[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

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.

The theory of constitution in traditional Chinese medicine （TCM） has emerged as a new discipline in recent years. Constitution plays a vital role in the onset，progression，transformation，and prognosis of diseases. At present，some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation"，in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology，onset，pathogenesis，syndrome differentiation，and treatment. Against this background，the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution，aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models，thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions，diseases，and syndromes，but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods，the study evaluates the model's validity，reliability，and practicality，with the aim of opening new avenues for future research in TCM and promoting the development of the field.

In recent years, the prevalence of myopia has continued to rise, with an expanding affected population, making it a significant public health challenge both in China and globally. Elongation of the axial length in myopic eyes can induce a series of pathological changes in intraocular structure and function, increasing the risk of blinding ocular diseases such as retinal pathologies. Since myopia is difficult to reverse once established, scientific intervention is necessary to control its progression and reduce the likelihood of ocular complications. As a current research focus in myopia control, the clinical application of orthokeratology lenses has attracted considerable attention. This article highlights that orthokeratology lenses, worn overnight, reshape the corneal curvature and create a myopic defocus signal in the peripheral retina. This mechanism effectively inhibits excessive axial elongation and slows myopia progression. Clinical evidence indicates that orthokeratology can reduce axial elongation by 30% to 50%, accompanied by a short-term increase in choroidal thickness. This article also analyzes the advantages and limitations of orthokeratology and explores its potential synergistic effects when combined with other interventions such as low-dose atropine. The aim is to provide key theoretical and practical references for clinical myopia control.

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.

The theory of constitution in traditional Chinese medicine （TCM） has emerged as a new discipline in recent years. Constitution plays a vital role in the onset，progression，transformation，and prognosis of diseases. At present，some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation"，in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology，onset，pathogenesis，syndrome differentiation，and treatment. Against this background，the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution，aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models，thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions，diseases，and syndromes，but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods，the study evaluates the model's validity，reliability，and practicality，with the aim of opening new avenues for future research in TCM and promoting the development of the field.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

ObjectiveThe biosynthesis of heterophyllin B （HB）， a cyclopeptide from Pseudostellaria heterophylla， is regulated by various abiotic stresses. Elucidating the transcriptional regulatory mechanism underlying HB biosynthesis is of great guiding significance for the directional improvement of P. heterophylla varieties and the enhancement of HB content. MethodsBased on transcriptome data from different tissues of P. heterophylla， transcription factors （TFs） specifically upregulated and highly expressed in the phloem of tuberous roots were screened through a combination of Mfuzz time-series clustering， transcription factor family prediction， and correlation analysis. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to analyze expression patterns of candidate TFs under abscisic acid （ABA） induction， and the dual-luciferase reporter assay was applied to verify their regulatory effects on HB precursor genes. ResultsContent determination showed that HB accumulated at the highest in the phloem of P. heterophylla tuberous roots （34 μg·g^-1 fresh weight）. Transcriptome analysis identified 15 868 up-regulated differentially expressed genes （DEGs）， among which 4 375 were specifically up-regulated in the phloem. From these， 25 TFs highly expressed in the phloem were screened. Correlation analysis revealed that the expression level of WRKY70 was significantly positively correlated with HB content， the expression of precursor genes prePhHB， and PhPOP1. Additionally， WRKY70 expression was significantly upregulated under ABA induction. Dual-luciferase reporter assay confirmed that WRKY70 specifically activated the transcriptional activity of the prePhHB promoter （Pro-prePhHB）. ConclusionHB is mainly accumulated in the phloem of P. heterophylla tuberous roots. WRKY70 positively regulates HB biosynthesis by directly activating the promoter activity of prePhHB. This study clarifies the key role of WRKY70 in the regulation of HB biosynthesis and provides an important theoretical basis for the in-depth analysis of the molecular regulatory mechanism underlying HB biosynthesis.

OBJECTIVE To investigate the causal relationships between gut microbiota， blood metabolites and antidepressant treatment response from a genetic perspective， and to assess the potential mediating role of blood metabolites. METHODS This study utilized a two-sample Mendelian randomization （MR） design. Exposure data were derived from four large-scale gut microbiome genome-wide association study （GWAS） datasets and two blood metabolite GWAS datasets. The inverse variance weighted method was used as the primary method to evaluate the causal relationships between gut microbiota， blood metabolites and antidepressant effects. The robustness， heterogeneity and horizontal pleiotropy of the results were evaluated through various sensitivity analyses. Additionally， the false discovery rate （FDR） was applied to correct type Ⅰ errors caused by multiple hypothesis testing. Finally， MR mediation analysis was conducted to test the potential mediating effect of blood metabolites. RESULTS The s_ Bilophila was negatively associated with the effectiveness of antidepressant treatment （ P ＝8.030×10 －5 ， then P ＝0.033 after FDR correction）， and the f_Bacteroidales was positively associated with the effectiveness of antidepressant treatment （ P ＝3.275×10 －4 ， then P ＝0.034 after FDR correction）. Over a hundred blood metabolites were also screened out as being associated with antidepressant response， but after FDR correction， no significant causal relationship was observed. The P value of the mediation effect proportion of blood metabolites in the “gut microbiota-blood metabolites-antidepressant efficacy” pathway was greater than 0.05. CONCLUSIONS The s_ Bilophila may represent a risk factor for antidepressant effects， whereas the f_Bacteroidales may serve as a protective factor for antidepressant effects. The correlation between blood metabolites and antidepressant efficacy is not strong， and no genetic evidence is found to support that the investigated blood metabolites play a key mediating role between the gut microbiota and antidepressant response.

OBJECTIVE To study the clinical characteristics and potential risk factors for infection in patients with multiple myeloma （MM） following treatment with bortezomib. METHODS Clinical data were retrospectively collected from MM patients who received bortezomib-based treatment regimens at the Department of Hematology， the Second Affiliated Hospital of Soochow University， from October 2021 to February 2025. The collected data primarily included demographic characteristics， disease characteristics of MM， treatment regimens， occurrence of infections and corresponding management measures， and prophylactic medication use. Univariate and multivariate Logistic regression analyses were conducted to identify potential risk factors for MM complicated with infection. RESULTS Among the 284 MM patients treated with bortezomib， 132 patients （46.5%） experienced at least one infection. The predominant types of infections were respiratory tract infections and gastrointestinal infections. Univariate analysis showed that age at initial diagnosis， pathological classification， and grade of myelosuppression were influencing factors for infection in MM patients （ P ＜0.05）. Further analysis of influencing factors for the two main types of infections revealed that sex， age at initial diagnosis， pathological classification， treatment regimen， and smoking history were influencing factor s for respiratory tract infections in MM patients （ P ＜0.05）； BMI， pathological classification， treatment regimen， and grade of myelosuppression were influencing factors for gastrointestinal infections in MM patients （ P ＜0.05）. Multivariate Logistic regression analysis indicated that age≥70 years and the presence of grade Ⅳ myelosuppression before treatment were risk factors for infection in MM patients， while the IgG-λ type was a protective factor against infection （ P ＜0.05）. CONCLUSIONS The incidence of infection is relatively high in MM patients receiving bortezomib-based treatment regimens， with respiratory and gastrointestinal infections being the most common. Age at initial diagnosis， grade of myelosuppression， and pathological classification are influencing factors for infection in MM patients.