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.

ObjectiveTo explore the typical syndromes and their characteristic of symptoms and signs with high diagnostic value in patients with metabolic syndrome （MS）. MethodsTraditional Chinese medicine （TCM） diagnostic information was collected from 135 MS patients. Syndrome element differentiation and latent class analysis （LCA） were applied to identify the major TCM syndromes in MS patients. Symptoms were analyzed based on the differentiated syndromes， and a binary logistic regression model was constructed to determine symptoms and signs with high diagnostic value. ResultsA total of 135 MS patients were included， involving 163 symptoms and signs with a total frequency of 1749； twenty-three syndrome elements were extracted， 367 times frequency in total， among which 8 syndrome elements occurred ≥10 times with 323 frequencies （88.01% of the total）. These included location-related elements such as kidney （48 times）， spleen （14 times）， and stomach （14 times）， and nature-related elements such as phlegm （71 times）， yin deficiency （64 times）， dampness （57 times）， heat （42 times）， and qi deficiency （13 times）. Based on LCA， the 135 patients were categorized into two groups distinguished by the syndrome elements of dampness and phlegm， forming the "phlegm-dampness syndrome" as the major syndrome type. Nine high-frequency symptoms and signs associated with the phlegm-dampness syndrome were identified，i.e. obesity （39 times）， greasy coating （38 times）， slippery pulse （33 times）， white coating （31 times）， preference for fatty and heavy foods （30 times）， excessive urination （30 times）， fatigue and lack of strength （29 times）， wiry pulse （25 times）， and dark red tongue （25 times）. A binary logistic regression model was constructed combining these nine symptoms and signs with the LCA classification results， ultimately identifying obesity， greasy coating， fatigue and lack of strength， and white coating as independent factors associated with the phlegm-dampness syndrome in MS patients （P＜0.05）. ConclusionThe major TCM syndrome in MS patients is phlegm-dampness syndrome， and obesity， greasy coating， fatigue and lack of strength， and white coating are the typical symptoms and signs for diagnosing phlegm-dampness syndrome in MS patients.

ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer （CRC） and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit， followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group， low-dose Xianlian Jiedu prescription （XLJDP-L） group （6.45 g·kg^-1·d^-1）， medium-dose Xianlian Jiedu prescription （XLJDP-M） group （12.9 g·kg^-1·d^-1）， high-dose Xianlian Jiedu prescription （XLJDP-H） group （25.8 g·kg^-1·d^-1）， and 5-fluorouracil （5-FU） group （1×10^-3 g·kg^-1·d^-1）. The mice were euthanized after 14 days of continuous intervention， and recurrent tumor tissue was harvested. Hematoxylin and eosin （HE） staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry （IHC） was employed to assess the expression of proliferating cell nuclear antigen （Ki67）， vascular endothelial growth factor （VEGF）， and platelet-endothelial cell adhesion molecule （CD31） in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 （ANG-2）， VEGF， phosphorylated-protein kinase B （p-Akt）， protein kinase B （Akt）， phosphorylated-phosphatidylinositol 3-kinase （p-PI3K）， and phosphatidylinositol 3-kinase （PI3K） in recurrent tumor tissue. ResultsBefore treatment， there were no statistical differences in tumor volume， tumor weight， and body mass among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group， indicating model stability. After treatment， compared with those in the model group， the tumor volume and tumor weight in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01）， showing dose dependency. Meanwhile， there were no significant differences in body weight among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group， tumor tissue in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group had loosely arranged cells， increased intercellular spaces， small and shriveled nuclei， light staining， fewer mitotic figures and atypical nuclei， and increased necrotic areas. IHC showed that compared with those of the model group， the positive rates of Ki67， VEGF， and CD31 in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01） in a dose-dependent manner. Western blot results showed that compared with those of the model group， the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly downregulated （P<0.05， P<0.01）， and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner （P<0.05， P<0.01）. ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2， VEGF， and CD31.

As a patented characteristic medicine of Yi ethnic minority， Pingxuan capsules have the effects of nourishing the liver and kidney， pacifying the liver， and subduing Yang. With the main indications of dizziness， headache， palpitations， tinnitus， insomnia， dreaminess， waist and knee soreness caused by liver-kidney deficiency and liver Yang upward disturbance， Pingxuan capsules are widely used in the treatment of posterior circulation ischemic vertigo， vestibular migraine， benign paroxysmal positional vertigo. However， the current knowledge is limited regarding the efficacy， syndrome differentiation， and safety of this medicine. On the basis of summarizing the experience of clinicians and the existing evidence， this study invites clinical experts of traditional Chinese and Western medicine， pharmaceutical experts， and methodological experts from relevant fields across China to conduct evidence-based evaluation of Pingxuan capsules. The evaluation follows the Specifications for the Development of Clinical Expert Consensus on Chinese Patent Medicines issued by the Standardization Office of the China Association of Chinese Medicine， and reaches 5 recommendations and 16 consensus suggestions. The consensus clarifies the clinical applications， efficacy， dose， course of treatment， combination of medicines， precautions， and contraindications of Pingxuan capsules in the treatment of vertigo and explains the safety of clinical application. This consensus is applicable to clinicians （traditional Chinese medicine， Western medicine， and integrated traditional Chinese and Western medicine） and pharmacists in tertiary hospitals， secondary hospitals， and community-level medical and health institutions across China， providing a reference for the rational use of Pingxuan capsules in the treatment of vertigo. It is hoped that the promotion of this consensus can facilitate the rational use of drugs in clinical practice， reduce the risk of drug use， and give full play to the advantages of Pingxuan capsules in the treatment of vertigo diseases. This consensus has been reviewed and published by the China Association of Chinese Medicine， with the number GS/CACM330-2023.

ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

ObjectiveTo explore the effect of modified Ditan Decoction （涤痰汤） on chronic intermittent hypoxia cognitive function and the potential function mechanism. MethodsTwenty-four Sprague-Dawley （SD） rats were randomly divided into a normal group， a model group， and a modified Ditan Decoction group， with eight rats in each group. Rats in the modified Ditan Decoction group were administered the decoction by gavage at 14.8 ml/（kg·d）， while the normal group and the model group received the same dose of normal saline. Thirty minutes after daily gavage， the rats in all three groups were placed in an intermittent hypoxia chamber. The oxygen concentration for the model group and the modified Ditan Decoction group was adjusted daily for 8 hours using a computer program to establish the model， while the normal group was exposed to the same airflow rate of ambient air. The intervention was continued for 12 weeks to establish a chronic intermittent hypoxia rat model. The Y-maze test was used to evaluate spatial working memory in the rats. Resting-state functional magnetic resonance imaging （rs-fMRI） was performed to detect whole-brain regional homogeneity （ReHo） and seed-based functional connectivity （FC）. Brain regions showing significant differences in rs-fMRI were selected for further analysis. Immunofluorescence was used to detect β-amyloid （Aβ） deposition and the number of ionized calcium-binding adapter molecule 1 （IBA1）-positive microglial cells. Immunohistochemistry was employed to assess the expression of synaptophysin （SYP）， the excitatory synapse marker vesicular glutamate transporter 1 （Vglut1）， and the inhibitory synapse marker vesicular γ-aminobutyric acid transporter （VGAT）. ResultsCompared with the normal group， the model group showed a reduced spontaneous alternation rate in the Y-maze test. The smoothed Z-score standardized regional homogeneity （SzReHo） value in the left entorhinal cortex significantly increased， and the FC value from this seed point to the left basal forebrain significantly reduced. Additionally， the model group exhibited significantly higher Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex， decreased expression of SYP， Vglut1， and VGAT， along with an increased Vglut1/VGAT ratio （P＜0.05 or P＜0.01）. Compared to the model group， the modified Ditan Decoction group demonstrated an increased spontaneous alternation rate， a significantly reduced SzReHo value in the left entorhinal cortex， and a significantly increased FC value from this region to the left basal forebrain. Furthermore， this group showed significantly lower Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex， increased levels of SYP， Vglut1， and VGAT， and a decreased Vglut1/VGAT ratio （P＜0.05 or P＜0.01）. ConclusionModified Ditan Decoction can reconstruct the projection from the left basal forebrain to the entorhinal cortex in chronic intermittent hypoxia， thereby reducing Aβ aggregation and excessive microglial activation in the left entorhinal cortex. This process improves the excitation/inhibition imbalance caused by synaptic remodeling， ultimately enhancing cognitive function in rats of chronic intermittent hypoxia.

OBJECTIVE To investigate the use of drugs and the development of pharmaceutical care in the tight medical alliance （shorted for “medical alliance”） of Wanzhou District of Chongqing， and provide reference for the further construction of the medical alliance. METHODS A survey form was designed and distributed to 21 constituent units （5 leading units and 16 member units） of 5 medical alliances in Wanzhou District of Chongqing. The statistical analysis was conducted in aspects of basic drug allocation and use， pharmaceutical personnel team construction， the development of pharmaceutical care， and rational use of antibiotics. RESULTS Among the 21 constituent units， 4 leading units and 14 member units achieved the target for the proportion of essential drug procurement varieties， with a total compliance rate of 85.71%； 4 leading units and 13 member units achieved the target for the proportion of national essential drug allocation and usage amount， with a total compliance rate of 80.95%. The proportions of personnel with doctoral degrees in the 5 leading units and 16 member units were 1.71% and 0 respectively， and the proportions of personnel with senior professional titles were 8.56% and 1.63%， respectively. A total of 5 pharmacy or pharmaceutical combined outpatient clinics were set up in the 21 medical alliance units， and 5 clinical pharmacy information service platforms were established； all 5 leading units were able to regularly carry out clinical pharmacy projects， while only 4 out of 16 member units had conducted medical order review and evaluation. The proportions of irrational use of antibiotics in outpatient prescriptions and inpatient medical records of the 16 member units （4.81%， 5.21%） were significantly higher than those of the 5 leading units （2.80%， 4.00%）. CONCLUSIONS The allocation and usage of national essential drugs in 21 constituent units from Wanzhou District of Chongqing are both in good standing. However， the data on the allocation of pharmaceutical professionals and the number， qualifications， and job titles of clinical pharmacists in member units are generally low. Moreover， the pharmaceutical service projects and service quality in member units need to be further improved.

Tacrolimus is a crucial therapeutic drug for preventing immune rejection after solid organ transplantation in children. Due to the narrow treatment window and significant individual variability， personalized treatment is often required. In recent years， with the promotion of therapeutic drug monitoring technology， individualized treatment models based on tacrolimus drug concentration have developed rapidly. This article reviews the research progress of individualized dosing models for tacrolimus in children both domestically and internationally over the past decade. It includes dose simulation methods based on population pharmacokinetics， physiologically based pharmacokinetics， machine learning， and multiple linear regression. The characteristics of each model and its application in pediatric individualized dosing are analyzed and summarized. Additionally， the current development status of decision support systems for individualized tacrolimus dosing is introduced.