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.

OBJECTIVE To evaluate the anticoagulant efficacy and safety of nafamostat mesylate （NM） in the treatment of uremic patients at high risk of bleeding undergoing continuous veno-venous hemofiltration （CVVH） with different methods （pre- dilution and post-dilution）. METHODS A total of 130 uremic patients at high risk of bleeding who underwent CVVH treatment in the nephrology department of Chongqing University Three Gorges Hospital from July 2023 to September 2024 were selected. They were divided into pre-dilution group and post-dilution group according to the random number table method， with 65 cases in each group. Both groups of patients received CVVH treatment under NM anticoagulation. The pre-dilution group adopted the pre-dilution replacement method， while the post-dilution group adopted the post-dilution replacement method. The coagulation， pressure， and usage duration of the filter and dialysis circuit venous reservoirs were compared between the two groups. The changes in prothrombin time （PT）， prothrombin time-international normalized ratio （PT-INR）， activated partial thromboplastin time （APTT）， and fibrinogen （FIB） in the peripheral venous blood before the heparin pump and after the filter at 1， 4 and 7 h of CVVH treatment， as well as 20 min after the end of treatment， were compared between the two groups. The single-compartment urea clearance rate （spKt/V）， β2-microglobulin （β2-MG） clearance rate and the incidence of adverse reactions were duni2007@foxmail.com compared between the two groups. RESULTS Both the pre-dilution and post-dilution groups had 60 patients who completed the study. The incidence of grade Ⅱ-Ⅲ coagulation of the filter and venous reservoirs， as well as the number of patients with transmembrane and venous pressure alarm intervention in the post- dilution group were significantly higher or more than those in the pre-dilution group （P＜0.05）， while usage time of the filter and the pipeline in the post-dilution group was significantly shorter than that in the pre-dilution group （P＜0.05）. The APTT values before the heparin pump as well as PT and APTT values after the filter at 1 h， 4 h， and 7 h of CVVH treatment in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There were no significant differences in PT， PT- INR， APTT and FIB between the two groups of patients 20 min after the end of treatment （P＞0.05）. The spKt/v and β2-MG clearance rates in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS When NM is used as an anticoagulant in the CVVH treatment of uremic patients at high risk of bleeding， compared with the pre-dilution treatment method， the post-dilution treatment method has a higher incidence of filter and dialysis tubing venous reservoir， a shorter usage time of the filter and pipeline， and a greater impact on extracorporeal coagulation， but has a higher solute clearance rate. Clinically， different dilution methods can be selected according to the different treatment needs of patients.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.