OBJECTIVE To comprehensively analyze the effectiveness， safety and economic value of carfilzomib in the treatment of multiple myeloma （MM）， and provide evidence-based guidance for clinical rational drug use. METHODS A systematic search was performed in PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang， VIP， and relevant health technology assessment （HTA） websites， from database inception to December 31， 2024. Two researchers independently screened studies based on predefined inclusion and exclusion criteria， extracted data， and assessed study quality. Descriptive statistical analyses were conducted. RESULTS A total of 21 studies were included， comprising 7 systematic reviews/meta-analyses， 5 clinical trials， 5 pharmacoeconomic studies， and 4 HTA reports. Effectiveness analysis indicated that， compared with control groups， carfilzomib significantly improved overall response rate and clinical benefit rate （ P ＜0.05）， prolonged progression-free survival， and enhanced patient’s quality of life （ P ＜0.05）， while its impact on overall survival remains to be further confirmed. Safety analysis showed there was no significant difference in the risk of peripheral neuropathy between carfilzomib and controls， while the risks of cardiotoxicity and hypertension were significantly increased （ P ＜0.05）. Economic analysis suggested that carfilzomib regimens demonstrated certain cost-effectiveness in second-line treatment in the U.S. and some European countries. However， its economic value was influenced by drug price， dosing regimen， and regional differences， and it may lack a cost advantage in some countries or in third-line treatment. CONCLUSIONS Carfilzomib shows definite efficacy and generally acceptable safety in the treatment of MM， but cardiotoxicity and hypertension risks require careful monitoring. Given its high treatment cost， pharmacoeconomic studies in the Chinese population are urgently needed.

Objective: To investigate the incidence of occult hepatitis B virus infection (OBI) in spouses of asymptomatic hepatitis B virus (HBV) infected individuals in Shenzhen, China, and to analyze their serological and molecular characteristics and possible transmission routes, so as to propose refined strategies for blood safety. Methods: After rapid screening for HBsAg at the blood collection sites, samples from HBsAg-positive blood donors and their concurrently donating spouses were collected. All samples were tested for hepatitis B serological markers by electrochemiluminescence immunoassay (ECLI). Simultaneously, HBV nucleic acid extractiona, nested PCR amplification, gene sequencing of S and BCP/PC regions and qPCR were conducted. Results: A total of 112 samples were collected, including 56 from HBsAg positive donors and 56 from their spouses. All donors were confirmed as HBsAg+/DNA+/anti-HBc+, indicative of asymptomatic chronic hepatitis (CHB) infection. Among their 56 spouses, 11 (19.6%) were identified as HBV DNA+. The prevalence was higher in males (23.1%) than in females (16.7%). Six spouses (10.8%) had OBI, three of whom (5.4%) were negative in routine blood screening tests. The residual risk of HBV were estimated as 1∶127 (95%CI, 1∶356 to 1∶66). Among infected couples, immune escape mutation (E164D) and glycosylation mutations (I126T and T131N/M133T) were identified. Furthermore, sequence analysis suggested partner-to-partner transmission in eight cases. Conclusion: A substantial proportion (19.6%) of spouses of asymptomatic HBV infected donors were HBV-positve, with an OBI prevalence of 10.9%. Among these, 5.4% were negative in routine tests. To ensure blood safety, we recommend that spouses of HBV infected individuals be deferred from blood donation.

Aerosol removal using flame-retardant atomized fixatives, as a major means of aerosol control, has achieved remarkable results in the field of nuclear facility decommissioning and decontamination. Traditional atomized fixatives for aerosol removal have deficiencies in high-temperature resistance and flame retardancy, rendering them inadequate for operational scenarios involving high temperatures and flammability encountered during nuclear decommissioning. This paper investigates the current development of flame-retardant atomized fixatives for aerosol removal both domestically and internationally and presents a preliminary exploration of this technology. The experiments showed that atomized fixatives modified with flame-retardant properties not only maintained excellent aerosol capture efficiency, but also exhibited significantly improved flame-retardant performance. This confirmed the technical feasibility of the proposed approach. Finally, suggestions and reflections are proposed for the development of this technology and its application in nuclear facility decommissioning.

OBJECTIVE To predict and validate the mechanisms of Chaiqi yigan granules （CQYG） improving hepatocellular carcinoma （HCC）. METHODS The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group （normal saline）， sorafenib group （positive control， 50 mg/kg）， and CQYG low-， medium- and high-dose groups （24.83， 49.66， 99.32 g/kg）， with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， for 14 consecutive days. After last administration， pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition （EMT） [N-cadherin， E-cadherin， Vimentin， matrix metalloproteinase 7 （MMP7）] and the mitogen-activated protein kinase （MAPK） signaling pathway [p38 MAPK， phosphorylated p38 MAPK， c-Jun N-terminal kinase （JNK）， phosphorylated JNK， extracellular regulated protein kinase 1/2 （ERK1/2）， phosphorylated ERK1/2] in tumor tissue of mice. RESULTS Network pharmacology analysis revealed that metabolic pathways， pathways in cancer， and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments， the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group， CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover， the expression levels of Ki-67， N-cadherin， MMP7 and Vimentin proteins， along with the phosphorylation levels of ERK1/2 and JNK proteins， were all significantly reduced （ P ＜0.05）. The expression level of E-cadherin protein was significantly increased （ P ＜0.05）， the phosphorylation level of p38 MAPK protein was increased， the difference was not statistically significant （ P ＞0.05）. CONCLUSIONS CQYG can inhibit EMT by regulating the MAPK signaling pathway， thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.

OBJECTIVE To evaluate the cost-effectiveness of amivantamab combined with lazertinib （hereinafter referred to as “AL”） regimen as first-line treatment for EGFR -mutated advanced non-small cell lung cancer （NSCLC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was established based on updated data from the MARIPOSA study， with a 10-year time horizon and 28-day cycles. The primary outcome index was quality adjusted life year （QALY）， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024 （287 247 yuan/QALY）. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of AL regimen versus osimertinib monotherapy regimen as first-line treatment for EGFR -mutated advanced NSCLC. One-way and probabilistic sensitivity analyses were performed to test model robustness. Scena rio analyses were conducted to explore the impact of utility values for different health states on the outcomes and determine the required price reductions of amivantamab and lazertinib to achieve cost-effectiveness. RESULTS Compared with the osimertinib monotherapy regimen， the ICER for the AL regimen as first-line treatment for advanced EGFR -mutated NSCLC was 2 062 096.15 yuan/QALY， significantly exceeding the WTP threshold established in this study. One-way sensitivity analysis revealed that the utility value of progression-free survival state and the price of amivantamab were the primary factors influencing the ICER. Probabilistic sensitivity analysis revealed that the AL regimen only became cost-effective when the WTP threshold was set at 2 050 000 yuan/QALY. Scenario analysis indicated that altering the utility value still rendered the AL regimen non-cost-effective. When amivantamab （350 mg） prices decreased by 80%， 85%， and 90% respectively， lazertinib （80 mg） prices would need to decrease by 95.97%， 40.63%， 5.29%， respectively. This would enable the AL regimen’s ICER to consistently fall within the WTP threshold established in this study. CONCLUSIONS At the WTP threshold established in this study， the AL regimen does not demonstrate cost-effectiveness for first-line treatment of advanced EGFR -mutated NSCLC compared to the osimertinib monotherapy regimen. Significant price reductions for both drugs would be required to alleviate the financial burden on patients.

ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

Objective To understand the current status of low-density lipoprotein cholesterol (LDL-C) control in patients after coronary artery bypass grafting (CABG). Methods Clinical data of patients who underwent isolated CABG in Beijing Anzhen Hospital in 2023 were collected. All patients returned to our hospital approximately one year after surgery (10-13 months) for a lipid level recheck. We analyzed their LDL-C attainment status and influencing factors. Patients were categorized into two groups based on whether their LDL-C met the target: a LDL-C attainment group and a LDL-C non-attainment group. Results This study included 1456 patients who underwent CABG, including 320 females and 1136 males, with an average age of (61.41±9.12) years. One year post-surgery, 234 patients achieved the LDL-C target, with an attainment rate of 16.07%. The proportion of patients in the LDL-C attainment group who were ultra-high risk (77.35% vs. 92.06%, P＜0.001), female (16.24% vs. 23.08%, P=0.021), and those with comorbid hypertension (55.98% vs. 63.18%, P=0.038) was significantly lower than those in the LDL-C non-attainment group. Additionally, the baseline body mass index (BMI) [(25.37±3.24) kg/m2 vs. (26.03±3.56) kg/m2, P=0.017], total cholesterol levels [(3.30±0.84) mmol/L vs. (4.01±1.03) mmol/L, P＜0.001], LDL-C [(1.62±0.63) mmol/L vs. (2.25±0.85) mmol/L, P＜0.001], and high-density lipoprotein cholesterol [(0.98±0.26) mmol/L vs. (1.02±0.24) mmol/L, P=0.049] upon admission in the attainment group were all lower than those in the non-attainment group. Moreover, the lipid-lowering drug usage rate in the attainment group (100.00% vs. 96.24%, P=0.003) and the proportion using two types of drugs together (25.21% vs. 10.72%, P＜0.001) were both higher than those in the non-attainment group, while the statin monotherapy rate was lower than that in the non-attainment group (74.79% vs. 85.19%, P＜0.001). Logistic regression analysis showed that baseline BMI (OR=0.928, P=0.012) and baseline LDL-C levels (OR=0.207, P<0.001), patient cardiovascular risk stratification (OR=0.155, P<0.001) and lipid-lowering drug treatment regimen (OR=3.758, P<0.001) are significant factors affecting the LDL-C control status. Conclusion The LDL-C compliance rate of patients undergoing CABG is at a relatively low level 1 year after surgery. Patients with very high risk of atherosclerotic cardiovascular disease, high baseline LDL-C levels, and overweight or obesity should be strengthened lipid management. For these patients, the intensity of lipid-lowering drug use or combination medication should be increased upon discharge.

Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.