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.

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.

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.

ObjectiveTo screen and identify uridine diphosphate （UDP）-rhamnose synthase （RHM） genes from Ornithogalum saundersiae and verify their UDP-rhamnose （UDP-Rha） biosynthetic functions， thereby providing reliable candidate genes for the efficient biosynthesis of neohesperidin and other rhamnoside natural products. MethodsBased on previously reported plant RHM sequences， two candidate RHM genes， OsRHM1 and OsRHM2， were identified from O. saundersiae through transcriptome screening and sequence alignment. The two genes were cloned and subjected to bioinformatics analysis and multiple sequence alignment. An in vitro RHM-Cm1，2RhaT cascade reaction was established， and the ability of OsRHM1 and OsRHM2 to catalyze the conversion of UDP-glucose （UDP-Glc） to UDP-Rha was evaluated based on neohesperidin production. Real-time fluorescence quantitative polymerase chain reaction PCR （Real-time PCR） was performed to analyze the relative expression levels of the two genes in roots， bulbs， and leaves. ResultsThe open reading frame （ORF） of OsRHM1 was 2 076 bp and encoded 692 amino acids， with a predicted protein molecular mass of 77.97 kDa and a theoretical isoelectric point of 7.25. The ORF of OsRHM2 was 2 019 bp and encoded 673 amino acids， with a predicted protein molecular mass of 75.82 kDa and a theoretical isoelectric point of 7.24. Multiple sequence alignment showed that OsRHM1 and OsRHM2 contained the typical conserved motifs GxxGxxG/A and YxxxK of the plant RHM family and shared high amino acid sequence identity with previously reported RHMs. The in vitro cascade reaction demonstrated that both OsRHM1 and OsRHM2 were capable of catalyzing the conversion of UDP-Glc to UDP-Rha. The neohesperidin production in the OsRHM2 cascade reaction system was approximately 2.58-fold that in the OsRHM1 system. Real-time PCR analysis showed that the relative expression levels of OsRHM1 and OsRHM2 were higher in roots than in bulbs and leaves. ConclusionOsRHM2 exhibited a relatively high capacity for UDP-Rha supply and may serve as a candidate enzyme resource for the subsequent biosynthesis of rhamnoside natural products and the construction of UDP-Rha supply systems.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.

ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology（GO） enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software， and the protein-protein interaction （PPI） network for key targets was depicted. Finally， the hub gene was determined through topological analysis. Auto Dock， PyMOL， and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments， a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin（HE） staining， uric acid test， enzyme linked immunosorbent assay（ELISA）， Western blot， and real-time polymerase chain reaction（Real-time PCR）， the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values， 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response， astrocyte activation， regulation of interleukin （IL）-8 production， nuclear receptor activity， and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway， advanced glycosylation end/receptor of advanced glycation endproducts（AGE/RAGE） signaling pathway， anti-inflammatory， and other pathways. PPI network indicated that albumin（ALB）， peroxisome proliferator-activated receptor-γ （PPAR-γ）， IL-6， IL-1β， and C-reactive protein（CRP） were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene （β-carotene）. Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose （7.76 g·kg^-1·d^-1）， medium-dose （15.53 g·kg^-1·d^-1）， and high-dose （31.05 g·kg^-1·d^-1） groups of Buyang Huanwu Tongfeng decoction had different degrees of remission， and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration， as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced， followed by the medium-dose and low-dose groups， and the expression of ALB， PPAR-γ， IL-6， IL-1β， and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB， PPAR-γ， IL-6， IL-1β， and CRP， inhibiting the PPAR-γ/nuclear transcription factor （NF）-κB pathway， and reducing AGEs/RAGE-mediated inflammation， Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveThis study aims to enhance of the farnesyl pyrophosphate（FPP） pool in Saccharomyces cerevisiae by heterologously expressing different farnesyl diphosphate synthases（FPSs） from various plants， thereby increasing the production of terpenoid compounds by the engineered yeast. MethodsRNA from mixed samples of roots， stems， and leaves of seven plants including Arabidopsis thaliana， Rosa rugosa， Artemisia annua， Centella asiatica， Humulus lupulus， Medicago sativa， and Panax ginseng was extracted by column chromatography and reverse transcribed into the first strand of complementary DNA（cDNA）， and based on the transcriptome data of the seven species of plants， sequence-specific primers were designed for CaFPS， RrFPS， MsFPS， HiFPS， PgFPS， AtFPS， and AaFPS， the full-length of the genes was cloned， and the genes were analyzed for bioinformatics in order to construct a pESC yeast shuttle vector. These seven plant-derived FPSs were further heterologously expressed in the previous constructed β-elemene-producing yeast， and the yield of β-elemene was indicated for their catalytic acivities. ResultsThe coding sequences of CaFPS， RrFPS， MsFPS， HiFPS， PgFPS， AtFPS， and AaFPS were all of 1 021 bp in length and encoding 301 amino acids， all of which were similarly related to the endogenous FPS-encoding gene（ERG20） in S. cerevisiae. After heterologous expression， RrFPS was identified as the most effective in catalyzing the synthesis of FPP from isopentenyl pyrophosphate（IPP） and dimethylallyl pyrophosphate（DMAPP）. Compared to the control strains， the RrFPS overexpressed yeast strains YB-1-Rr and YB-3-Rr increased the production of β-elemene by 231.25% and 189.3%， respectively. ConclusionBy comparing the functions of FPS-encoding genes from seven different plant sources， it is determined that the protein encoded by the RrFPS from R. rugosa has the best catalytic ability， which can provide key genetic elements for the construction of engineered yeast strain constructs with high terpenoid production.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.