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.

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.

ObjectiveTo investigate the regulatory effects and underlying mechanisms of Liuhuang Zhike prescription （LHZK） on blood glucose in type 2 diabetic db/db mice based on the AMP-activated protein kinase/protein kinase B/glycogen synthase kinase-3β （AMPK/Akt/GSK-3β） signaling pathway. MethodsDb/db mice were used as the model animals， and db/m mice served as the blank control. Forty db/db mice were randomly divided into the model group， metformin group （0.14 g·kg^-1）， and low-， medium-， and high-dose （4.11， 8.21， 16.43 g·kg^-1） LHZK groups， with 8 mice in each group. The db/db mice in the metformin and LHZK groups were administered the corresponding drugs by gavage， while the blank control and model groups were given distilled water by gavage once daily for 8 consecutive weeks. Food intake， water consumption， body weight， and fasting blood glucose （FBG） were measured weekly. An automatic biochemical analyzer was used to determine glycated serum protein （GSP）， serum triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） staining was used to observe pathological morphological changes in the liver and pancreatic tissues. Oil red O staining was used to assess lipid accumulation in liver tissue. The anthrone colorimetric method was used to determine hepatic glycogen content. Real-time quantitative PCR （Real-time PCR） was used to detect the mRNA expression levels of insulin receptor substrate-1 （IRS-1）， Akt2， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6Pase） in liver tissue. Western blot was used to detect the protein expression of AMPKα， phosphorylated AMPKα （p-AMPKα）， GSK-3β， p-GSK-3β， glycogen synthase （GS）， and phosphorylated GS （p-GS） in liver tissue. ResultsCompared with the blank control group， the model group showed significantly increased food intake， water consumption， body weight， FBG， and GSP levels （P<0.01）. Pancreatic islets exhibited marked parenchymal cell hyperplasia and interstitial inflammatory cell infiltration. Liver tissue showed obvious steatosis， accompanied by a compensatory increase in hepatic glycogen content （P<0.01）. Hepatic G6Pase mRNA expression was increased， while IRS-1 and Akt2 mRNA expression levels were significantly decreased （P<0.01）. The p-AMPKα/AMPKα protein expression ratio showed a decreasing trend， whereas the p-GSK-3β/GSK-3β and p-GS/GS protein expression ratios were significantly increased （P<0.01）. Compared with the model group， food intake and water consumption showed decreasing trends in all treatment groups. Food intake was significantly reduced in the low- and high-dose LHZK groups and in the metformin group （P<0.05， P<0.01）， and water consumption was significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. No statistically significant differences in body weight were observed among the LHZK groups， whereas body weight in the metformin group was significantly increased （P<0.05， P<0.01）. FBG showed a decreasing trend in all treatment groups， with significant decreases in the low-dose LHZK group and the metformin group （P<0.05， P<0.01）. GSP levels were significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. Hepatic steatosis and pancreatic pathological injury were alleviated to varying degrees in all treatment groups. Hepatic glycogen content further increased in all treatment groups， with significant increases in the medium- and high-dose LHZK groups （P<0.05）. Real-time PCR results showed that all treatment groups downregulated the mRNA expression of G6Pase and PEPCK in the liver tissues of db/db mice， with significant downregulation of PEPCK mRNA in the low-dose LHZK and metformin groups （P<0.01）. Meanwhile， all treatment groups upregulated IRS-1 and Akt2 mRNA expression， with the most pronounced upregulation observed in the medium-dose LHZK group （P<0.01）. The p-AMPKα/AMPKα protein expression ratio was significantly increased in the low- and medium-dose LHZK groups （P<0.01）. The p-GSK-3β/GSK-3β protein expression ratio was significantly increased in all treatment groups （P<0.05， P<0.01）， whereas the p-GS/GS protein expression ratio was significantly decreased in all treatment groups （P<0.01）. ConclusionLHZK effectively reduces FBG and GSP levels in type 2 diabetic mice and improves hepatic steatosis and pancreatic islet pathological injury. Its hypoglycemic mechanism may be associated with regulation of the AMPK/Akt/GSK-3β signaling pathway and promotion of hepatic glycogen synthesis.

ObjectiveThis study aims to systematically review the marketed traditional Chinese patent medicines for treating chronic gastritis （CG） in China. By analyzing their variety characteristics and prescription patterns， it seeks to provide references for clinical syndrome differentiation-based drug selection， treatment method optimization， and the design of high-quality clinical research. MethodsInformation on marketed traditional Chinese patent medicines for treating CG was collected. Microsoft Excel software was used to collate and statistically analyze representative drugs for each pathological stage， market status， syndrome types， and other contents. The Ancient and Modern Medical Case Cloud Platform （V2.3.9） was employed to analyze the formula composition patterns of standardized prescriptions. ResultsA total of 141 marketed traditional Chinese patent medicines for treating CG in China were included. Based on the disease's pathological progression， they can be classified into drugs for non-atrophic gastritis， atrophic gastritis， and precancerous lesions. Post-marketing research reveals that relevant evaluation is only conducted on 17 drugs， of which 2 involve pharmacoeconomic studies and 14 possess standardized evidence-based evidence. The primary dosage forms were capsules， granules， and tablets. From the 100 prescriptions screened according to inclusion/exclusion criteria， the varieties indicated for the stomach collateral stasis syndrome in atrophic gastritis accounted for the highest proportion. The main efficacy distributions were clearing heat， detoxifying， and relieving pain by promoting Qi circulation. Core drugs included Glycyrrhizae Radix et Rhizome， Paeoniae Radix Alba， and Aucklandiae Radix. Medicinal properties were predominantly warm and neutral. Flavors were mainly bitter， pungent， and sweet. The drugs primarily entered the spleen and stomach meridians. Analysis of the package inserts reveals that 67 products list "contraindications"， 110 include "precautions"， and 23 explicitly state "adverse reactions". ConclusionTraditional Chinese patent medicines for treating CG hold unique value in clinical practice. However， currently there are challenges such as insufficient clarity in syndrome type descriptions within package inserts and a relative lack of high-level evidence-based medical evidence， as well as pharmacoeconomic evaluations. Future efforts should focus on addressing these shortcomings by advancing research on syndrome characteristics and medication patterns based on syndrome differentiation， systematically conducting pharmacoeconomic evaluations， strengthening the accumulation of high-level evidence-based evidence， and， on this basis， improving patient medication adherence. This will comprehensively enhance the clinical application value and scientific connotation of this category of drugs.

Objective: To explore the management of blood donors tested reactive to HCV in blood screening based on confirmation of HCV infection. Methods: Multiple HCV antibody assays, repeating HCV RNA testing, follow-up of blood donors and retesting of archive samples were performed to confirm HCV infection, identify infection status, and exclude false positives in blood donors reactive to HCV in blood screening. Results: From 2011 to 2024, the unqualified rate of HCV detection in blood screening was 2.45‰(2 751/1 122 026). Among these, anti-HCV+-&NAT-accounted for 1.85‰, followed by anti-HCV++ at 0.60‰. The proportion of anti-HCV+-&NAT-and HCV RNA yields was extremely low (0.007‰). The positive rate of anti-HCV+-&NAT-samples tested by electrochemiluminescence method (ELCIA) was approximately 7.5%, differing among reagents (P<0.05). The follow-up of anti-HCV+-&NAT-donors showed that 96.2% (202/210) were false positives, but 51.4% of donors remained anti-HCV+-&NAT-during follow-up. Among them, 8 donors (3.8%) could not be ruled out from HCV infection due to positive retesting by ELCIA. Of the anti-HCV+-&NAT-donors who were reactive at the first follow-up, 86.8% remained anti-HCV+-&NAT-at the second follow-up. The sampling confirmation data showed that all of 260 anti-HCV++ donors were confirmed as anti-HCV positive, and the proportion of false positives or missed detections by NAT was very low. Two occult HBV infections (OBIs) and one HBsAg carrier were identified among the 3 anti-HCV +-&NAT+ donors, and no HCV infection was confirmed in 5 anti-HCV--&HCV RNA + donors. Conclusion: The prevalence of HCV among blood donors in Dalian was about 0.06%, with extremely low proportion of window-period infection and slightly higher proportion of resolved infections than that of current infections. The majority of anti-HCV+-&NAT-were false positive. Blood donors confirmed as false positive should be qualified in blood screening 3 months later before next donation. In order to reduce the false positive results, it was advisable to avoid the same type of supplementary reagents as the initial reagents when performing confirmation.

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.

Background/Aims: Data from Asia regarding the short-term and long-term outcomes for acute severe ulcerative colitis (ASUC) are limited. We assessed the outcomes of ASUC, identified the risk factors for colectomy, and compared colectomy rates between the pre-biologics and post-biologics eras in Taiwan. Methods: The patients with an ASUC diagnosis between January 2013 and March 2022 at 5 tertiary medical centers were retrospectively analyzed. Results: In total, 98 patients were enrolled, with 68.4% diagnosed in the post-biologics era. In 78.6% of the ASUC patients initially received intravenous steroid therapy, for which the success rate was 74.1%. As for rescue therapy, 15 patients (93.8%) received biologics and 1 (6.3%) received cyclosporin. Biologics rescue therapy had a 93.3% success rate. One (1%) mortality due to septic shock occurred. The colectomy rate for index ASUC admission was 11.2%. Patients receiving colectomy were predominantly male (P= 0.012) and at older age (P= 0.016). Higher C-reactive protein (P= 0.035), lower albumin (P= 0.017), and hemoglobin (P= 0.023) levels were associated with colectomy risk. During a median follow-up of 24 months, 13 patients (15.1%) had recurrent ASUC and 23.1% of patients received colectomy. The accumulated colectomy rate at 3 years did not differ between the pre- and post-biologics eras (16.1% vs. 13.4%, P= 0.270). Conclusions This is the first Asian study on ASUC to compare colectomy rates between the prebiologics and post-biologics eras, revealing no significant difference. The recurrent ASUC had a higher colectomy rate than the index ASUC.

The compilation explanation for the Expert Consensus on Clinical Application of Ruyi Zhenbao pills systematically expounds the formulation methods and evidence-based basis of this consensus. In response to the weak clinical application evidence and ambiguous indications of Ruyi Zhenbao pills， the Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences， Wangjing Hospital of China Academy of Chinese Medical Sciences， and Dongzhimen Hospital of Beijing University of Chinese Medicine invited 39 experts from 31 medical institutions across China to complete the compilation through multi-disciplinary collaboration. The compilation strictly adheres to the World Health Organization （WHO） guidelines for guideline development and the GRADE evidence grading system. The work process covered the construction of clinical questions （a total of 30 clinical questions were determined based on expert voting results）， evidence retrieval （covering Chinese and English databases and gray literature）， safety assessment （integrating drug monitoring data and clinical research）， and the formation of recommendation opinions and consensus suggestions （18 recommendation opinions were reached through the GRADE grid method， and 22 consensus suggestions were reached through majority voting rules）. The results show that the consensus clearly states that this medicine is suitable for knee osteoarthritis， gouty arthritis， rheumatoid arthritis， neuropathic pain， and sequelae of stroke. In terms of safety， the adverse reactions are mainly gastrointestinal reactions such as nausea， vomiting， and abdominal pain. Pregnant women and those allergic to the ingredients of this medicine are contraindicated. The compilation process underwent three rounds of expert reviews and adopted methods such as nominal group technique and Delphi method to ensure the rigor of the consensus compilation process. It provides a paradigm for the formulation of expert consensus on clinical application of Tibetan medicine through the academic promotion and dynamic revision.

Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.

Objective:To investigate the dynamic changes of plasma high-mobility group box 1 (HMGB1) and its correlation with functional outcome and symptomatic intracranial hemorrhage (sICH) after endovascular treatment (EVT) in patients with acute large vessel occlusion stroke (ALVOS).Methods:Patients with ALVOS admitted to the Department of Neurology, Zengcheng District, Nanfang Hospital, Southern Medical University from June 2021 to April 2023 were included retrospectively. Plasma HMGB1 before EVT and at 6, 24, and 48 hours after procedure was detected, and the dynamic changes of plasma HMGB1 were compared and analyzed. The primary endpoint was the functional outcome evaluated using the modified Rankin Scale at 90 days of onset. A score of 0-2 was defined as good outcome and >2 was defined as poor outcome. The secondary endpoint was sICH, which was defined as the occurrence of hemorrhagic infarction after EVT and an increase of ≥4 in the National Institutes of Health Stroke Scale (NIHSS) score from baseline. Multivariate logistic regression analysis was used to evaluate the predictive value of HMGB1 for poor outcome and sICH. Results:A total of 73 patients with ALVOS received EVT were included. There were 54 males (74.0%), aged 62±12 years. The median time from onset to door was 90 minutes (interquartile range, 40-180 minutes), and the median time from onset to femoral artery puncture was 181 minutes (interquartile range, 140-280 minutes). Twenty-nine patients (39.7%) underwent bridging intravenous thrombolysis (IVT). At 90 days after onset, 37 patients (50.7%) had poor outcome, and 12 (16.4%) died during follow-up. Eleven patients (15.1%) developed sICH. After EVT, plasma HMGB1 showed a temporal increase, reaching its peak at 48 hours (median, 102.57 μg/L). Subgroup analysis showed that HMGB1 in the bridging IVT group at 6 hours ( P<0.05) and 24 hours ( P<0.05) after procedure were significantly higher than that at baseline. The non-bridging IVT group showed a significant increase at 6 hours after procedure ( P<0.05). There was no statistically significant difference in HMGB1 between the bridging IVT group and the non-bridging IVT group at the same time point. Multivariate logistic regression analysis showed that after adjusting for age, ischemic heart disease, triglycerides, uric acid, baseline NIHSS score, and sICH, the third quartile (adjusted odds ratio 7.087, 95% confidence interval 1.243-40.419; P=0.027) and fourth quartile (adjusted odds ratio 7.544, 95% confidence interval 1.260-45.172; P=0.027) of plasma HMGB1 were independent risk factors for poor outcome at 6 hours after procedure. The postoperative plasma HMGB1 in the sICH group was significantly higher than that in the non-sICH group ( P<0.05), but multivariate analysis showed no independent correlation between plasma HMGB1 and sICH. Conclusion:The elevation of plasma HMGB1 in patients with ALVOS at 6 hours after EVT is independently associated with poor outcome at 90 days after onset, but not with sICH.