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.

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.

Wilson disease （WD） is an autosomal recessive disorder of copper metabolism， and decoppering therapy and symptomatic treatment are the main Western medicine therapies for WD. This article systematically reviews the understanding of the etiology and pathogenesis of WD in traditional Chinese medicine （TCM） and points out that abnormal natural endowment is the core etiology and pathogenesis of WD， with internal accumulation of copper toxicity as the manifestation， liver/spleen/kidney dysfunction as the root cause， and intermingled “toxin， stasis， phlegm， and deficiency” as the key pathogenesis. Literature research and clinical observation are conducted to summarize the common TCM syndromes of WD， including stagnation of liver Qi， internal retention of damp-heat， phlegm-stasis-heat accumulation syndrome， liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency， and syndrome of deficiency damage and phlegm stasis. This article proposes the corresponding therapies and representative prescriptions for each syndrome and discusses the advantages of treatment by stage and integrated traditional Chinese and Western medicine therapy. This article aims to provide a systematic reference for the syndrome differentiation-based treatment of WD in clinical practice of TCM， thereby giving full play to the advantages of TCM in the treatment of this disease.

ObjectiveTo introduce the three main techniques for tuberculosis screening currently used in China, to systematically evaluate their accuracy in diagnosing latent tuberculosis infection (LTBI), so as to provide scientific basis and recommendations for the formulation of China’s tuberculosis screening strategy. MethodsLiterature on the diagnosis of tuberculosis by tuberculin skin test (TST), interferon-γ release assay (IGRA), and recombinant Mycobacterium tuberculosis fusion protein (EC) skin test from January 1, 2010 to August 22, 2024 was comprehensively retrieved from PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Database through computerized search. Besides, all the literature was screened in accordance to the inclusion criteria for diagnostic tests, and characteristic information of the literature selected was extracted simultaneously. Meta-analysis was performed using Stata 17.0 software, with a random-effects model used for weighted quantitative synthesis of included literature, calculating pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and their 95% confidence intervals (CI). ResultsA total of 543 relevant articles were retrieved, with 105 ultimately included. Among them, 33 articles reported diagnostic data for TST, with a pooled sensitivity of 0.68 (95%CI: 0.62‒0.73), specificity of 0.67 (95%CI: 0.60‒0.73), positive likelihood ratio of 2.0 (95%CI: 1.7‒2.5), and negative likelihood ratio of 0.48 (95%CI: 0.40‒0.58). Ninety-four articles reported the diagnostic value of IGRAs test, with a pooled sensitivity of 0.88 (95%CI: 0.87‒0.89), specificity of 0.82 (95%CI: 0.79‒0.84), positive likelihood ratio of 4.8 (95%CI: 4.2‒5.6), and negative likelihood ratio of 0.15 (95%CI: 0.13‒0.17). Data on EC skin test was limited, but preliminary analysis showed that it had high sensitivity and specificity. ConclusionIGRA has a significant advantage in diagnosing LTBI, and EC skin test also shows good diagnostic performance, although relevant data is limited. TST remains suitable for large-scale screening due to its cost-effectiveness.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

Objective To explore the effects of behavior change intervention based on the multi-ple-theory model on patients with dyslipidemic ischemic stroke.Methods A total of 93 patients with dyslipidemic ischemic stroke who were hospitalized in the vascular neurology ward of Beijing Tiantan Hospital,Capital Medical University from January to August 2024 were selected as the study subjects using the convenience sampling method.They were randomly divided into control group(n=49)and intervention group(n=44)using the envelope-drawing method.Patients in the control group re-ceived routine stroke health education,while those in the intervention group underwent a 3-month be-havior change program guided by the multiple-theory model.The levels of healthy behaviors,body mass index(BMI),total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDL-C),and low-density lipoprotein(LDL-C)were compared between the two groups.Results There were no statistically significant differences in general information and disease-related data between the two groups(P＞0.05).At 1-,3-,and 6-month after the intervention,the level of healthy behaviors in the intervention group was higher than that in the control group,with statistically significant differ-ences(P＜0.05).There was a statistically significant difference in BMI between the two groups at 6 months after the intervention(P＜0.05).The TC levels in the intervention group at 3 and 6 months after the intervention were lower than those in the control group,with statistically significant differences(P＜0.05).The HDL-C level in the intervention group at 6 months after the intervention was high-er than that in the control group,with a statistically significant difference(P＜0.05).The LDL-C levels in the intervention group at 1-,3-,and 6-month after the intervention were lower than those in the control group,with statistically significant differences(P＜0.05).There were no statistically significant differences in TG levels between the intervention group and the control group at different time points after the intervention(P＞0.05).Conclusion The behavior change intervention pro-gram based on the multiple-theory model can effectively improve and maintain healthy behaviors and improve blood lipid levels in patients with dyslipidemic ischemic stroke.

OBJECTIVE To investigate the mechanism of baicalin in alleviating the intestinal mucosal barrier injury in rats with intraperitoneal infection-induced sepsis through the vitamin D receptor(VDR)/nuclear factor E2-relat-ed factor 2(Nrf2)/haemoglobin oxygenase-1(HO-1)signalling pathway.METHODS Twenty-four SD rats were randomly divided into a sham-surgery group,a model group,an ulinastatin group and a baicalin group,with six rats in each group.Sepsis models were established via cecal ligation and puncture(CLP)in rats in each groups ex-cept for the sham surgery group.Six hours after modeling,the sham-surgery and the model groups received intra-peritoneal saline,while the ulinastatin and baicalin groups were administered ulinastatin at 20,000 U/kg and ba-icalin at 100 mg/kg,respectively,via intraperitoneal injection once daily for 5 consecutive days.The histopatho-logical changes in the ileum tissue of rats in each group were observed,and the levels of oxidative stress,inflam-matory factors,and the expression of related mRNA and proteins in the VDR/Nrf2/HO-1 signalling pathway were compared.RESULTS Compared with the sham-surgery group,the model group showed disordered villus ar-rangement,severe intestinal mucosal atrophy and inflammatory cell infiltration,with necrotic epithelial cell shed-ding.Additionally,in the model group,the total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and glutathione peroxidase(GSH-PX)levels reduced,while the levels of tumor necrosis factor-α(TNF-α),inter-leukin(IL)-6,and IL-1βsignificantly increased,and the expression of VDR mRNA,Nrf2 mRNA,HO-1 mR-NA,and VDR,Nrf2,and HO-1 proteins were downregulated(P<0.05).Compared with the model group,the ulinastatin group and the baicalin group showed that villus arrangement,intestinal mucosal atrophy and inflamma-tory cell infiltration got improved,the levels of T-AOC,SOD,and GSH-PX elevated,the levels of TNF-α,IL-6,and IL-1βdecreased,and expressions of VDR mRNA,Nrf2 mRNA,HO-1 mRNA,and VDR,Nrf2,and HO-1 proteins were upregulated.Moreover,all indicators in the baicalin group were superior to those in the ulinastatin group(P<0.05).CONCLUSION Baicalin can inhibit the expression of inflammatory factors and regulate the bal-ance of oxidative stress in vivo by up-regulating the VDR/Nrf2/HO-1 signaling pathway,thereby alleviate the in-testinal mucosal barrier dysfunction caused by intraperitoneal infection-induced sepsis.

Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.

Objective:To explore the mechanism of TLR4/ERK1/2 signaling pathway in progesterone regulating expression of IL-8 in decidual stromal cells(DSCs).Methods:Human DSCs on early pregnancy were isolated and cultured in vitro.The cells were treated with 0.01 μmol/L,0.1 μmol/L and 1 μmol/L progesterone,respectively.Expressions of IL-8,TLR4,ERK1/2 and p-ERK1/2 were detected by Western blot.TLR4 inhibitor TAK-242 and ERK1/2 inhibitor U0126 were further treated,and expression of IL-8 in progesteron+inhibitor group,progesterone group and control group was detected by Western blot.Results:With the increase of pro-gesterone concentration,expression of IL-8 in DSCs decreased gradually.Expressions of DSCs IL-8,TLR4 and p-ERK1/2 in 0.01 μmol/L progesterone group were lower than those in control group(P=0.035 8,P=0.019 4 and P=0.047 1).Expressions of IL-8,TLR4 and p-ERK1/2 in DSCs in 0.1 μmol/L progesterone group were significantly lower than those in control group(P=0.003 5,P=0.004 0 and P=0.009 9).Expressions of IL-8,TLR4 and p-ERK1/2 in DSCs in 1 μmol/L progesterone group were significantly lower than those in control group(P=0.003 3,P=0.001 6 and P=0.005 0).Expression of IL-8 in progesterone+TAK-242 group was signifi-cantly lower than that in progesterone group(P=0.009 1),and expression of IL-8 in progesterone+U0126 group was significantly lower than that in progesterone group(P=0.004).Conclusion:TLR4/ERK1/2 signaling pathway is involved in the physiological process of progesterone regulating expression of IL-8 in DSCs,and progesterone reduces IL-8 expression by inhibiting expression of TLR4 and phosphorylation activation of ERK1/2.