75.00% (29.72%), respectively. The overall incidence of adverse events was relatively low, with only 16 patients (6.05%) reporting adverse events. Common adverse reactions such as conjunctivitis (2 cases, 0.71%) and facial erythema (1 case, 0.36%) were mild and well-tolerated. Phenotype switching occurred in 10 cases (3.56%) . Conclusion:Dupilumab was an effective and safe treatment for elderly AD, but phenotype switching may occur.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.