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

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

ObjectiveTo evaluate and analyze the syndrome characteristics of Qi and Yin deficiency accompanied by Qi stagnation and blood stasis in a rhein-induced cathartic colon （CC） rat model. MethodsTwenty-four rats were divided into a normal group and a model group （CC group）. The rats were administered equal volumes of physiological saline or 2% rhein suspension by gavage to establish the model over three cycles （approximately 118 days）. The first cycle lasted 46 days， with a dosage of 12 mL·kg^-1·d^-1， administered every other day. The second cycle lasted 37 days， with a dosage of 12 mL·kg^-1·d^-1， administered for 5 consecutive days followed by 2 days of cessation. The third cycle lasted 35 days， with a dosage of 16 mL·kg^-1·d^-1， also administered for 5 consecutive days followed by 2 days of cessation. Each cycle ended when 80% of the rats no longer exhibited loose stools. Body mass， 24 h food intake， coat condition， and coat red （R）， green （G）， and blue （B） values were recorded. The open field test （OFT） was used to measure the total distance traveled to evaluate Qi deficiency. The body mass coefficient and 24 h water intake were recorded to assess Yin deficiency. The sucrose preference test （SPT） was used to determine the sucrose preference rate （SPR）， and the average speed in OFT was measured to evaluate depressive status （liver depression and Qi stagnation）. Tongue images and their R， G， and B values were recorded. Whole blood viscosity （WBV） and plasma viscosity （PV） were measured using an automatic hemorheological analyzer to evaluate blood stasis. A carbon ink propulsion test was performed to determine the intestinal transit rate （ITR） for disease model evaluation. Hematoxylin-eosin （HE） staining was used to observe histopathological changes in the colon. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of transient receptor potential ankyrin 1 （TRPA1） and tryptophan hydroxylase 1 （TPH1） in colon tissue. Western blot was used to detect the protein expression of TRPA1 and TPH1. ResultsIn terms of syndrome indicators， compared with the normal group， the body mass of the CC group decreased （P<0.05）， while 24 h food intake increased （P<0.01）. The coats of the CC group appeared withered， disheveled， and dull， and the R， G， and B values of the coat decreased （P<0.01）. The total distance traveled in OFT decreased （P<0.01）. The body mass coefficient decreased （P<0.01）， while 24 h water intake increased （P<0.05， P<0.01）. The SPR decreased （P<0.01）， and the average speed in OFT slowed （P<0.01）. The tongue appeared dark red， and the R， G， and B values of tongue images decreased （P<0.01）. WBV and PV increased （P<0.01）. Regarding disease indicators， compared with the normal group， the ITR decreased in the CC group （P<0.01）. Pathologically， HE staining showed necrosis and shedding of colonic mucosal epithelial cells， disruption of mucosal continuity， and infiltration of inflammatory cells in the lamina propria in the CC group. Semi-quantitative analysis showed increased HAI scores （P<0.05） and increased inflammatory cell counts and area proportion （P<0.05）. In terms of molecular biological indicators， compared with the normal group， the mRNA and protein expression levels of TRPA1 and TPH1 in colon tissue decreased in the CC group （P<0.05， P<0.01）. ConclusionThe rhein-induced CC rat model conforms to the traditional Chinese medicine syndrome characteristics of Qi and Yin deficiency accompanied by Qi stagnation and blood stasis.

Objective To investigate the influencing factors of stroke patients with hypertension and their compliance with antihypertensive drugs, and to provide targeted intervention measures for stroke prevention in hypertensive patients.  Methods Using the method of multi-stage cluster sampling, a total of 59,434 permanent residents aged 40 and above were selected from 48 monitoring sites in 9 cities of Hebei Province from December 2019 to December 2020. Unconditional logistic regression analysis was used to explore the influencing factors of stroke complicated with hypertension and the compliance of patients with antihypertensive drugs.  Results Among the 59 434 subjects, the prevalence rate of stroke was 4.33% and the prevalence rate of stroke complicated with hypertension was 82.47%. The results of univariate analysis showed that the proportion of women, rural areas, dyslipidemia, diabetes, obesity, and people with family history of stroke was higher in stroke patients with hypertension, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that rural areas, dyslipidemia, diabetes, obesity, and family history of stroke significantly increased the risk of stroke, and the OR (95%CI) values were 1.29 (1.03-1.62), 1.39 (1.12-1.72), 1.58 (1.25-1.99), 1.61 (1.22-2.12) and 1.60 (1.26-2.04), respectively. Among stroke patients with hypertension, 92.71% of patients took antihypertensive drugs. It was found that women's compliance with antihypertensive drugs was good, with an OR (95%CI) value of 1.46 (1.01-2.09).  Conclusion The prevalence rate of stroke complicated with hypertension is high in people aged 40 and above in Hebei Province. Hypertensive people should lower blood lipids, control blood glucose, and lose weight as soon as possible to prevent the occurrence of stroke.

According to traditional Chinese medicine （TCM） theory， impaired spleen transportation function disrupts nutrient distribution， causing metabolic accumulation of lipids that transform into pathogenic phlegm-dampness. These pathological factors disseminate through the San Jiao and obstruct meridian pathways， ultimately forming the pathogenesis described as "all disorders involve phlegm". Phlegm and dampness share common pathogenic origins but manifest distinct clinical manifestations. Dampness， as the precursor， may congeal into phlegm， while existing phlegm accumulation can further exacerbate dampness stagnation， thereby establishing a self-perpetuating pathological cycle. Modern medical research has confirmed that the essence of "phlegm-dampness" syndrome is closely associated with energy metabolism disorders， serving as a common pathological basis for metabolic syndrome， type 2 diabetes mellitus， atherosclerosis， and other major chronic diseases. As a crucial vehicle for medical experimental research， disease-syndrome combination animal models serve as an indispensable means to advance the modernization of TCM. Currently， based on classical theories such as "rich and greasy foods produce phlegm" and "physical coldness combined with cold consumption causes external pathogens to invade the skin and hair， thereby generating internal dampness"， researchers primarily employ two paradigms to construct animal models of phlegm-turbidity， dampness obstruction， and phlegm-dampness syndromes： the first involves simulating TCM etiological factors （through methods like dietary irregularities， imblanace between work and rest， and combined internal-external dampness exposure）， while the second combines disease with syndrome differentiation （inducing pathological changes through physical， chemical， or biological interventions）. Through comprehensive evaluation incorporating macroscopic observation and microscopic index detection， model animals undergo systematic biological and pathological assessment， with further syndrome type verification achieved via the "prescription-based syndrome detection" approach. However， existing models still exhibit significant deficiencies in both the standardization of modeling methodologies and the systematization of evaluation criteria. This paper reviews the strategies for constructing "phlegm-dampness" syndrome animal models and their corresponding evaluation indices， focusing on the pathological correlations among different modeling approaches. The aim is to provide methodological guidance for research on TCM syndromes related to "phlegm-dampness" syndrome and to support the development of TCM therapies for resolving phlegm and eliminating dampness. This study not only contributes to advancing the standardization of TCM syndrome research but also provides crucial technical support for the modernization of TCM.

ObjectiveThis paper aims to investigate the differential mechanisms underlying the staged therapeutic effects of Qijia Rougan formula on liver fibrosis using proteomic technology. MethodsThe staged rat model of liver fibrosis was established by subcutaneous injection of carbon tetrachloride （CCl₄） and olive oil. One hundred and four SD rats were randomized into thirteen groups：a normal group，a two-week model group，a four-week model group，a six-week model group，an eight-week model group，a two-week Qijia Rougan formula group，a four-week Qijia Rougan formula group，a six-week Qijia Rougan formula group，an eight-week Qijia Rougan formula group，a two-week compound Biejia Ruangan tablet group，a four-week Compound Biejia Ruangan Tablet group，a six-week Compound Biejia Ruangan Tablet group，and an eight-week compound Biejia Ruangan tablet group. After two weeks of drug intervention，liver tissue and abdominal aortic blood samples were collected from the rats for testing. Hematoxylin-eosin （HE） staining，Masson staining，and Picro Sirius red staining were used to observe pathological damage and collagen fiber deposition in liver tissues. Immunohistochemistry （IHC） was employed to detect the contents of fibrosis markers in liver tissues. The contents of liver function indicators in the serum were measured using a fully automated biochemical analyzer，and the levels of liver fibrosis indicators in the serum were assessed by enzyme-linked immunosorbent assay （ELISA）. Liver tissues from the normal group，each model group，and each Qijia Rougan formula group were subjected to label-free quantitative proteomic analysis to identify differential proteins among the groups，with key proteins validated by Western blot. Finally，bioinformatics analysis was performed on the differential proteins. Results（1） The staged rat model of liver fibrosis constructed with CCl₄ and olive oil showed pathological results at the 2^nd，4^th，6^th，and 8^th weeks of modeling that were consistent with the Metavir standards for the F1，F2，F3，and F4 stages. Compared with those in the normal control group，the protein expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were significantly increased in each stage （P<0.05）. The levels of liver function indicators in the serum，including alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），direct bilirubin （DBIL），and total bilirubin （TBil） in each model group，were significantly elevated in each stage （P<0.01）. The levels of liver fibrosis indicators in the serum，including procollagen Ⅲ peptide （PⅢP），type Ⅳ collagen（Ⅳ-C），hyaluronic acid （HA），and laminin （LN） in each model group，were significantly increased in each stage （P<0.05，P<0.01）. This study successfully established a staged rat model of liver fibrosis. （2） Compared with the model groups at each stage，the administration groups showed a reduction in hepatocyte ballooning degeneration，a more orderly arrangement of hepatocytes，and a decrease of inflammatory cell infiltration. The blue-stained collagen fibers became significantly thinner and finer，with reduced and narrowed fibrous septa. The areas of collagen fibers and Picro Sirius red staining were reduced （P<0.05）. The positive areas of α-SMA and Collagen Ⅰ expression were significantly decreased （P<0.05）. The levels of ALT，AST，ALP，DBIL，and TBil in the rats of the model groups at each stage were significantly reduced （P<0.05，P<0.01）. The levels of PⅢP，Ⅳ-C，HA，and LN in the rats of the model groups at each stage were significantly decreased （P<0.05）. Among these，the improvements in all indicators were most significant in the F3 stage （P<0.01）.（3） The proteomic results show that a total of 165 differential proteins exhibit a callback trend when comparing the model groups at four stages with the normal group，and when comparing the Qijia Rougan formula group with the model group. Western blot analysis reveals that the levels of NAD（P）H：quinone oxidoreductase 1 （NQO1），mitogen-activated protein kinase 1 （MAPK1），arginase 1 （Arg1），and glutathione S-transferase α1 （GSTA1） were consistent with the proteomic results. Bioinformatics results reveal that 165 differentially expressed proteins are enriched in multiple signaling pathways. Notably，signaling pathways such as drug metabolism-cytochrome P450，arginine biosynthesis，and the peroxisome proliferator-activated receptor （PPAR） signaling pathway were found to be closely associated with liver fibrosis，suggesting that the Qijia Rougan formula may exert its staged regulatory effects on liver fibrosis by regulating these pathways. ConclusionThe Qijia Rougan formula may achieve staged regulation of liver fibrosis by regulating drug metabolism-cytochrome P450，arginine biosynthesis，and the PPAR signaling pathway.

Objective To analyze the prevalence of hyperuricemia (HUA) among adults in Hebei Province and its influencing factors related to comorbidities with ^“three highs^”, and to provide a theoretical basis for the prevention and control of HUA and multi-disease co-management. Methods Data were derived from the 2018 China Chronic Disease and Risk Factors Surveillance program conducted in Hebei Province. A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥18 years. All statistical analyses were adjusted for complex weighting. Design-based logistic regression was employed to analyze factors influencing HUA prevalence, and ordinal logistic regression was used to analyze the influencing factors of HUA patients and their comorbidity with ^“three highs^”. Results The prevalence of HUA among adults in Hebei Province was 10.42%, with males showing higher rates than females (P<0.05). The highest prevalence of HUA was observed in the 18-39 age group, followed by a declining trend, and a resurgence in those aged ≥70 (P<0.05). Among HUA patients with comorbidities, isolated HUA, 1 comorbidity, 2 comorbidities, and 3 comorbidities accounted for 13.94%, 33.33%, 39.17%, and 13.56%, respectively. HUA combined with hypertension and dyslipidemia represented the highest proportion (31.07%). Analysis of the influencing factors of HUA revealed that higher education levels, obesity, central obesity, and dyslipidemia increased the risk of HUA (P<0.05). Ordinal logistic regression analysis of HUA combined with three highs showed that HUA patients aged ≥50 years, overweight individuals, and those with chronic kidney disease had a higher number of patients with three highs (P<0.05). Conclusion HUA exhibits insidious onset, and it is recommended to include uric acid testing in routine physical examinations. Targeted prevention measures, such as early uric acid testing and health education, should be implemented by Hebei authorities for populations with higher education levels, obesity, central obesity, and dyslipidemia to reduce HUA incidence. Additionally, health education and regular medical check-ups are recommended for overweight HUA patients and those with chronic kidney disease to prevent comorbidities and alleviate disease burden.

Digital medical insurance governance， as an important component of digital transformation， improves the efficiency of medical insurance services while facing complex ethical challenges. Taking stakeholder theory as the analytical framework， this paper explored the generative mechanisms， manifestations， and countermeasures of ethical issues in digital medical insurance governance. This study uncovered that accelerated technological iteration and lagging ethical and legal norms， as well as interest conflicts among multiple participants in governance， constituted the major causes of ethical issues. These issues specifically manifested as data privacy leakage， unfair algorithmic decision-making， widening digital divide， ambiguous accountability， and other aspects. To address these issues， this paper put forward systematic countermeasures， such as establishing a dynamic ethical and legal regulatory system， balancing the demands of stakeholders， strengthening technological ethical governance， narrowing the digital divide， and enhancing accountability mechanisms. Through the implementation of multi-dimensional governance strategies， it aimed to balance technological innovation and ethical constraints， advance the inclusiveness， fairness， and sustainable development of digital medical insurance， and provide theoretical reference and practical references for improving China’s digital medical insurance governance system.

Mosquito-borne diseases pose a major threat to global public health. The gut microbiota colonizing the mosquito intestinal tract plays a critical role in regulating pathogen infection, replication, and transmission. This review summarizes the effects of mosquito gut microbiota on the transmission potential of mosquito-borne pathogens, explores the interaction mechanisms between gut microbial communities and pathogens, and discusses the potential of microbiome-based strategies to reduce mosquito-borne disease transmission.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.