[摘 要] 目的：探讨干扰素刺激基因家族成员黏病毒抵抗蛋白2（MX2）在调控肿瘤细胞对呼肠孤病毒（Reo）溶瘤敏感性中的作用及其机制。方法：选取4株具有不同耐药特征的人源肿瘤细胞，通过CCK-8法评估其对Reo的溶瘤敏感性；通过转录组测序筛选出差异表达基因MX2，qPCR法及WB法验证MX2在4株人源肿瘤细胞中的表达；使用siRNA敲低溶瘤低敏感的COC1/DDP细胞中的MX2基因。在细胞感染Reo病毒后，通过CCK-8法检测细胞存活率；qPCR法检测细胞中Reo病毒S1基因表达；免疫荧光法检测细胞内Reo病毒蛋白的积累；半数组织培养感染剂量（TCID50）法测定病毒滴度；流式细胞术分别检测细胞内Reo病毒dsRNA、活性氧（ROS）水平以及细胞凋亡率；透射电镜观察细胞内质网形态变化并采用WB法检测内质网应激相关蛋白（JNK、p-JNK、eIF2α、p-eIF2α、CHOP、PERK）的表达。结果：在4株肿瘤细胞中，SKOV3细胞对Reo溶瘤作用高度敏感，而COC1/DDP、HuH-7SRB及SNU-398细胞均为溶瘤低敏感性。转录组测序结果显示，MX2在溶瘤低敏感肿瘤细胞中的表达水平显著高于溶瘤高敏感细胞（P < 0.01）；在溶瘤低敏感性的COC1/DDP细胞中，敲低MX2显著促进Reo病毒复制、诱导细胞凋亡增加，并升高细胞内活性氧水平（均P < 0.001）。透射电镜观察显示，敲低MX2的COC1/DDP细胞感染Reo病毒后出现内质网肿胀、扩张及断裂等典型内质网应激超微结构改变。WB结果显示，内质网应激关键标志物eIF2α/p-eIF2α、PERK、CHOP及凋亡相关调节蛋白JNK/p-JNK的表达均显著上调（P < 0.05或P < 0.01）。结论：肿瘤细胞对Reo的溶瘤敏感性与其细胞内MX2表达水平密切相关。敲低MX2可显著增强Reo在细胞内的复制，进而促进ROS积累，触发内质网应激并促进凋亡。病毒复制增加与细胞凋亡激活的双重作用，最终协同增强Reo的溶瘤作用。

Objective To investigate the prognostic value of preoperative plasma fibrinogen (FIB) combined with lymphocyte-to-monocyte ratio (LMR) in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Methods A retrospective analysis was conducted on ESCC patients who underwent esophagectomy in the Affiliated Lihuili Hospital of Ningbo University from 2015 to 2018. Based on the cut-off values of preoperative FIB and LMR, the F-LMR scoring system was constructed, and patients were divided into three groups according to the F-LMR score. Kaplan-Meier analysis was used to assess 5-year overall survival (OS) and 5-year progression free survival (PFS), and univariate and multivariate Cox regression analyses were performed to identify prognostic factors. Results Finally 260 patients were collected, including 237 males and 23 females, with a median age of 64 years (IQR: 59-70). The 5-year OS rates for patients with F-LMR score of 0, 1, and 2 were 24.44%, 51.69%, and 67.31%, respectively, and the 5-year PFS rates were 15.56%, 42.37%, and 57.62%, respectively. Lower preoperative F-LMR scores were associated with worse prognosis. Multivariate analysis showed that deeper tumor invasion, presence of lymph node metastasis, larger tumor maximum diameter, and lower preoperative F-LMR score were independent risk factors for OS. Conclusion The F-LMR scoring system based on the preoperative FIB and LMR may serve as an effective tool for predicting the prognosis of patients with ESCC.

In the context of the modernization of traditional Chinese medicine （TCM）， the inheritance of the experiences of famous doctors faces significant challenges due to its complex nonlinear characteristics and dynamic evolution. There are still issues in the current inheritance system， such as the homogenization of talent cultivation models， lack of standardized mentoring practices， and monotonous evaluation method， which hinder the systematic inheritance and innovative development of famous doctors' experiences. Based on a systematic review of the current state of artificial intelligence （AI）-assisted inheritance of famous doctors' experiences， this study explores innovative pathways for deep integration of modern information technologies with famous doctors' experiences from key dimensions， including data authenticity assurance， interdisciplinary collaboration mechanisms， and the establishment of dynamic inheritance standards. It proposes a paradigm shift in the inheritance of TCM famous doctors' experiences in the AI era， aiming to build a new TCM inheritance system of "digital intelligence empowerment and cross-disciplinary innovation"， providing theoretical support and practical pathways for the inheritance of famous doctors' experiences in TCM.

ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

In recent years， traditional Chinese medicine （TCM） has achieved significant progress in the treatment of inflammatory bowel disease （IBD）. A comprehensive literature search was conducted covering the period from January 1， 2010， to December 30， 2024， across Chinese databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP China Science and Technology Journal Database， and the Chinese Biomedical Literature Service System， as well as international databases such as PubMed， Web of Science， and Embase. The clinical applications and mechanistic studies of TCM in IBD were systematically reviewed. The current status of TCM research on the etiology and pathogenesis of IBD， innovative clinical practices， and multimodal therapeutic approaches， including Chinese herbal formulas， single herbs or active compounds， acupuncture， herbal retention enema， and acupoint application， were summarized， together with their synergistic effects when combined with western medical treatments. The development and application of Chinese patent medicines for IBD are undergoing a profound transition from efficacy validation to mechanistic exploration. Mechanistic studies on the effects of TCM in IBD mainly focus on regulating gut microbiota homeostasis， repairing the intestinal mucosal barrier， and modulating intestinal immune balance. Furthermore， future research directions for TCM-based IBD management are proposed， including the establishment of TCM diagnostic and treatment models， expanding integrated applications of external and internal TCM therapies， innovating personalized treatment strategies， and advancing drug development. These efforts aim to provide insights for the standardized and precision-oriented development of TCM in the diagnosis and treatment of IBD.

OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

OBJECTIVE To explore a model for constructing a platform for medical institution formulation and provide insights for promoting their development. METHODS By systematically reviewing the development status and challenges of medical institution preparations in China， and based on the theory of industry-university-research collaborative innovation， the organizational structure， collaborative processes， and safeguard mechanisms of the platform were designed. RESULTS & CONCLUSIONS Medical institution formulations in China mainly faced challenges such as weak research and development （R&D） capacity， uneven quality standards， and blocked transformation pathways. This study established a full-chain， whole- industry collaborative innovation network covering the government， medical institutions， universities/research institutes， pharmaceutical enterprises， and the market， forming a new “government-industry-university-research-application” five-in-one platform model for medical institution formulations. By establishing mechanisms such as multi-entity collaborative cooperation， full- chain intellectual property management， contribution-based benefit distribution， staged risk-sharing， and third-party evaluation， the model clarified the responsibilities and collaborative pathways of all parties. The new model highlights the whole-process transformation of clinical experience-based prescriptions， enabling precise alignment between clinical needs and technological R&D， as well as between preparation achievements and industrial transformation. While breaking down the barriers of traditional platform construction， it effectively achieves optimal resource allocation and complementary advantages， addresses problems emerging in the development of medical institution preparations， and provides reference value for the formulation of relevant systems.

ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×10⁹/L vs （192.82±44.13）×10⁹/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）. ConclusionFor ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

ObjectiveTo investigate the effects of Yueju Wan on the 5-hydroxytryptamine （5-HT） signaling pathway in rats with functional dyspepsia （FD） and to explore its therapeutic mechanism in the treatment of FD. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， model group， mosapride group （1.575 mg·kg^-1）， and Yueju Wan low-， medium-， and high-dose groups （0.735， 1.47， and 2.94 g·kg^-1， respectively）. The FD rat model was established using GUO's tail-clamping stimulation combined with irregular feeding. After 14 days of modeling， rats were administered the corresponding drugs by gavage for 28 days. After treatment， gastric emptying rate and small intestinal propulsion rate were measured. Serum levels of 5-HT， tryptophan hydroxylase （TPH）， and substance P （SP） were detected by enzyme-linked immunosorbent assay （ELISA）， and acetylcholine （ACh） levels were determined by chemical methods. Histopathological changes in the gastric antrum were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to assess the mRNA and protein expression levels of 5-hydroxytryptamine 4 receptor （5-HT4R）， SP， and acetylcholinesterase （AChE） in colon tissue， as well as 5-hydroxytryptamine 3 receptor （5-HT3R）， SP， and AChE in hypothalamic tissue. Immunohistochemistry （IHC） was used to examine the expression of 5-HT and 5-HT4R in the colon and 5-HT and 5-HT3R in the hypothalamus. ResultsCompared with the normal group， the gastric emptying rate and small intestinal propulsion rate in the model group were significantly decreased （P<0.01）. Serum levels of 5-HT， SP， ACh， and TPH were significantly reduced （P<0.01）. Histopathological examination revealed irregular arrangement of glands in the gastric antrum， slight mucosal atrophy， and mild inflammatory cell infiltration. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue， as well as 5-HT3R， SP， and AChE in hypothalamic tissue， were significantly decreased （P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was also significantly reduced （P<0.01）. Compared with the model group， all Yueju Wan groups showed significantly increased gastric emptying rate and small intestinal propulsion rate （P<0.01）. The glands in the gastric antrum were more regularly arranged， with no inflammatory cell infiltration observed. Serum levels of 5-HT， SP， ACh， and TPH were significantly increased （P<0.01）. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue and 5-HT3R， SP， and AChE in hypothalamic tissue were significantly upregulated （P<0.05， P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was significantly increased （P<0.01）. ConclusionYueju Wan has preventive and therapeutic effects on FD， and its mechanism may be related to regulation of the 5-HT signaling pathway， promotion of brain-gut peptide secretion， and enhancement of gastric motility.

OBJECTIVE To clarify the roles and functions of full-time pharmacists in the management of early-phase clinical trials of antineoplastic drugs， and to provide theoretical and practical support for their transformation from traditional drug managers to multi-dimensional roles in clinical research. METHODS Combined with relevant regulations such as the Good Clinical Practice （GCP） （2020 Edition）， and based on the clinical practice experience of the Phase Ⅰ Clinical Ward in our hospital， this study systematically sorted out full-time pharmacists’ roles and functions in early-phase clinical trials of antineoplastic drugs， and explored the core challenges and optimization pathways for role transformation and capacity-building of domestic full-time clinical trial pharmacists. RESULTS & CONCLUSIONS Full-time pharmacists assumed multiple roles in early-phase clinical trials of antineoplastic drugs， including providing pharmaceutical support for protocol design， implementing whole-process standardized management of clinical trial drugs， ensuring medication safety for clinical trial subjects/participants， conducting quality control throughout the clinical trial process， and serving as a bridge for interdisciplinary collaboration and communication. Currently， there are challenges in this field in China， such as unclear roles， an imperfect capacity building system， and insufficient regulatory support. This paper proposes that by establishing a standardized role framework， clarifying the core responsibilities and authorities of full-time pharmacists， and leveraging cutting-edge technologies to provide comprehensive support for their roles， so as to fully harness their pharmaceutical expertise and contribute to the standardization and efficiency of the antineoplastic new drug development process.