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.

Objective:To investigate effect of SenkyunolideⅠ(Sen Ⅰ)on function of astrocytes induced by lipopolysaccharide(LPS)and its mechanism.Methods:Rat neural astrocytes were induced by LPS,and the damaged cell model was constructed.Normal and injured astrocytes were treated with different concentrations of Sen Ⅰ(20,50,100,200 μmol/L),respectively.Cell proliferation was detected by CCK-8,cytotoxicity was detected,and the optimal concentration of Sen Ⅰ was determined.Astrocytes were divided into control group,LPS group,LPS+Sen Ⅰ group and LPS+Sen Ⅰ+ML385[nuclear factor E2 associated factor 2(Nrf2)inhibitor]group.Cell proliferation was detected by CCK-8 assay,expression of glial fibrillary acidic protein(GFAP)was detected by immunofluorescence assay and Western blot,mRNA and protein expression of Nrf2 was detected by qRT-PCR and Western blot,contents of TNF-α and IL-1β in supernatant of cells were detected by ELISA,and expression of glial cell line-derived neurotrophic factor(GDNF)in cells was detected by Western blot.Results:Low concentrations of Sen Ⅰ(20,50 μmol/L)were not toxic to astrocytes,while high concentra-tions(100,200 μmol/L)significantly inhibit astrocyte proliferation.The optimal concentration of Sen Ⅰ was 50 μmol/L.Compared with control group,cell proliferation ability,contents of TNF-α and IL-1β in cell supernatant,and expression of GFAP in cells were significantly increased in LPS group(P<0.01),while Nrf2 mRNA and protein level and GDNF protein level in cells were significantly decreased(P<0.01);compared with LPS group,cell proliferation ability,contents of TNF-α and IL-1β in cell supernatant,and ex-pression of GFAP in LPS+Sen Ⅰ group were significantly decreased(P<0.05),while Nrf2 mRNA and protein level and GDNF protein level in cells were significantly increased(P<0.05);compared with LPS+Sen Ⅰ group,LPS+Sen Ⅰ+ML385 group could reverse the above effects(P<0.05).Conclusion:Sen Ⅰ can inhibit the over-activation and inflammatory injury of astrocytes,and the mechanism may be related to the activation of Nrf2 pathway.

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.

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.

Objective:To investigate effect of SenkyunolideⅠ(Sen Ⅰ)on function of astrocytes induced by lipopolysaccharide(LPS)and its mechanism.Methods:Rat neural astrocytes were induced by LPS,and the damaged cell model was constructed.Normal and injured astrocytes were treated with different concentrations of Sen Ⅰ(20,50,100,200 μmol/L),respectively.Cell proliferation was detected by CCK-8,cytotoxicity was detected,and the optimal concentration of Sen Ⅰ was determined.Astrocytes were divided into control group,LPS group,LPS+Sen Ⅰ group and LPS+Sen Ⅰ+ML385[nuclear factor E2 associated factor 2(Nrf2)inhibitor]group.Cell proliferation was detected by CCK-8 assay,expression of glial fibrillary acidic protein(GFAP)was detected by immunofluorescence assay and Western blot,mRNA and protein expression of Nrf2 was detected by qRT-PCR and Western blot,contents of TNF-α and IL-1β in supernatant of cells were detected by ELISA,and expression of glial cell line-derived neurotrophic factor(GDNF)in cells was detected by Western blot.Results:Low concentrations of Sen Ⅰ(20,50 μmol/L)were not toxic to astrocytes,while high concentra-tions(100,200 μmol/L)significantly inhibit astrocyte proliferation.The optimal concentration of Sen Ⅰ was 50 μmol/L.Compared with control group,cell proliferation ability,contents of TNF-α and IL-1β in cell supernatant,and expression of GFAP in cells were significantly increased in LPS group(P<0.01),while Nrf2 mRNA and protein level and GDNF protein level in cells were significantly decreased(P<0.01);compared with LPS group,cell proliferation ability,contents of TNF-α and IL-1β in cell supernatant,and ex-pression of GFAP in LPS+Sen Ⅰ group were significantly decreased(P<0.05),while Nrf2 mRNA and protein level and GDNF protein level in cells were significantly increased(P<0.05);compared with LPS+Sen Ⅰ group,LPS+Sen Ⅰ+ML385 group could reverse the above effects(P<0.05).Conclusion:Sen Ⅰ can inhibit the over-activation and inflammatory injury of astrocytes,and the mechanism may be related to the activation of Nrf2 pathway.

Objective:Analyze the epidemiological data and the clinical data of local foodborne botulism, summarize the influencing factors and clinical characteristics of the foodborne botulism, mitigate future misdiagnosis.Methods:An epidemiological investigation was conducted to a local outbreak with botulism, which involved 24 individuals consuming homemade bean curd and 14 cases with foodborne botulism through analyzing the influencing factors of the poisoning. For 14 patients with botulism, their clinical manifestations, first laboratory test and imaging data, treatment and prognosis, were documented and explored.Results:All 14 cases were diagnosed as type A foodborne botulism, of which 2 were misdiagnosed. The incidence of the foodborne botulism was reduced by 81.7% in alcoholic drinkers ( P=0.009). The median incubation period of the 14 patients with botulism was 2.0 (1.0~3.0) days. The initial clinical symptom of 10 patients was diplopia, while that of the other 4 patients was blurred vision. Nine patients subsequently suffered from paralysis of oropharyngeal muscles, leading to dysphagia, speech impairment, etc. Four patients progressed to dyspnea and chest tightness due to respiratory muscle involvement. All of the patients had clear consciousness without sensory abnormalities, no fever and abdominal symptoms such as diarrhea and abdominal pain. There were no obvious abnormal findings in 14 patients with laboratory tests and cranial CT/MRI assessment. 14 patients with the poisoning were relieved after injection of botulinum antitoxin for 8.0 (7.0~8.5) days. Follow-up of all the patients 6 months later found that 9 patients still had slight blurred vision. Conclusions:The typical clinical manifestation of foodborne botulism was symmetric descending flaccid paralysis. Drinking liquor could reduce the incidence of foodborne botulism. Botulinum antitoxin was effective in the treatment of botulism and should be used as early as possible.

Objective: To investigate the expression of macrophage migration inhibitory factor (MIF) in pulmonary tissues from patients with chronic obstructive pulmonary disease (COPD) and the relationship with its clinical features. Methods: One hundred and eighty patients who underwent pulmonary bullectomy lobectomy due to pneumatocele from January 2015 to September 2018 in Longgang Central Hospital were enrolled and classified into patients without COPD (control group)and patients with COPD (COPD group), with 90 patients each group. According to the lung function parameters, 90 patients with COPD were divided into the mild COPD group, the moderate COPD group, and the severe COPD group. The levels of mRNA and protein of MIF were measured with RT-PCR, ELISA and Western blot. One-way ANOVA, Pearson correlation analysis and SNK-q test were used to analyze the results with SPSS 18.0, and P<0.05 was considered statistically significant. Results: The level of MIF in pulmonary tissues from the control group was obviously lower than those in the COPD group (P<0.05). The level of MIF in pulmonary tissues in the severe COPD group was obviously higher than those in pulmonary tissues in the mild COPD, moderate COPD and control groups (P<0.05). MIF was positively correlated with the lung function parameters (P<0.05). Conclusion The high expression of MIF in pulmonary tissues is closely related to the severity of COPD.

Objective To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in patients with traumatic brain injury (TBI) and their clinical significance. Methods Peripheral blood and brain tissue samples were obtained from 60 TBI patients. According to the GCS score, 60 TBI patients were divided into the moderate damage group, the severe damage group and the especially severe damage group. According to the different time points after the injury, the patients were divided into <6 hours group, 6-24 hours group, 24-72 hours group and >72 hours group. The 60 control brain tissue samples were obtained from patients with cerebral aneurysms and undergoing craniotomy at the same time; and control peripheral blood were collected from 60 healthy people. The levels of HIF-1α were measured with RT-PCR and Western blot . One-way ANOVA and t-test were used to analyze the results with SPSS 18.0. Results The expression of HIF-1α in the control group [peripheral blood: HIF-1α mRNA (0.35±0.12), HIF-1α protein (0.28±0.06) ;brain tissue: HIF-1α mRNA (0.65±0.08),HIF-1α protein (0.78±0.08)] was obviously lower than those in the TBI groups, and the differences were statistically significant (P<0.05). Along with the damage degree aggravating, the expression of HIF-1α was increased. The expression of HIF-1α in the especially severe damage group was statistically higher than those of the severe damage group and the moderate damage group (P<0.05). The expression of HIF-1α was increased along with the extension of time after the injury. The expression of HIF-1α in the 24-72 h group was significantly higher than those of the >72 h group, 6-24 h group and <6 h group (P<0.05). Conclusions The expression of HIF-1α is closely related to the severity of TBI and may play an important role in the progress of TBI.

Objective To establish a numerical model of the shear module of alginate beads stimulated by ultrasonic sound.Methods The compression ratio and force of alginate beads were recorded with the compression test .The shear module of beads was measured with a Hertz model .When to alginate beads were stimulated ultrasonically for different durations , the ultrasonic stimulation power , ultrasonic pulse ratio , and changes in the shear module and solution temperature were measured.Results Temperatures in the solution and shear module of alginate beads increased under different ultrasonic stimulation conditions .Modeling analysis revealed the relationship between the shear module of alginate beads and the corresponding temperature .The shear module of beads was in a quadratic equation with temperature (20℃