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.

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

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 impact of the interval between neoadjuvant immunotherapy combined with chemotherapy(nICT) and surgery on pathological outcomes and prognosis in patients.Methods:This is a retrospective cohort study. A total of 115 patients with locally advanced esophageal squamous cell carcinoma who underwent nICT followed by sequential surgery at Department of Thoracic Surgery, Peking University People′s Hospital or Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2024 were included. Among them, 99 were male and 16 were female, with an age of ( M(IQR)) 65 (11) years (range:45 to 81 years). All patients received 2 to 6 cycles of paclitaxel plus platinum-based doublet chemotherapy combined with PD-1 immune checkpoint inhibitors. The resectability of tumors was assessed based on CT scans of the chest and abdomen, and surgical approaches included Sweet surgery, Mckeown surgery, and Ivor-Lewis surgery. Patients were divided into a short-interval group (4 to <6 weeks) and a long-interval group (6 to 12 weeks) based on the interval between neoadjuvant immunochemotherapy and surgery. General patient data, surgical details, pathological response, and prognosis were collected and analyzed. Data comparisons were performed using independent sample t-test, Mann-Whitney U test, χ 2 test, or Fisher′s exact test. Multivariate logistic regression analysis was used to identify independent factors influencing pathological complete response (pCR). Survival analysis was conducted using the Kaplan-Meier method and Log-rank test. Results:There were no significant differences in baseline characteristics, neoadjuvant treatment details, surgical outcomes, or postoperative complications between the long-interval group and the short-interval group (all P>0.05). Multivariate Logistic regression analysis revealed that, among clinical factors, interval between neoadjuvant immunochemotherapy and surgery was significantly associated with pCR (long-interval group vs. short-interval group: OR=4.14, 95% CI:1.63 to 10.50, P=0.003). The pCR rate was higher in the long-interval group (43.6% vs. 17.1%, χ2=6.48, P=0.011). Survival analysis showed no significant differences in overall survival ( P=0.094) or disease-free survival ( P=0.840) between the two groups. Conclusion:Appropriately extending the surgical interval after neoadjuvant immunochemotherapy maybe lead to a higher pCR rate, without increasing surgical difficulty or damaging prognosis.

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 analyze and compare the efficacy of DNA barcode,i.e.,Cytochrome b(Cytb)and 12S ribosomal RNA(12S rRNA)gene sequences,in the species identification of wildlife.Methods DNA extraction,quantification,PCR amplification of Cytb and 12S rRNA gene fragments,Sanger sequencing,and sequence alignment analysis were performed on ten wildlife samples.Results Both gene fragments were successfully amplified in six samples,while Cytb alone was successfully amplified in 1 sample,and 12S rRNA alone in 3 samples.Sequence analysis indicated that Cytb enabled species-level identification for 6 samples(Gallinula chloropus,Streptopelia orientalis,Phasianus colchicus,Falco naumanni,Myiopsitta monachus and Lynx lynx)and genus-level identification for 1 sample(Lepus).In contrast,12S rRNA achieved species-level identificaggion for 8 samples(Gallinula chloropus,Lepus sinensis,Phasianus colchicus,Myiopsitta monachus,Muntiacus reevesi,Macaca mulatta and Lynx lynx),representing seven species,and genus-level identification for 1 sample(Falco).However,by combining Cytb and 12S rRNA,all samples could be identified to the species level.Conclusion When applying DNA barcodes to wildlife identification,the Cytb and 12S rRNA gene regions analyzed here can effectively identify common species such as Gallinula chloropus and Streptopelia orientalis,but face difficulties in distinguishing closely related species within the same genus.Therefore,when conducting wildlife species identification,it is recommended to use two or more DNA barcode markers.