OBJECTIVE: To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists. METHODS: By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements. RESULTS: The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development. CONCLUSION Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans ; China ; Surveys and Questionnaires ; Genetic Diseases, Inborn/genetics* ; Cross-Sectional Studies ; Genetics, Medical/education* ; Genetic Testing

ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury （CI/RI） in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase （PINK1/Parkin） signaling pathway-mediated mitophagy， and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups （n = 12 per group）： Sham-operated group， middle cerebral artery occlusion/reperfusion （MCAO/R） model group， low-， medium-， and high-dose modified Buyang Huanwu Tang groups （8.84， 17.68， 35.36 g·kg^-1·d^-1）， and an aspirin group （13.00 mg·kg^-1·d^-1）. Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin （HE） staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy （TEM）. Serum levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PINK1， Parkin， microtubule-associated protein 1 light chain 3B （LC3B， LC3Ⅱ/Ⅰ）， and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR （Real-time PCR） and Western blot， respectively. ResultsCompared with the sham-operated group， the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Severe cortical injury on the infarct side was observed， characterized by decreased neuronal density， cytoplasmic vacuolation， nuclear pyknosis， a marked reduction in Nissl bodies， dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons， and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly （P<0.01）. Mitochondria exhibited cristae membrane rupture and matrix vacuolation， with rupture of the outer mitochondrial membrane and formation of autophagosomes， the number of which increased significantly. Serum SOD activity decreased significantly （P<0.01）， while MDA content increased significantly （P<0.01）. In infarcted brain tissues of model mice， the relative mRNA expression and protein levels of PINK1， Parkin and LC3B were significantly increased （P<0.05， P<0.01）， whereas p62 mRNA and protein expression were significantly decreased （P<0.05， P<0.01）， showing statistical significance. Compared with the model group， all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Neuronal density increased significantly， cytoplasmic vacuolation was alleviated， nuclear morphology tended to be more regular and clearer， Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored， with some mitochondria showing autophagosome encapsulation， and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly （P<0.01）， while MDA content decreased significantly. The mRNA and protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ were significantly increased （P<0.05， P<0.01）， while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased （P<0.05， P<0.01）， showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ and downregulate p62 protein expression， suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.

Myocardial ischemia-reperfusion injury （MIRI） is a key complication of reperfusion therapy for ischemic heart disease. Due to its complex pathological mechanism， there is still a lack of targeted drugs and effective interventions in clinical practice. As the core organelle of cell energy metabolism， mitochondria not only undertake the key function of adenosine triphosphate （ATP） synthesis， but also maintain the homeostasis of intracellular environment by regulating ion dynamic balance， oxidative stress response and apoptosis. Mitophagy is an important mechanism to regulate mitochondrial homeostasis. Phosphatase and tensin homolog （PTEN）-induced putative kinase 1 （PINK1）/Parkin signaling pathway， as one of its core pathways， has been proved to have important physiological functions. Mitophagy mediated by PINK1/Parkin signaling pathway can synergistically act on the pathological process of MIRI through the multi-level regulatory mechanism of oxidative stress， calcium homeostasis imbalance and ferroptosis， so as to achieve the prevention and treatment of MIRI by reducing mitochondrial dysfunction and inhibiting programmed cell death. Studies have shown that modern drugs， such as proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors， DL-3-n-butylphenylpeptide， and dapagliflozin， active ingredients of traditional Chinese medicine such as phenols， saponins， flavonoids， and anthraquinones， as well as traditional Chinese medicine compounds and preparations such as Tongxinluo capsules， Shuangshen Ningxin capsules， and Qili Qiangxin capsules， can exert myocardial protection by regulating mitophagy mediated by this pathway and multiple targets. This study focuses on the PINK1/Parkin pathway， aiming to provide new ideas and directions for the prevention and treatment of MIRI from the perspective of PINK1/Parkin-mediated mitophagy.

ObjectiveTo observe the expression of miR-139/Notch1 axis and macrophage polarization in the homing changes of bone mesenchymal stem cells （BMSCs） in asthmatic rats， and to explore the possible mechanism of immune regulation by BMSCs during asthma. Methods30 male SD rats were randomly divided into three groups： normal control group， model control group and BMSCs implantation group， with 10 rats in each group. BMSCs labeled with CFSE were infused into the body of asthmatic rats through the tail vein， and the homing status of BMSCs in asthmatic lung tissue was detected by flow cytometry. Changes in the proportion of inflammatory cells in alveolar lavage fluid were detected by Wright-Giemsa Stain； the levels of macrophage polarization cytokines IFN⁃γ，IL-13，CD80 and CD206 in rat serum were detected by ELISA； the miR-139， Notch1， NOS2， Arg1 and CXCR4 in lung tissue were detected by RT-qPCR. ResultsCompared with the NC group， the expression of serum CD80 and IFN⁃γ in the MC group decreased， while the expression of IL-13 and CD206 increased （P<0.01）. The expression of miR⁃139 in lung tissue of MC group rats decreased， and the expression of macrophage polarization markers NOS2， Arg1， and homing marker CXCR4 genes increased （P<0.01）. Compared with the MC group， the expression of IFN-γ of rats in BMSCs group increased， while the expression of IL-13 and CD206 decreased （P<0.01）. The expression of miR⁃139， CXCR4， and SDF⁃1 mRNA in the lung tissue of rats of BMSCs group increased， while the expression of Notch1， NOS2， and Arg1 decreased （P<0.01）. Correlation analysis showed that CXCR4 was positively correlated with miR⁃139 （P<0.05）， while CXCR4 was negatively correlated with Notch1 （P<0.05）. SDF⁃1 and IFN⁃γ was a positively correlated （P<0.05）， while SDF⁃1 was negatively correlated with Arg1 and CD206 （P<0.05）. ConclusionThe miR⁃139/Notch1 axis can promote BMCs homing in asthmatic rats by affecting macrophage polarization in asthma.

Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction （GDFMD） in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome， thereby providing evidence-based medical evidence for the treatment of Wilson's disease （WD）-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1， 2023， to October 1， 2024. Participants were divided into a control group and an observation group， with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate （DMPS）. On this basis， the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days， for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses， respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement （LSM）， liver serological markers ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， type Ⅳ collagen （C-Ⅳ）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢNP）， and hyaluronic acid （HA）］， fibrosis index based on 4 factors （FIB-4）， AST to platelet ratio index （APRI）， unified Wilson's disease rating scale part Ⅱ （UWDRS-Ⅱ）， traditional Chinese medicine （TCM） syndrome score， 24-hour urinary copper， and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment， LSM levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses， and the improvement of LSM levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the levels of HA， LN， PⅢNP， and C-Ⅳ decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses， and the levels of HA， LN， and PⅢNP were more obvious （P<0.05）. After four treatment courses in the observation group， the levels of HA， LN， PⅢNP， and C-Ⅳ were improved more significantly （P<0.05）. Compared with those before treatment， ALT and AST levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with the control group after treatment， there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses， and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， APRI score and FIB-4 index level decreased in both groups after two and four treatment courses （P<0.05）. Compared with those in control group after treatment， there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses， and the APRI score in the observation group was more obvious after four treatment courses （P<0.05）， with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment， the levels of TCM syndrome scores decreased in both groups after two and four treatment courses （P<0.05）. Compared with that of the control group after treatment， there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses， and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously， and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses （P<0.05）. Compared with those of the control group after treatment， there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses， and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious （P<0.05）. Compared with those before treatment， the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses （P<0.05）. Compared with those in the control group after treatment， the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses （P<0.01）. After two treatment courses， the 24-h urine copper level in the observation group showed a gradual decreasing trend， although it was higher than that before treatment. After four treatment courses， the control group had an improvement rate of 91.43%， an effective rate of 34.29%， and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%， an effective rate of 71.43%， and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group （P<0.05）. Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy， and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety， which is worthy of clinical popularization and application.

AIM: To study the clinical characteristics and influencing factors of retinopathy of prematurity(ROP), and to construct a nomogram model for predicting ROP in premature infants.METHODS: This retrospective study enrolled premature infants who underwent fundus examinations in the hospital from January 2022 to September 2025 for analysis. Fundus examinations were performed using the RetCam III system, and the occurrence of ROP was recorded. The data were split into a training set and a validation set at a ratio of 7:3. Univariate analysis was conducted using the Chi-square test and multivariate analysis was performed using binary Logistic regression on the training set data. Variables identified in the multivariate analysis were used to construct a nomogram, which was subsequently validated.RESULTS: The incidence of ROP(428 cases)among the 3 841 premature infants was 11.43%, with 138 cases(32.24%)in stage I, 151 cases(35.28%)in stage II, 103 cases(24.07%)in stage III, 33 cases(7.71%)in stage IV, and 3 cases(0.70%)in stage V. No statistically significant differences were found in the clinical data between the training and validation sets(all P>0.05). Multivariate analysis identified neonatal sepsis, mechanical ventilation, transfusion therapy, coagulation dysfunction, bronchopulmonary dysplasia(BPD), neonatal respiratory distress syndrome(NRDS), formula feeding, and non-invasive respiratory support duration >1 wk as risk factors for ROP(all P<0.05). Birth weight(1 500-2 499 g, ≥2 500 g), gestational age(32-34 wk, 35-36 wk), weight gain rate ≥20 g/d, and 5-minute Apgar score ≥8 were identified as protective factors(all P<0.05). The area under curve(AUC)of the nomogram prediction model was 0.890 in the training set and 0.907 in the validation set, with sensitivity of 80.67% and 82.81%, and specificity of 83.18% and 85.14%, respectively. The calibration curves in both sets approached the ideal curve, and the Hosmer-Lemeshow goodness-of-fit test indicated good agreement between the predicted and observed values(χ2=12.918, P=0.115; χ2=4.047, P=0.853). The decision curve analysis demonstrated high net benefits in both the training and validation sets.CONCLUSION: The incidence of ROP in premature infants was 11.43%. The nomogram model, constructed based on multivariate Logistic regression and integrating key risk and protective factors such as birth weight, gestational age, sepsis, and mechanical ventilation, demonstrates high predictive value, good calibration, and high net benefit. It can serve as an intuitive and effective tool for early individualized risk assessment of ROP in premature infants.

Objective To improve the analysis method of the blood components of Yinchenhao decoction （YCHD） in vivo and explore its anti-hepatocellular carcinoma mechanism. Methods Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS） was used to collect and analyze blood samples from mice. The mice were given a single dose of YCHD with a concentration of 0.1 g/ml and a dose of 25 ml/kg, and then the samples were collected 2 h post–administration, which was to systematically study the chemical components of YCHD in vivo. Network pharmacological methods were used to screen the components and targets of YCHD, and the targets of hepatocellular carcinoma; The common targets of YCHD and hepatocellular carcinoma were identified for GO enrichment and KEGG enrichment. Molecular docking was performed on the main targets to verify the binding ability between the active ingredients and the core targets. The relative mRNA expression levels of serine/threonine-protein kinase（AKT1） and tumor protein p53（TP53） in liver tissues were analyzed via qPCR, including the following mouse groups: mice with concanavalin A（Con-A）-induced acute liver injury without preventive administration, mice with Con-A-induced acute liver injury that received 14 d preventive oral administration of YCHD, and untreated control mice. Results ①The active ingredients of YCHD in the blood were identified by retrieving the data from the in vitro component analysis. They were chrysophanol, herniarin, aloe-emodin, and monotropein. ②The mechanism of action of the blood components against hepatocellular carcinoma （HCC） was further analyzed using network pharmacological methods, and a total of 30 components of YCHD were screened for 213 targets and 215 HCC targets. ③There were 17 intersection targets between YCHD and hepatocellular carcinoma, including AKT1, TP53, receptor tyrosine-protein kinase erbB-2 （ERBB2）, myelocytomatosis oncogene （MYC）, interleukin-1β （IL-1β）, etc. The GO enrichment results indicated that these components were primarily involved in DNA replication，chromosome segregation，leukocyte mediated immunity，leukocyte cell-cell adhesion. The KEGG enrichment results demonstrated that these components were predominantly associated with diverse cancer pathways. Additionally, the results indicated involvement in the citrate cycle （TCA cycle）, pyruvate metabolism, and p53 signaling pathway, ect. ④The results of molecular docking showed that chrysophanol, herniarin, and aloe - emodin had strong binding abilities with AKT1, TP53, ERBB2, MYC, and IL-1β. ⑤The relative expression of AKT1 and TP53 mRNA was significantly higher in the modelling group than in the control group. The relative expression of AKT1 and TP53 mRNA was significantly lower in the drug administration group than in the modelling group. Conclusion There were 4 blood components in YCHD, among which chrysophanol, herniarin, and aloe-emodin may act on AKT1, TP53, ERBB2, MYC, IL-1β and then participated in the regulation of cancer signaling pathways and p53 signaling pathway to play a role in the treatment of HCC.

ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction （GDFMD） in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome， thereby providing evidence-based medical evidence for the treatment of Wilson's disease （WD）-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1， 2023， to October 1， 2024. Participants were divided into a control group and an observation group， with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate （DMPS）. On this basis， the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days， for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses， respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement （LSM）， liver serological markers ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， type Ⅳ collagen （C-Ⅳ）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢNP）， and hyaluronic acid （HA）］， fibrosis index based on 4 factors （FIB-4）， AST to platelet ratio index （APRI）， unified Wilson's disease rating scale part Ⅱ （UWDRS-Ⅱ）， traditional Chinese medicine （TCM） syndrome score， 24-hour urinary copper， and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment， LSM levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses， and the improvement of LSM levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the levels of HA， LN， PⅢNP， and C-Ⅳ decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses， and the levels of HA， LN， and PⅢNP were more obvious （P<0.05）. After four treatment courses in the observation group， the levels of HA， LN， PⅢNP， and C-Ⅳ were improved more significantly （P<0.05）. Compared with those before treatment， ALT and AST levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with the control group after treatment， there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses， and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， APRI score and FIB-4 index level decreased in both groups after two and four treatment courses （P<0.05）. Compared with those in control group after treatment， there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses， and the APRI score in the observation group was more obvious after four treatment courses （P<0.05）， with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment， the levels of TCM syndrome scores decreased in both groups after two and four treatment courses （P<0.05）. Compared with that of the control group after treatment， there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses， and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously， and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses （P<0.05）. Compared with those of the control group after treatment， there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses， and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious （P<0.05）. Compared with those before treatment， the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses （P<0.05）. Compared with those in the control group after treatment， the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses （P<0.01）. After two treatment courses， the 24-h urine copper level in the observation group showed a gradual decreasing trend， although it was higher than that before treatment. After four treatment courses， the control group had an improvement rate of 91.43%， an effective rate of 34.29%， and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%， an effective rate of 71.43%， and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group （P<0.05）. Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy， and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety， which is worthy of clinical popularization and application.