ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling （GDL） exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups： the normal group， the model group， the GDL low-， medium-， and high-dose groups （0.24， 0.48， 0.96 g·kg^-1）， and the penicillamine group （90 mg·kg^-1）， with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg^-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of hyaluronic acid （HA）， laminin （LN）， procollagen type-Ⅲ peptide （PC-Ⅲ）， and collagen type-Ⅳ （C-Ⅳ）. Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 （LncRNA H19）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR）. Western blot analysis was performed to assess the expression levels of PI3K， Akt， mTOR， and their phosphorylated forms， as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B （LC3-Ⅱ/LC3-Ⅰ） in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group， the model group exhibited inflammatory cell infiltration in hepatocytes， unclear nuclear boundaries with cell cleavage and necrosis， and collagen fiber deposition around confluent areas. The levels of HA， LN， PC-Ⅲ， and C-Ⅳ were significantly elevated （P<0.01）. Transmission electron microscopy revealed an increased number of autophagic vesicles， with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased （P<0.01）， and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were reduced （P<0.01）， while LncRNA H19 expression was increased （P<0.01）， and mRNA expression levels of PI3K， Akt， and mTOR were decreased （P<0.01）. After treatment with GDL， the degree of liver fibrosis was significantly improved， with decreased levels of HA， LN， PC-Ⅲ， and C-Ⅳ. The number of autophagic vesicles was significantly reduced， and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower （P<0.01）. The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were elevated （P<0.01）， while the expression level of LncRNA H19 was reduced （P<0.01）. Furthermore， the mRNA expression levels of PI3K， Akt， and mTOR increased （P<0.05， P<0.01）. ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.

Objective: To explore the distribution of traditional Chinese medicine (TCM) syndromes in children with hepatolenticular degeneration (Wilson disease, WD) based on factor analysis and cluster analysis. Methods: From November 2018 to November 2023, general information (gender, age of admission, age of onset, course of disease, clinical staging, Western medicine clinical symptoms, and family history) and TCM four-examination informations (symptoms and signs) were retrospectively collected from 757 cases of children with WD at the First Affiliated Hospital of Anhui University of Chinese Medicine, and factor analysis and cluster analysis were used to investigate TCM syndromes in children with WD. Results: A total of 757 children with WD were included, of which 483 were male and 274 were female; the median age at admission was 12.58 years, the median age at onset was 8.33 years, and the median course of disease was 24.37 months; clinical typing result indicated 506 cases of hepatic type, 133 cases of brain type, 99 cases of mixed-type, and 19 cases of other type; 36.46% of the children had no clinical symptoms (elevated aminotransferases or abnormalities in copper biochemistry); a total of 177 cases had a definite family history, and 10 cases had a suspected family history. Forty-three TCM four-examination information were obtained, with the top 10 in descending order being feeling listless and weak, brown urine, slow action, inappetence, dim complexion, slurred speech, angular salivation, body weight loss, hand and foot tremors, and abdominal fullness. In children with WD, the syndrome element of disease location was primarily characterized by the liver, involving the spleen and kidney, and the syndrome elements of disease nature were characterized by dampness, heat, and yin deficiency. Based on factor analysis and cluster analysis, five TCM syndromes were derived, which were, in order, syndrome of dampness-heat accumulation (265 cases, 35.01%), syndrome of yin deficiency of the liver and kidney (202 cases, 26.68%), syndrome of liver hyperactivity with spleen deficiency (185 cases, 24.44%), syndrome of qi and blood deficiency (79 cases, 10.44%), and syndrome of yang deficiency of the spleen and kidney (26 cases, 3.43%). Conclusion The TCM syndromes of children with WD were primarily syndromes of dampness-heat accumulation, yin deficiency of the liver and kidney, and liver hyperactivity with spleen deficiency. The liver was the main disease location, and the disease nature was characterized by deficiency in origin and excess in superficiality, excess and deficiency mixed. These findings suggest that treating children with WD should be based on the liver while also considering the spleen and kidney.

ObjectiveTo study the correlations between traditional Chinese medicine （TCM） syndromes and lipid metabolism in children with Wilson disease （WD）. MethodsClinical data and lipid metabolism indicators ［total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， apolipoprotein A1 （ApoA1）， apolipoprotein B （ApoB）， and lipoprotein a （Lpa）］ were retrospectively collected from 341 children with WD. The clinical data were compared among WD children with different syndromes， and the correlations between TCM syndromes and lipid metabolism in children with WD were analyzed. Least absolute shrinkage and selection operator （LASSO） regression was used for variable screening， and unordered multinomial Logistic regression was employed to analyze the effects of lipid metabolism indicators on TCM syndromes. ResultsThe 341 children with WD included 121 （35.5%） children with the dampness-heat accumulation syndrome， 103 （30.2%） children with the liver-kidney Yin deficiency syndrome， 68 children with the combined phlegm and stasis syndrome， 29 children with the spleen-kidney Yang deficiency syndrome， and 20 children with the liver qi stagnation syndrome. The liver-kidney Yin deficiency syndrome， combined phlegm and stasis syndrome， and spleen-kidney Yang deficiency syndrome had correlations with the levels of lipid metabolism indicators （P<0.05）. Lipid metabolism abnormalities occurred in 232 （68.0%） children， including hypertriglyceridemia （108）， hypercholesterolemia （23）， mixed hyperlipidemia （67）， lipoprotein a-hyperlipoproteinemia （12）， and hypo-HDL-cholesterolemia （22）. The percentages of hypertriglyceridemia and hypo-HDL-cholesterolemia varied among children with different TCM syndromes （P<0.05）. Correlations existed for the liver-kidney Yin deficiency syndrome with TG， TC， and HDL-C， the combined phlegm and stasis syndrome with TG， the spleen-kidney Yang deficiency syndrome with TG， TC， and LDL-C， and the liver Qi stagnation syndrome with TC and LDL-C （P<0.05， P<0.01）. ConclusionThe TCM syndromes of children with WD are dominated by the dampness-heat accumulation syndrome and the liver-kidney Yin deficiency syndrome， and dyslipidemia in the children with WD is dominated by hypertriglyceridemia and mixed hyperlipidemia. There are different correlations between TCM syndromes and lipid metabolism indicators， among which TG， TC， LDL-C， and HDL-C could assist in identifying TCM syndromes in children with WD.

Objective To investigate the types of diseases examined by ultrasonography in a certain island clinic,and to summarize the experience of ultrasound medical support in island area.Methods The ultrasound examination results of patients who were admitted to a certain island clinic from January 2017 to August 2022 were reviewed,and the types and characteristics of diseases examined by ultrasound were analyzed.Results A total of 2 043 patients underwent ultrasound examination.There were 76 disease categories and 1 579 diseases.The top five diseases were fatty liver(13.24%),kidney crystals(12.10%),kidney stones(10.70%),gallbladder polyps(6.33%)and ureteral stones with hydronephrosis(6.02%).Ultrasound could predict the pathological types of appendicitis and guide the clinical decision by observing the width of the appendiceal lumen and the layers of the appendiceal wall.Doppler-assessed ureteric jet could be used to determine the renal function of the affected side of ureteral calculi.Conclusion There are wide and varied disease categories in islands.Sonographers should have comprehensive abilities and qualities.This study can provide reference for the follow-up medical support on island area.

Objective To investigate the expression of long non-coding RNA maternally expressed gene 3(lncRNA MEG3)and autophagy in the liver of copper-loaded rats treated with Gandouling(GDL)and to explore its mechanism of action in attenuating liver fi-brosis.Methods Ten SD rats were taken as the normal group,and another 50 were divided into model groups,penicillamine group,GDL low dose group,GDL medium dose group,and GDL high dose group,with 10 rats in each group.The liver fibrosis model of rats with copper-loaded Wilson's Disease was established by gavage of copper sulphate pentahydrate.HE and Masson's staining were used to observe liver pathological morphology.ELISA was used to detect the levels of hyaluronic acid(HA),and laminin(LN),type Ⅲ procol-lagen(PC-Ⅲ),and type Ⅳ collagen(C-Ⅳ).A biochemical kit was used to detect the activity of alanine aminotransferase(ALT)and azelaic acid aminotransferase(AST).Western blot was used to detect the expression of alpha-smooth muscle actin(α-SMA)and collagen type Ⅰ(Col-Ⅰ).RT-qPCR was used to detect the expression of Beclin-1 and lncRNA Meg3mRNA.Immunofluorescence was used to detect the expression of Beclin-1 and LC3-Ⅱ.Results Compared with the normal group,rats in the model group showed collagen fiber deposition in liver tissue,increased levels of HA,LN,PC-Ⅲ,C-Ⅳ,α-SMA,Col-Ⅰ,liver injury,decreased ex-pression of lncRNA Meg3,and increased levels of key markers of autophagy,Beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ).After administration of GDL and penicillamine,comparing to the model groups,the levels of AST,LN,Col-Ⅰ,and Beclin-1 showed a trend of reduction in both GDL low,medium,and high dose groups and penicillamine group(P＜0.01).The levels of C-Ⅳ,and α-SMA were decreased in the GDL medium,low,and high dose group and the penicillamine group,with a significant re-duction in the GDL medium and high dose group(GDL low dose group:P＜0.05,GDL middle-high dose group:P＜0.01).Moreover,the reduced expression of lncRNA Meg3 was reversed,and the level of lncRNA Meg3 was increased in the GDL middle-high dose group and the penicillamine group(P＜0.01).Pathological section results indicated that the degree of liver fibrosis was reduced in rats after GDL intervention,and the effect of GDL was obvious in the high dose group.Conclusion GDL alleviated liver fibrosis,and the mecha-nism may be related to the regulation of autophagy expression by lncRNA Meg3.

Objective By observing the clinical efficacy of Zhinao capsule in the treatment of Parkinson's disease with mild cognitive impairment(PD-MCI)patients,we also explored the potential mechanism using network pharmacology and molecular docking technology,with the aim of providing a new idea for the treatment of PD-MCI with traditional Chinese medicine.Methods Random number table method was applied to divide the control group and test group into 35 cases each.Parkinson's disease basic treatment plan was used in the control group,and Zhinao capsule was added in the test group.The observation course was determined to be 8 weeks.The Montreal Cognitive Assessment(MoCA)score,MDS-Unified Parkinson's Disease Rating Scale(MDS-UPDRS)Ⅰ,Ⅱ and Ⅲ,PD Traditional Chinese Medicine(PD-TCM),and safety-related indexes were completed before treatment and at the end of the 8th week of treatment.The network pharmacology method was used to obtain the targets related to Zhinao capsules and PD-MCI.Constructed and analyzed the"drug-component-target"network.Analysis of"drug-disease"intersecting targets and enrichment of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways was obtained using R language.Protein-protein interaction(PPI)networks were constructed using Cytoscape 3.9.1.Finally,molecular docking was conducted.Results The MoCA score of the test group was remarkably greater than that of the control group after treatment(P<0.05);and the TCM syndrome score were noticeably below that of the control group(P<0.05).The test group showed a notable increase in the mean value of MoCA scale scores,and a clear decrease in the MDS-UPDRS Ⅰand PD-TCM before and after treatment(P<0.05).The MDS-UPDRS Ⅱ and Ⅲ scale scores of the test and control groups decreased to different degrees after treatment,but there was no significant difference(P>0.05).Zhinao capsules for PD-MCI treatment has calycosin,quercetin,kaempferol,etc.as core active ingredients,and TNF,IL-1β,IL-6,etc.as core targets.Molecular docking results also showed better binding of the core target to the active ingredient.Zhinao capsules regulates the expression of PPAR,cGMP-PKG,Oxytocin and other signaling pathway-related genes.Conclusion The Zhinao capsules can improve the cognitive function of PD-MCI patients,and the mechanism may be related to the fact that the components such as calycosin,quercetin,and kaempferol act on the targets such as TNF,IL-1β,and IL-6,and mediate the signaling pathways such as PPAR,cGMP-PKG,and Oxytocin.

Objective By observing the clinical efficacy of Zhinao capsule in the treatment of Parkinson's disease with mild cognitive impairment(PD-MCI)patients,we also explored the potential mechanism using network pharmacology and molecular docking technology,with the aim of providing a new idea for the treatment of PD-MCI with traditional Chinese medicine.Methods Random number table method was applied to divide the control group and test group into 35 cases each.Parkinson's disease basic treatment plan was used in the control group,and Zhinao capsule was added in the test group.The observation course was determined to be 8 weeks.The Montreal Cognitive Assessment(MoCA)score,MDS-Unified Parkinson's Disease Rating Scale(MDS-UPDRS)Ⅰ,Ⅱ and Ⅲ,PD Traditional Chinese Medicine(PD-TCM),and safety-related indexes were completed before treatment and at the end of the 8th week of treatment.The network pharmacology method was used to obtain the targets related to Zhinao capsules and PD-MCI.Constructed and analyzed the"drug-component-target"network.Analysis of"drug-disease"intersecting targets and enrichment of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways was obtained using R language.Protein-protein interaction(PPI)networks were constructed using Cytoscape 3.9.1.Finally,molecular docking was conducted.Results The MoCA score of the test group was remarkably greater than that of the control group after treatment(P<0.05);and the TCM syndrome score were noticeably below that of the control group(P<0.05).The test group showed a notable increase in the mean value of MoCA scale scores,and a clear decrease in the MDS-UPDRS Ⅰand PD-TCM before and after treatment(P<0.05).The MDS-UPDRS Ⅱ and Ⅲ scale scores of the test and control groups decreased to different degrees after treatment,but there was no significant difference(P>0.05).Zhinao capsules for PD-MCI treatment has calycosin,quercetin,kaempferol,etc.as core active ingredients,and TNF,IL-1β,IL-6,etc.as core targets.Molecular docking results also showed better binding of the core target to the active ingredient.Zhinao capsules regulates the expression of PPAR,cGMP-PKG,Oxytocin and other signaling pathway-related genes.Conclusion The Zhinao capsules can improve the cognitive function of PD-MCI patients,and the mechanism may be related to the fact that the components such as calycosin,quercetin,and kaempferol act on the targets such as TNF,IL-1β,and IL-6,and mediate the signaling pathways such as PPAR,cGMP-PKG,and Oxytocin.

Objective To investigate the expression of long non-coding RNA maternally expressed gene 3(lncRNA MEG3)and autophagy in the liver of copper-loaded rats treated with Gandouling(GDL)and to explore its mechanism of action in attenuating liver fi-brosis.Methods Ten SD rats were taken as the normal group,and another 50 were divided into model groups,penicillamine group,GDL low dose group,GDL medium dose group,and GDL high dose group,with 10 rats in each group.The liver fibrosis model of rats with copper-loaded Wilson's Disease was established by gavage of copper sulphate pentahydrate.HE and Masson's staining were used to observe liver pathological morphology.ELISA was used to detect the levels of hyaluronic acid(HA),and laminin(LN),type Ⅲ procol-lagen(PC-Ⅲ),and type Ⅳ collagen(C-Ⅳ).A biochemical kit was used to detect the activity of alanine aminotransferase(ALT)and azelaic acid aminotransferase(AST).Western blot was used to detect the expression of alpha-smooth muscle actin(α-SMA)and collagen type Ⅰ(Col-Ⅰ).RT-qPCR was used to detect the expression of Beclin-1 and lncRNA Meg3mRNA.Immunofluorescence was used to detect the expression of Beclin-1 and LC3-Ⅱ.Results Compared with the normal group,rats in the model group showed collagen fiber deposition in liver tissue,increased levels of HA,LN,PC-Ⅲ,C-Ⅳ,α-SMA,Col-Ⅰ,liver injury,decreased ex-pression of lncRNA Meg3,and increased levels of key markers of autophagy,Beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ).After administration of GDL and penicillamine,comparing to the model groups,the levels of AST,LN,Col-Ⅰ,and Beclin-1 showed a trend of reduction in both GDL low,medium,and high dose groups and penicillamine group(P＜0.01).The levels of C-Ⅳ,and α-SMA were decreased in the GDL medium,low,and high dose group and the penicillamine group,with a significant re-duction in the GDL medium and high dose group(GDL low dose group:P＜0.05,GDL middle-high dose group:P＜0.01).Moreover,the reduced expression of lncRNA Meg3 was reversed,and the level of lncRNA Meg3 was increased in the GDL middle-high dose group and the penicillamine group(P＜0.01).Pathological section results indicated that the degree of liver fibrosis was reduced in rats after GDL intervention,and the effect of GDL was obvious in the high dose group.Conclusion GDL alleviated liver fibrosis,and the mecha-nism may be related to the regulation of autophagy expression by lncRNA Meg3.

In order to further promote the reform of medical service price and strengthen the macro management of medical service price, the author constructed a calculation method for price adjustment space of medical service. This study was centered on two parameters of the historical base and the growth coefficient, to calculate the total amountof price adjustment. The historical base used the total revenue of medical services in the region from the previous year, and the growth coefficient was measured by two methods, the comprehensive indicator method and the consumer price index (CPI) reference method.Taking Suzhou, a national pilot city, as an example, the historical base in 2022 was 18 754 million yuan. By using the comprehensive indicator method, the annual growth coefficient was calculated to be 2.38%, and adjustment space of medical service price was 446.35 million yuan; According to the CPI reference method, the growth coefficient of Suzhou was 2.10%, and adjustment space of medical service price was 393.83 million yuan.The two methods for calculating the total amount each have their own advantages and disadvantages, and need to be further optimized and improved by drawing on the practical experience of reform in each pilot city.

【Objective】 To evaluate the efficacy and safety of ureteroscope or flexible ureteroscope combined with balloon dilatation in the treatment of ureteral stricture with renal calculi in transplanted kidney. 【Methods】 The clinical data of 9 patients treated in our hospital during 2016 and 2022 were reviewed. The changes of the width of hydronephrosis, levels of creatinine and urea nitrogen, reoperation, and re-dwelling of stents were analyzed. 【Results】 One patient failed the operation because the guide wire could not be inserted, and the other 8 patients successfully completed the surgery. The stents were removed 6 to 8 weeks after surgery. During the follow-up of 8 to 48 months, no recurrence of renal calculi occurred; 5 patients had no recurrence of ureteral stricture; 3 patients (cases 4, 6, 9) underwent regular ureteral stent replacement due to hydronephrosis; the width of hydronephrosis, creatinine and urea nitrogen levels of 8 patients were significantly improved (P<0.05). 【Conclusion】 Ureteroscope/flexible with balloon dilatation is safe and effective in the treatment of transplanted kidney with ureteral stricture and kidney stones.