Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Objective To investigate the correlation between serum Irisin,long pentraxin 3(PTX3),human metas-tasis-associated lung adenocarcinoma transcript 1(MALAT1)levels and the severity of diabetic retinopathy(DR)and the value of combined diagnosis.Methods Eighty-five patients with type 2 diabetes mellitus(T2DM)combined with DR at Cangzhou Central Hospital from April 2022 to April 2023 were selected as the DR group,85 patients with T2DM alone were selected as the non-DR group,and 85 healthy volunteers were selected as the control group during the same period.Pa-tients in the DR group were further divided into the proliferative DR(PDR)group(38 patients)and the non-PDR group(47 patients)based on whether DR was in the proliferative phase.Clinical data of patients in the DR group were collected,including gender,diastolic pressure,age,systolic pressure,disease course,fasting plasma glucose(FPG),body mass in-dex,hemoglobin A1c(HbA1c),smoking history,triglyceride(TG),drinking history,peak systolic velocity(PSV),peak end-diastolic velocity(PEDV),resistance index(RI),fasting insulin(FINS),family history of diabetes,total cholesterol(TC),and homa-insulin resistance(HOMA-IR).Enzyme-linked immunosorbent assay was used to detect serum levels of Irisin and PTX3 in each group of patients,and real-time quantitative polymerase chain reaction was used to detect the ser-um level of MALAT1.The correlations between serum levels of Irisin,PTX3 and MALAT1 and the severity of DR were ana-lyzed using the Pearson correlation coefficient.The influencing factors of the DR severity were identified using the Logistic regression.The value of serum Irisin,PTX3,and MALAT1 levels in diagnosing DR alone was analyzed using the receiver operating characteristic(ROC)curve.The value of regimens containing and not containing serum Irisin,PTX3,and MAL-AT1 levels in diagnosing DR was analyzed using the ROC curve,net reclassification index(NRI),and integrated discrimina-tion improvement(IDI)index.Results The serum levels of Irisin,PTX3,and MALAT1 were compared among the three groups of patients,and the differences were statistically significant(all P＜0.001).The disease course of patients in the PDR group was longer than that in the non-PDR group,the PSV,PEDV and serum Irisin level were lower than those in the non-PDR group,while the RI,FPG,HbA1c,TG,FINS,HOMA-IR,and serum PTX3 and MALAT1 levels were higher than those in the non-PDR group(all P＜0.05).The serum Irisin level in DR patients was negatively correlated with the severity of DR(r=-0.512,P＜0.001),while the PTX3 and MALAT1 levels were positively correlated with the severity of DR(r=0.497,0.573,both P＜0.05).The Logistic regression analysis showed that the disease course,FPG,HbA1c,TG,FINS,HOMA-IR,PSV,PEDV,RI,and serum levels of Irisin,PTX3 and MALAT1 were influencing factors for the DR progression(allP＜0.05).The area under the curve(AUC)of serum Irisin,PTX3,and MALAT1 levels in diagnosing DR was 0.743,0.811,and 0.773,respectively.Compared with conventional diagnostic protocols,the AUC of the new diagnostic protocol containing serum levels of Irisin,PTX3,and MALAT1 significantly increased(Z=2.708,P=0.007),and the NRI and IDI were 0.039(95％CI:0.022-0.069)and 0.026(95％CI:0.014-0.047),respectively(all P＜0.05).Conclusion The serum Irisin level in DR patients decreases,while the serum PTX3 and MALAT1 levels increase,which are closely related to the severity of DR.Diagnostic plans containing serum Irisin,PTX3,and MALAT1 indicators have high diagnostic value.

Objective:To investigate the practicality of TrueFidelity deep learning reconstruction algorithm in low-dose abdominal and pelvic CT angiography (CTA).Methods:The patients who required abdominal and pelvic CTA were prospectively included at the First Affiliated Hospital of Xi′an Jiaotong University from June 2020 to March 2021. All patients underwent low-dose CTA with a tube voltage of 80 kV and smart tube current modulation (100-720 mA). Images were reconstructed using the traditional FBP, adaptive statistical iterative reconstruction with a strength of 50% (ASIR-V 50%), TrueFidelity with medium (TF-M) and high (TF-H) strength. The CT value and standard deviation (SD value) of the abdominal aorta, psoas major muscle and subcutaneous fat in the same layer were measured, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated. We also introduced the measurement of skewness of CT value in psoas major muscle with uniform density. The above indexes of the four groups of reconstructed images were compared. A 5-point scoring method was used to evaluate the granularity, fuzziness and beam-hardening artifacts of all images. Objective measurement indicators, such as CT values, were tested by repeated measure ANOVA with the Bonferroni post hoc test.Results:There were forty-six patients in the study. The volume CT dose index of the scan was low at (1.09±0.31)mGy. There was no significant difference in CT values of vessels and muscles between the four groups ( P>0.05), but there was a significant difference in SD value( P<0.001). The SD value of the FBP group was the largest and that of the TF-H group was the smallest. The difference between SNR and CNR was statistically significant ( P<0.001), and the overall trend was opposite to that of the SD value. There was no significant difference in the skewness between the four groups. The granularity score of the FBP group was the largest, that of the TF-H group was the smallest, and there was a significant difference among the four groups. The score of fuzziness in the TF-H group was slightly higher than that in the other three groups, but there was no significant difference. The beam-hardening artifact score of FBP and ASIR-V 50% group was the worst, and the TF-H group was the best ( P<0.001). Conclusions:Compared with FBP and ASIR-V, TrueFidelity reconstruction algorithm provides better image quality (comprehensively considering image noise, fuzziness, uniformity, and hardening artifacts) in low-dose CT scanning of abdominal and pelvic vessels, and TF-H has the best image quality.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

Objective:To explore the causal association of glucose-lipid metabolism and obesity indicators with myocardial infarction by a two-sample Mendelian randomization analysis.Methods:Single nucleotide polymorphisms (SNPs) related to phenotypes were obtained from genome-wide association study databases. The body mass index (BMI) and glycated hemoglobin dataset includes 99 998 samples and 8 126 035 SNPs; the waist-to-hip ratio dataset includes 224 459 samples and 2 562 516 SNPs; the waist circumference and hip circumference dataset includes 462 166 samples and 9 851 867 SNPs; the fasting glucose dataset includes approximately 12 million SNPs; the low-density lipoprotein cholesterol (LDL-C) dataset includes 201 678 samples and 12 321 875 SNPs; the high-density lipoprotein cholesterol (HDL-C), and triglycerides dataset includes 156 109 samples and 15 784 414 SNPs; and the body fat percentage, whole-body fat mass, trunk fat percentage, and trunk fat mass dataset includes 454 588 samples and 9 851 867 SNPs. This study primarily used inverse-variance weighted method to analyze the associations between various exposure factors and outcomes. Heterogeneity among SNPs was assessed using Cochran′s Q test, and horizontal pleiotropy of SNPs was examined using the MR-Egger method. Additionally, a multivariable MR approach was used to adjust for BMI, further validating associations between exposure factors and the risk of myocardial infarction. Results:Higher BMI ( OR=1.070, 95% CI: 1.041-1.100), waist-to-hip ratio ( OR=1.366, 95% CI: 1.113-1.677), LDL-C ( OR=1.638, 95% CI: 1.488-1.803), triglycerides ( OR=1.445, 95% CI: 1.300-1.606), waist circumference ( OR=1.841, 95% CI: 1.650-2.055), hip circumference ( OR=1.247, 95% CI: 1.132-1.372), body fat percentage ( OR=1.795, 95% CI: 1.568-2.055), whole-body fat mass ( OR=1.519, 95% CI: 1.381-1.670), trunk fat percentage ( OR=1.538, 95% CI: 1.374-1.723), and trunk fat mass ( OR=1.421, 95% CI: 1.294-1.561), as well as lower HDL-C ( OR=0.799, 95% CI: 0.729-0.875), have causal effects on myocardial infarction (all P<0.05). After adjusting for BMI, hip circumference, trunk fat percentage, and trunk fat mass were no longer associated with myocardial infarction. However, waist-to-hip ratio ( OR=1.457, 95% CI: 1.132-1.877), fasting glucose ( OR=1.191, 95% CI: 1.024-1.383), glycated hemoglobin ( OR=1.129, 95% CI: 1.034-1.233), LDL-C ( OR=1.592, 95% CI: 1.314-1.929), triglycerides ( OR=1.410, 95% CI: 1.279-1.553), waist circumference ( OR=1.922, 95% CI: 1.448-2.551), body fat percentage ( OR=1.421, 95% CI: 1.072-1.884), and whole-body fat mass ( OR=1.295, 95% CI: 1.031-1.626) remained positively associated with myocardial infarction, while HDL-C ( OR=0.809, 95% CI: 0.729-0.897) remained negatively associated. Conclusions:Abdominal obesity and dysregulation of glucose-lipid metabolism are risk factors for myocardial infarction. Screening for glucose-lipid metabolism (fasting glucose, HDL-C, LDL-C, triglycerides) and obesity-related indicators (waist circumference, waist-to-hip ratio, body fat percentage, and whole-body fat mass) is of great importance for the primary prevention of myocardial infarction.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.