[摘 要] 目的：探究外周血1型辅助性T细胞（Th1）/Th2/Th17细胞相关细胞因子IL-2、IL-4、IL-6、IL-10、IFN-γ、TNF-α、IL-17A对Ⅲ~Ⅳ期肺鳞状细胞癌（LSCC）患者一线免疫治疗联合化疗疗效和预后的预测价值及其动态变化的意义。方法：回顾性分析2020年1月至2023年12月在内蒙古医科大学附属医院接受一线免疫治疗联合化疗的58例Ⅲ~Ⅳ期LSCC患者的临床资料，采集基线及治疗2、4、6周期后和疾病进展时的外周血，用流式细胞术检测Th1/Th2/Th17细胞分泌的细胞因子水平，用受试者工作特性曲线（ROC）确定各细胞因子基线的最佳截断值，据此将患者分为高、低表达组；根据RECIST 1.1标准，将患者分为客观缓解（ORR）[完全缓解（CR） + 部分缓解（PR）]组、非ORR[（疾病稳定（SD） + 疾病进展（PD）]组、疾病控制（DCR）（CR + PR + SD）组和非DCR（即PD）组；根据PD-L1表达评分将患者分为PD-L1 ≥ 1%组和PD-L1 < 1%或未知组。比较组间疗效的差异；分析临床病理特征与疗效的相关性；用广义估计方程（GEE）评估细胞因子动态变化与疗效的关系；用Kaplan-Meier法绘制生存曲线，Log-Rank检验比较组间差异，COX比例风险回归模型进行单因素及多因素预后分析。结果：IL-2和IFN-γ高表达组患者的客观缓解率（ORR）显著高于低表达组患者（P < 0.001）。IL-2、IFN-γ高表达组和IL-10、TNF-α低表达组患者的疾病控制率（DCR）均显著高于对应低/高表达组（P < 0.001）。PD-L1 ≥ 1%组DCR显著高于PD-L1 < 1%或未知组（P < 0.001）。动态分析显示，在4周期及6周期时，有效组患者血清中IL-6表达水平显著低于无效组（P < 0.05），控制组IL-6表达水平显著低于未控制组（P < 0.001）；治疗前及6周期时有效组IFN-γ表达水平显著高于无效组（P < 0.05），治疗前控制组IFN-γ表达水平显著高于未控制组（P < 0.05）。生存分析显示，IL-2低表达组、IL-10高表达组、TNF-α高表达组和IFN-γ低表达组患者的中位PFS显著缩短（均P < 0.05）。COX多因素分析证实，治疗前IL-2 < 2.45 pg/mL和IL-10 ≥ 3.52 pg/mL 是PFS的独立危险因素。结论：外周血Th1/Th2/Th17细胞相关细胞因子的基线水平及动态变化对Ⅲ~Ⅳ期LSCC患者一线免疫治疗联合化疗的疗效和预后具有预测价值。

ObjectiveHistorically documented Zhejiang Atractylodis Macrocephalae Rhizoma（Baizhu） possesses premium characteristics such as phoenix-like head and crane-like neck， pronounced sweetness， and fragrant aroma. However， its current market circulation is low， and the processed products with Zhejiang-style characteristics are at the risk of being lost. This study aims to preserve the ancient Zhejiang-style processing techniques and evaluate them using modern scientific methods. MethodsMultidimensional intelligent sensory evaluation was used to digitally characterize the "quality-structure" of the external appearance of nine-steamed and nine-processed Baizhu medicinal materials（intermediate processed products） and the "odor-taste" of the internal quality of its decoction pieces（slices）， and the appearance parameters were digitally characterized by colorimeter， texture analyzer， electronic nose and electronic tongue， the chemical composition was analyzed via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. Then， cluster analysis on the differences in odor between the medicinal materials（intermediate processed products） and decoction pieces（slices） of nine-steamed and nine-processed Baizhu was conducted， as well as the differences in taste between water-soluble and alcohol-soluble extracts of the decoction pieces（slices）， and the correlation analysis of chroma value-alcohol-soluble extract content-component response value. ResultsThe nine-steamed and nine-processed Baizhu had a dark brown to black epidermis， a brownish-yellow to brownish-gray cross-section， a slightly tough texture， a faint odor， and a slightly sweet， bitter and pungent taste. Texture analyzer measurements revealed minimal adhesion and maximum recovery in the middle section of the characteristic processed Baizhu， consistent with the processing endpoint of thorough steaming and cooking. The head section showed the highest internal hardness， elasticity and chewiness， indicating a denser texture in this area. The electronic nose sensor could clearly distinguish the difference between the medicinal materials and its decoction pieces， with a more significant clustering effect at 60 ℃ for 30 minutes compared to ambient temperature headspace for 2 hours， highlighting the significant impact of the baking degree before slicing on the quality. The electronic tongue taste signal map clearly distinguished the differences between water-soluble and alcohol-soluble extracts of nine-steamed and nine-processed Baizhu decoction pieces， and the addition of auxiliary materials during processing could enhance its alcohol-soluble extract content. A total of 82 chemical components were identified in the characteristic processed Baizhu. After processing， the contents of 58 components increased， while 24 components decreased. Correlation analysis revealed significant negative correlations（P<0.01） between ethanol-soluble extract content and colorimetric values of brightness（L^*）， yellow-bule value（b^*）， and total color difference（E^*_ab）. E^*_ab showed marked negative correlations（P<0.05） with the response values of isochlorogenic acid A and C. ConclusionThis study establishes a modern intelligent sensory evaluation model for multidimensional holographic characterization of nine-steamed and nine-processed Baizhu， clarifying the correlation between increased isochlorogenic acid content and the visual color appearance after different steaming cycles， as well as its intrinsic alcohol-soluble extracts. This provides a reference for quality evaluation and processing standards of the Zhejiang-style characteristic processed products.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

Dendrobium officinale(DO) is a traditional Chinese medicinal and edible plant, while it is critically endangered worldwide. This article, primarily based on the original research findings of the author's team and available articles, provides a comprehensive overview of the factors contributing to the endangerment of DO and the key technologies for the conservation, efficient cultivation, and value-added utilization of this plant. The scarcity of wild populations, low seed-setting rates, lack of endosperm in seeds, and the need for symbiosis with endophytic fungi for seed germination under natural conditions are identified as the primary causes for the rarity and endangerment of DO. Artificial seed production and tissue culture are highlighted as key technologies for alleviating the endangered status. The physiological and ecological mechanisms underlying the adaptation of DO to epiphytic growth are explored, and it is proposed that breaking the coupling of high temperature and high humidity is essential for preventing southern blight, a devastating affliction of DO. The roles of endophytic fungi in promoting the growth, improving the quality, and enhancing the stress resistance of DO are discussed. Furthermore, the integration of variety breeding, environment selection, and co-culture with endophytic fungi is emphasized as a crucial approach for efficient cultivation. The value-added applications of DO in pharmaceuticals, health foods, food products, and daily chemicals-particularly in the food and daily chemical industries-are presented as key drivers for a 10-billion-RMB-level industry. This systematic review offers valuable insights for the further development, utilization, and industrialization of DO resources, as well as for the broader application of conservation strategies for other rare and endangered plant species.
Dendrobium/microbiology* ; Endangered Species ; Seeds/microbiology* ; Fungi/physiology*

The AP2/ERF transcription factor family is a class of transcription factors widely present in plants, playing a crucial role in regulating flowering, flower development, flower opening, and flower senescence. Based on transcriptome data from flower, leaf, and stem samples of two Lonicera macranthoides varieties, 117 L. macranthoides AP2/ERF family members were identified, including 14 AP2 subfamily members, 61 ERF subfamily members, 40 DREB subfamily members, and 2 RAV subfamily members. Bioinformatics and differential gene expression analyses were performed using NCBI, ExPASy, SOMPA, and other platforms, and the expression patterns of L. macranthoides AP2/ERF transcription factors were validated via qRT-PCR. The results indicated that the 117 LmAP2/ERF members exhibited both similarities and variations in protein physicochemical properties, AP2 domains, family evolution, and protein functions. Differential gene expression analysis revealed that AP2/ERF transcription factors were primarily differentially expressed in the flowers of the two L. macranthoides varieties, with the differentially expressed genes mainly belonging to the ERF and DREB subfamilies. Further analysis identified three AP2 subfamily genes and two ERF subfamily genes as potential regulators of flower development, two ERF subfamily genes involved in flower opening, and two ERF subfamily genes along with one DREB subfamily gene involved in flower senescence. Based on family evolution and expression analyses, it is speculated that AP2/ERF transcription factors can regulate flower development, opening, and senescence in L. macranthoides, with ERF subfamily genes potentially serving as key regulators of flowering duration. These findings provide a theoretical foundation for further research into the specific functions of the AP2/ERF transcription factor family in L. macranthoides and offer important theoretical insights into the molecular mechanisms underlying floral phenotypic differences among its varieties.
Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Transcription Factors/chemistry* ; Lonicera/classification* ; Flowers/metabolism* ; Phylogeny ; Gene Expression Profiling ; Multigene Family

PURPOSE: Although there are significant differences between China and the United States (US) in trauma medical services, there has been no direct comparative research on the epidemiological data of trauma centers between the 2 countries. This study aims to fill this research gap by directly comparing trauma centers in China and the US, providing valuable data and insights for the development of trauma centers in both countries, promoting academic exchange and cooperation internationally, and enhancing the level of global trauma medical care. METHODS: This is a multicenter retrospective descriptive study. Data were collected for trauma patients with an injury severity score ≥16 treated from September 2013 to September 2019 at 2 hospital trauma centers in these 2 countries. Detailed clinical data (including injury mechanism, age, injury site, injury severity score, pre-hospital transport time, whether blood transfusion was performed, whether resuscitative thoracotomy was conducted, hospital and intensive care unit stay duration, the number of organ donor patients, mortality rates, and costs) were meticulously compiled and retrospectively analyzed to identify differences between the 2 trauma centers. The comparison was conducted using SPSS 23 software. Continuous variables are reported as median (Q₁, Q₃), and Mann Whitney U test is used to compare the median of continuous variables. Use clinically relevant critical points to classify continuous variables, with categorical variables represented as n (%), and comparisons were made between the 2 groups using the χ² test or Fisher's exact test. Statistical significance was defined as a 2-sided p < 0.05. RESULTS: These results point to significant differences in trauma center capacity, pre-hospital transport times, treatment procedures, hospital stay duration, mortality rates, and costs between the 2 centers. The volume of patients in trauma centers is less in China (2465 vs. 5288). Pre-hospital transport time was notably longer in China (180 min vs. 14 min), and the rate of emergency blood transfusions was lower in China (18.4% vs. 50.6%), Emergency thoracotomy was not performed in China but was conducted in 9.8% of cases in the US. Hospitalization costs were significantly lower in China than in the US ($5847 vs. $75,671). CONCLUSION There are clear differences in trauma center capacity (number of patients treated), pre-hospital transport time, age distribution of injured patients, injury mechanisms, injury sites, whether emergency thoracotomy is performed, hospital costs, and length of stay between the 2 trauma centers in China and America. Understanding these differences can help us further recognize the characteristics of Eastern and Western trauma patients.
Humans ; China/epidemiology* ; Trauma Centers/statistics & numerical data* ; Retrospective Studies ; United States/epidemiology* ; Male ; Female ; Wounds and Injuries/therapy* ; Middle Aged ; Adult ; Injury Severity Score ; Length of Stay/statistics & numerical data* ; Treatment Outcome

OBJECTIVE: To analyze the distribution characteristics of glucose-6-phosphate-dehydrogenase (G6PD) mutations and their enzyme activity in newborns patients with G6PD deficiency in Guilin region. METHODS: From July 2022 to July 2024, umbilical cord blood samples from 4 554 newborns in Guilin were analyzed for G6PD mutations using fluorescence PCR melting curve analysis. Enzyme activity was detected in 4 467 cases using the rate assay. RESULTS: Among 4 467 newborns who underwent G6PD activity testing, 162 newborns (3.63%) were identified as G6PD-deficient, including 142 males (6.04%) and 20 females (0.94%), the prevalence of G6PD deficiency was significantly higher in males than in females (P < 0.001). Genetic analysis of 4 554 newborns detected G6PD mutations in 410 cases (9%), including 171 males (7.13%) and 239 females (11.09%), with a significantly higher mutation detection rate in females than in males (P < 0.001). A total of nine single mutations and four compound heterozygous mutations were identified. The most common mutations were c.1388G>A (33.66%), c.1376G>T (23.66%) and c.95A>G (16.34%). Among newborns who underwent both enzyme activity and genetic mutation testing, males with G6PD mutations had significantly lower enzyme activity than that of females with G6PD mutations(P < 0.001). Specifically, among newborns carrying the mutations c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T or c.871G>A, males consistently exhibited lower enzymatic activity than females with the same mutations (P < 0.001). Furthermore, in male G6PD-deficient newborns, the enzyme activity levels in those carrying c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T, or c.871G>A were lower than those in both the control group and the c.519C>T group (P < 0.05). CONCLUSION This study provides a comprehensive profile of G6PD deficiency incidence and mutation spectrum in the Guilin region. By analyzing enzyme activity and genetic mutation results, this study provides insights into potential intervention strategies and personalized management approaches for the prevention and treatment of neonatal G6PD deficiency in the region.
Humans ; Infant, Newborn ; Glucosephosphate Dehydrogenase Deficiency/epidemiology* ; Glucosephosphate Dehydrogenase/genetics* ; Female ; Male ; Mutation ; China/epidemiology*

OBJECTIVE: To investigate the molecular alterations of splenocytes associated with anti-factor Ⅷ (FⅧ) immune response and the underlying mechanisms based on hemophilia A (HA) murine model via RNA sequencing (RNA-seq) technology. METHODS: Severe HA mice were immunized with recombinant human factor Ⅷ (rhF8) weekly for 4 weeks to establish an FⅧ inhibitor model. High quality raw data were obtained by using bulk RNA-seq and CASAVA base identification technology, and the differentially expressed genes (DEGs) were identified. The DEGs were statistically classified by gene ontology (GO) annotation to obtain information on the major signaling pathways and biological processes involved in anti-FⅧ immune response in HA mouse splenocytes. The cell clusters, genes, and signaling pathway datasets were comprehensively analyzed by GO, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and single cell RNA-seq (ScRNA-seq) analysis, respectively. Flow cytometry analysis was used to verify the changes in T follicular helper cells (Tfh) and regulatory T cells (Treg). RESULTS: A total of 3731 DEGs was identified, including 2275 genes with up-regulated expression and 1456 genes with down-regulated expression. The DEGs were enriched in helper T cell differentiation, cytokine receptor, T cell receptor signaling pathway, ferroptosis, etc. Uniform Manifold Approximation and Project (UMAP) downscaling and visualization analysis yielded a total number of 11 T/NK cell subsets, visualizing the overall expression distribution of C-X-C chemokine-specific receptor gene cxcr5 among these T/NK cell subsets. Higher expression of cxcr5 was found in activated Tfh from FⅧ inhibitor mice, in comparison to the control group. The visualization using Upset plot R language showed a close interaction between Tfh and Treg. Moreover, the increased frequencies of Tfh and the decreased frequencies of Treg in inhibitor mouse splenocytes were further verified by flow cytometry analysis. CONCLUSION Multiple immune cell subsets, signaling pathways, and characteristic genes may be involved in the process of anti-FⅧ immune response in HA mouse splenocytes. The molecules involved in the regulation of Tfh/Treg may play key roles, which provide potential biological targets and therapeutic strategies for HA patients with inhibitors in the future.
Animals ; Hemophilia A/genetics* ; Mice ; Sequence Analysis, RNA ; Disease Models, Animal ; Spleen/cytology* ; T-Lymphocytes, Regulatory/immunology* ; Humans ; Signal Transduction ; Factor VIII/immunology* ; T-Lymphocytes, Helper-Inducer/immunology*

BACKGROUND: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5. METHODS: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients. RESULTS: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels. CONCLUSIONS A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Cardiovascular Diseases/blood* ; Male ; Female ; Middle Aged ; C-Reactive Protein/metabolism* ; Aged ; Biomarkers/blood* ; Nutrition Surveys ; Adult ; United States/epidemiology* ; Serum Albumin/analysis*