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.

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 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 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 evaluate the diagnostic value of coronary angiography-derived fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) for identifying coronary functional abnormalities.Methods:This diagnostic study enrolled patients with clinically suspected or diagnosed coronary artery disease who underwent coronary angiography at Beijing Anzhen Hospital, TEDA International Cardiovascular Hospital, and Qilu Hospital of Shandong University between December 2021 and June 2022. All enrolled patients successfully underwent invasive wire-based FFR and IMR measurements during angiography. In a core laboratory, FFR and IMR for the target vessels were measured using artificial intelligence technology based on coronary angiographic images. Spearman correlation analysis was used to evaluate the correlation between angiography-derived FFR and wire-based FFR, and between angiography-derived IMR and wire-based IMR. Coronary hemodynamic abnormality was defined as FFR≤0.80; the diagnostic performance of angiography-derived FFR for identifying this abnormality was evaluated. Microcirculatory dysfunction was defined as IMR≥25; the diagnostic performance of angiography-derived IMR for identifying microcirculatory dysfunction was evaluated.Results:A total of 181 patients, aged (60.6±8.8) years, with 62 (34.3%) females, and 181 target vessels were included in the final analysis. Angiography-derived FFR showed a significant positive correlation with wire-based FFR ( r=0.78, P<0.001). For identifying coronary hemodynamic abnormality, angiography-derived FFR showed an accuracy of 89.0%, sensitivity of 88.8%, specificity of 89.1%, positive predictive value (PPV) of 88.8%, negative predictive value (NPV) of 89.1%, and an area under the receiver operating characteristic curve ( AUC) of 0.88. Angiography-derived IMR showed a significant positive correlation with wire-based IMR ( r=0.93, P<0.001). For identifying microcirculatory dysfunction, angiography-derived IMR demonstrated an accuracy of 89.5%, sensitivity of 86.8%, specificity of 90.2%, PPV of 70.2%, NPV of 96.3%, and an AUC of 0.95. Conclusion:Angiography-derived FFR and IMR exhibit strong correlations with their invasive wire-based counterparts and demonstrate high diagnostic value for assessing coronary hemodynamics and coronary microcirculatory function.

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.

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.