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 compare the hepatic bile acid profile between a mouse model of metabolic-associated steatohepatitis （MASH） induced by a high-fat， high-sugar， and high-cholesterol diet combined with intraperitoneal injection of 10% carbon tetrachloride （CCl₄） and MASH cases in clinical practice， and to investigate the feasibility of this model in studying drug interventions on bile acid profile in MASH. MethodsA total of 30 male C57BL/6J mice were randomly divided into control group and model group， with 15 mice in each group. The mice in the control group were given normal diet and drinking water and weekly injections of olive oil， and those in the model group were given a high-fat， high-sugar， and high-cholesterol diet， high-sugar drinking water， and weekly injections of CCl₄+olive oil. At the end of weeks 8， 12， and 16， 5 mice were selected from each group to collect samples. Behavioral assessments were performed， and body weight and liver wet weight were measured； liver pathology and lipid deposition were evaluated by HE staining， SAF scoring， oil Red O staining， the semi-quantitative analysis of stained area， the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， and liver triglyceride （TG） content； Sirius Red staining was performed for liver tissue to assess liver fibrosis； ultra-performance liquid chromatography-tandem mass spectrometry and targeted metabolomics were used to measure the hepatic bile acid profile， including cholic acid （CA）， glycocholic acid （GCA）， chenodeoxycholic acid （CDCA）， glycochenodeoxycholic acid （GCDCA）， ursodeoxycholic acid （UDCA）， tauroursodeoxycholic acid （TUDCA）， hyodeoxycholic acid （HDCA）， and glycodeoxycholic acid （GDCA）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the control group at the same time point， the model group had disheveled and dull fur， reduced activity， and relatively slow reactions at weeks 8， 12， and 16， as well as significant increases in liver wet weight （P<0.05）， the serum level of ALT （P<0.05）， the content of TG in the liver （P<0.05）， and SAF score （P<0.05）. As for the differentially expressed bile acids in liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， HDCA， and GDCA （all P<0.05）； compared with the control group at week 12， the model group had significantly higher levels of CA， GCA， CDCA， and GCDCA and significantly lower levels of UDCA and HDCA （all P<0.05）； compared with the control group at week 16， the model group had significantly higher levels of CA， GCA， CDCA， GCDCA， and TUDCA and significantly lower levels of UDCA， HDCA， and GDCA （all P<0.05）. As for the differentially expressed bile acids in the bile acid pool of liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， GDCA， and HDCA （all P<0.05）； compared with the control group at weeks 12 and 16， the model group had significantly higher levels of GCA and GCDCA and significantly lower levels of UDCA， GDCA， and HDCA （all P<0.05）. ConclusionThere are significant changes in the hepatic bile acid profile in a mouse model of MASH induced by a high-fat， high-sugar， and high-cholesterol diet combined with CCl₄， which are similar to the changes in bile acids in MASH cases in clinical practice， suggesting that this model can be used to explore the interventional effect of drugs on the bile acid profile in MASH.

Objective To investigate the current situation and existing problems regarding the diagnosis and treatment integrating traditional Chinese and western medicine in the emergency departments of various general hospitals in China to provide a reference for the development of integrated traditional Chinese and western medicine emergency medicine. Methods From November 18,2022 to February 28,2023,an online questionnaire survey was conducted among 291 hospitals in 21 provinces/municipalities directly under the Central Government across the country,which was based on the members of the Emergency Medicine Professional Committee of the Chinese Association of the Integration of Traditional Chinese and Western Medicine. The questionnaire covered 5 aspects:basic information of hospitals and emergency departments,personnel allocation,medical quality management,equipment allocation,and traditional Chinese medicine techniques and skills (including the application of traditional Chinese medicine and non-drug treatment of traditional Chinese medicine). A comparative study was carried out between the "hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine" and "western medicine hospitals" on the current situation of integrated traditional Chinese and western medicine diagnosis and treatment in the emergency department. Results A total of 291 valid questionnaires were collected,covering 291 hospitals in 21 provinces and municipalities directly under the Central Government across the country. Among them,142 were hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine,and 149 were western medicine hospitals. The number of doctors in the emergency departments of hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine were significantly less than that of western medicine hospitals[individuals:11.00 (7.00,18.75) vs. 20.00 (13.00,31.00),P<0.01]. Specifically,the numbers of traditional Chinese medicine doctors,integrated traditional Chinese and western medicine doctors,and "western medicine doctors learning traditional Chinese medicine" in these hospitals were significantly higher than those in western medicine hospitals[individuals:4.00 (2.00,9.00) vs. 0.00 (0.00,0.00),1.00 (0.00,4.00) vs. 0.00 (0.00,0.00),2.00 (0.00,5.00) vs. 0.00 (0.00,0.00),all P<0.01],while the number of western medicine doctors was significantly less than that in western medicine hospitals[individuals:4.00 (1.00,7.50) vs. 25.50 (16.00,37.00),P<0.01]. The number of nurses in the emergency departments of hospitals of traditional Chinese medicine and integrated traditional Chinese was significantly less than that of western medicine hospitals[individuals:23.00 (16.00,38.75) vs. 42.00 (30.00,80.00),P<0.01]. The numbers of traditional Chinese medicine nurses,"western medicine nurses learning traditional Chinese medicine" in these hospitals were also significantly higher than those in western medicine hospitals[individuals:1.50 (0.00,5.75) vs. 0.00 (0.00,0.00),1.00 (0.00,7.75) vs. 0.00 (0.00,0.00),all P<0.01],while the number of western medicine nurses was significantly less than that in western medicine hospitals[individuals:15.00 (9.00,25.00) vs. 42.00 (27.00,79.00),P<0.01]. In the situation of medical quality management,the setting rates of emergency clinics,resuscitation rooms and observation rooms in western medicine hospitals were close to those in hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine,but the setting rates of emergency department wards and emergency intensive care units (EICU) and the number of beds were significantly higher than those in hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine[setting rate of emergency department wards:70.47％ vs. 53.52％,setting rate of EICU:67.11％ vs. 47.89％,number of beds (individuals):18.00 (0.00,30.00) vs. 2.00 (0.00,12.00) and 8.00 (0.00,12.00) vs. 0.50 (0.00,7.00),all P<0.01]. In terms of the number of visits in 2022,the annual total number of emergency visits (10000 person-times) in western medicine hospitals:6.60 (3.38,12.00) vs. 4.00 (1.25,7.00),the number of visits to the resuscitation room (10000 person-times):0.40 (0.12,1.00) vs. 0.17 (0.05,0.50) and the annual discharge volume of EICU (number of case):216.00 (0.00,550.00) vs. 0.00 (0.00,187.50) were all higher than those in hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine (all P<0.01). In addition,the success rate of rescue in hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine was similar to that in western medicine hospitals,and the participation rate of traditional Chinese medicine in the treatment of the resuscitation room was significantly higher than that in western medicine hospitals (P<0.01). In the situation of equipment allocation,hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine had fewer numbers of equipment than western medicine hospitals (all P<0.01). The proportion of hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine equipped with non-drug treatment equipment of traditional Chinese medicine was significantly higher than that of western medicine hospitals (all P<0.01). In the application of traditional Chinese medicine techniques and skills,the proportions of hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine in using Chinese patent medicines,agreed prescriptions,syndrome differentiation and treatment prescriptions,etc. were all higher than those of western medicine hospitals (application rate of Chinese patent medicines:81.69％ vs. 61.74％,application rate of agreed prescriptions:61.97％ vs. 16.78％,application rate of syndrome differentiation and treatment prescriptions:61.27％ vs. 19.46％,all P<0.01). The application rates of decoction pieces,non-decoction agreed with prescriptions,injections,hospital preparations and other dosage forms in hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine were all significantly higher than those in western medicine hospitals (application rate of decoction pieces:29.58％ vs. 4.70％,the application rate of non-decoction agreed prescriptions:40.85％ vs. 7.38％,application rate of injections:80.28％ vs. 53.02％,application rate of hospital preparations:33.80％ vs. 12.75％,all P<0.01). The application proportions of oral administration,nasal feeding,enema,gastric lavage,external use,intravenous injection,etc. in hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine were all higher than those in western medicine hospitals (oral application rate:71.13％ vs. 42.28％,nasal feeding application rate:47.18％ vs. 26.17％,enema application rate:48.59％ vs. 19.46％,gastric lavage application rate:21.13％ vs. 6.04％,external use application rate:53.52％ vs. 16.78％,intravenous injection application rate:71.83％ vs. 54.36％,all P<0.01). The application proportions of some drugs such as Shenmai/Shengmai injection,Tianma injection in hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine were higher than those in western medicine hospitals (application rate of Shenmai/Shengmai injection:59.15％ vs. 35.57％,application rate of Tianma injection:40.85％ vs. 10.07％,application rate of Danshen Honghua injection:30.99％ vs. 14.77％,application rate of Angong Niuhuang pill:26.76％ vs. 12.08％,P<0.01). The proportions of hospitals of traditional Chinese medicine and integrated traditional Chinese and western medicine in carrying out traditional Chinese medicine non-drug treatment operations such as acupuncture,acupoint application,cupping,scraping,bone-setting,moxibustion,press needles,collateral pricking method,etc. were higher than those in western medicine hospitals (application rate of acupuncture:65.49％ vs. 11.41％,application rate of acupoint application:60.56％ vs. 10.07％,application rate of cupping:32.39％ vs. 4.70％,application rate of scraping:28.17％ vs. 2.01％,application rate of bone-setting:26.76％ vs. 10.74％,application rate of moxibustion:24.65％ vs. 5.37％,application rate of press needles:17.61％ vs. 1.34％,application rate of collateral pricking method:16.90％ vs. 0.67％,all P<0.01). Conclusion The proportion of integrated traditional Chinese and western medicine personnel in the emergency departments of hospitals in China is relatively low,and the utilization rate and equipment rate of non-drug treatment of traditional Chinese medicine and traditional Chinese medicine emergency drugs are not high. It is necessary to strengthen the cultivation of integrated traditional Chinese and western medicine skills of emergency department doctors and the application of non-drug treatment of traditional Chinese medicine and traditional Chinese medicine emergency drugs to improve the ability of integrated traditional Chinese and western medicine emergency treatment.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

Objective To investigate the clinical value of fiber nasopharyngoscope applied in adenoid hypertrophy(AH)combined with allergic rhinitis(AR)in children.Methods Clinical data of 174 pediatric patients from January 2021 to March 2024 was collected and analyzed.Among them,129 cases were diagnosed with AH via fiber nasopharyngoscope examination(79 cases with AR were assigned to the AH with AR group,the remaining 50 cases of simple AH without AR were assigned to the AH group),and 45 cases of simple AR without AH through fiber nasopharyngoscope examination were assigned to the AR group.And 25 healthy children who came to our pediatric health department for health examinations during the same period were selected as the healthy control(HC)group.On the day of admission,all subjects underwent lateral X-ray examination of the nasopharynx,and the ratio of the maximum thickness of adenoids to the anterior posterior diameter of the nasopharynx cavity(A/N ratio)was calculated.Meanwhile their of peripheral blood eosinophil(EOS)percentage,serum interleukin-17(IL-17),and tumor necrosis factor-α(TNF-α)levels were tested.The A/N ratio,peripheral blood EOS percentage,serum IL-17 and TNF-α levels were compared among the AH with AR group,AH group,AR group,and HC group.The A/N ratio,peripheral blood EOS percentage,serum IL-17 and TNF-α levels of children with different degrees of adenoid obstruction under fiber nasopharyngoscope were compared in AH and AR group.Spearman correlation coefficient was used to analyze the correlation between the degree of adenoid obstruction under fiber nasopharyngoscope and the levels of peripheral blood EOS percentage,serum IL-17 and TNF-α in children from AH and AR group.Result A/N ratio:the value in AH with AR group was higher than that in AH group(P＜0.05),the value in AH group was higher than that in AR group(P＜0.05),and the value in AR group was higher than that in HC group(P＜0.05).Peripheral blood EOS percentage,serum IL-17 and TNF-α levels:AH with AR group had higher levels than those in AR group(P＜0.05),AR group had higher levels than those in AH group(P＜0.05),and AH group had higher levels than those in HC group(P＜0.05).The A/N ratio,peripheral blood EOS percentage,serum IL-17 and TNF-α levels in children with adenoid obstruction degree Ⅲ～Ⅳ under fiber nasopharyngoscope in the AH group were significantly higher than those in children with degree Ⅰ～Ⅱ(P＜0.05).Spearman correlation analysis showed that the degree of adenoid obstruction under fiber nasopharyngoscope in children with AH accompanied by AR significantly positively correlated with peripheral blood EOS percentage,serum IL-17 and TNF-α levels(r values were 0.527,0.451,and 0.402 respectively,P＜0.05).Conclusion Fiber nasopharyngoscope can be used for the diagnosis of AH with AR in children,and can be positive in determining severity of the patient's condition when combined with peripheral blood EOS percentage,serum IL-17 and TNF-α levels.

Objective:To explore the latent classes of fear of childbirth in late pregnancy women and its relationship with sense of coherence, providing reference for precise support interventions in clinical practice.Methods:From January to September 2023, convenience sampling was used to select 304 pregnant women who underwent antenatal examination at the Obstetrics Clinic of Affiliated Hospital of Hangzhou Normal University as participants. The General Information Questionnaire, Childbirth Attitudes Questionnaire, and the Sense of Coherence Scale-13 (SOC-13) were used for questionnaire survey. Latent profile analysis was used to explore the categories of fear of childbirth in late pregnancy women, and analyzed differences of SOC-13 scores among women with different categories of fear of childbirth.Results:Fear of childbirth in 304 late pregnant women was divided into three latent classes, including low-level fear group of (50.0%, 152/304), moderate-level fear group of (35.2%, 107/304), and high-level fear group of (14.8%, 45/304). ANOVA analysis showed that there were statistically significant differences in total score and dimension scores of SOC-13 among late pregnancy women with three different classes of fear of childbirth ( P<0.05) . Conclusions:There are three latent classes of fear of childbirth in late pregnancy women. The sense of coherence among pregnant women affects their fear of childbirth. Nursing staff should address the heterogeneity of fear of childbirth in late pregnancy women, starting from sense of coherence, and take targeted intervention measures to reduce the fear of childbirth in late pregnancy women.

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹcollagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.

Wilson's disease （WD） is a copper metabolism disorder caused by mutations in the ATP7B gene， with diverse phenotypes and complex pathogenesis. It is one of the few rare diseases that can achieve good clinical efficacy through standardized treatment. Since there are few systematic reviews of this disease， we summarize the pathogenesis and treatment methods of WD from traditional Chinese and western medicine by reviewing the literature related to WD. In western medicine， ATP7B gene mutation is considered as the root cause of WD， which affects copper transport and causes copper metabolism disorders. The excessive copper deposited in the body will result in oxidative stress， defects in mitochondrial function， and cell death. Western medicine treatment of WD relies mainly on drugs， and copper antagonists are the first choice in clinical practice， which are often combined with hepatoprotective and antioxidant therapy. Surgery is a common therapy for the patients with end-stage WD， and gene therapy provides an option for WD patients. According to the traditional Chinese medicine （TCM） theory， WD is rooted in constitutional deficiency and copper accumulation and triggered by dampness-heat accumulation or phlegm combined with stasis. The patient syndrome varies in different stages of the disease， and thus the treatment should be based on syndrome differentiation. The TCM treatment method of nourishing the liver and kidneys and warming the spleen and kidneys can address the root cause. The methods of clearing heat and drying dampness， resolving phlegm and dispelling stasis， and soothing liver and regulating qi movement can be adopted to treat symptoms. On the basis of syndrome differentiation， special prescriptions for the treatment of WD have been formulated， such as Gandou decoction， Gandouling， and Gandou Fumu decoction， which have been widely used in clinical practice. TCM and western medicine have their own advantages and shortcomings. The integrated Chinese and western medicine complementing with each other demonstrates great therapeutic potential. This paper summarizes the pathogenesis and treatment of WD with integrated Chinese and western medicine， aiming to provide a reference for the clinical diagnosis and treatment of this disease.

ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction （GDFMD） in the development of liver fibrosis in Wilson's disease （WD）. MethodFirst， 30 TX-j mice were randomly divided into the model group， high-dose， medium-dose， and low-dose GDFMD groups， and penicillamine group， with six mice in each group， and another six wild-type mice were used as the normal group. The high-dose， medium-dose， and low-dose GDFMD groups were intragastrically administered drugs of 13.92， 6.96， 3.48 g·kg^-1. In the penicillamine group， 0.1 g·kg^-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline， once a day， for four consecutive weeks. Samples were collected four weeks after gavage， and enzyme-linked immunosorbent assay （ELISA） was used to detect type Ⅲ procollagen peptide （PCⅢ）， collagen type Ⅳ （Col Ⅳ）， hyaluronic acid （HA）， and laminin （LN）. Hematoxylin-eosin （HE）， Masson， and picric acid-Sirus red collagen （Sirus Red） staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry， and Western blot were used to observe the expressions of α-smooth muscle actin （α-SMA） and collagen type Ⅰ （Col Ⅰ）， which were related to the activation of hepatic stellate cells （HSCs）. The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 （ULK1） and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group， the four items of liver fibrosis （PCⅢ， Col Ⅳ， HA， and LN） in the model group were significantly abnormal （P<0.01）， and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated （P<0.05， P<0.01）， and miR-29b-3p expression was down-regulated （P<0.01）. ULK1， p-ULK1， autophagy-related gene 13 （Atg13）， p-Atg13， Beclin-1， FAK family kinase-interacting protein of 200 kDa （FIP200）， activating molecule in BECN1-regulated autophagy protein 1 （AMBKA1）， and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ） were up-regulated （P<0.05， P<0.01）. p62 protein expression was down-regulated （P<0.01）. Compared with the model group， the four items of liver fibrosis in the high-dose， medium-dose， and low-dose GDFMD groups and the penicillamine group were significantly improve （P<0.01）， and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated （P<0.05， P<0.01）， and the expression of miR-29b-3p was up-regulated （P<0.01）. ULK1， p-ULK1， Atg13， p-Atg13， Beclin-1， FIP200， AMBKA1， and LC3Ⅱ/Ⅰ were down-regulated （P<0.05， P<0.01）， and p62 protein expression was up-regulated （P<0.01）. The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured （P<0.01）. ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.

Objective:To systematically evaluate the correlation between maternal arsenic exposure during pregnancy and congenital heart disease (CHD) in offspring.Methods:Literature search was performed through databases such as PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and VIP.com to include epidemiological literature on association between maternal arsenic exposure during pregnancy and offspring CHD published domestically and internationally. The search was conducted from database establishment until November 2, 2022. Stata MP15 software was used for meta-analysis of binary variables, and I 2 statistics and Q test were used for heterogeneity test, fixed effect model or random effect model was selected based on the test results. Using OR value (95% CI) as the effect evaluation indicator, subgroup analysis was conducted based on CHD subtypes [conotruncal defects (CTD), atrioventricular septal defect (AVSD), total anomalous pulmonary venous return (TAPVR), left ventricular outflow tract obstruction (LVOTO), right ventricular outflow tract obstruction (RVOTO), atrial septal defect (ASD)/ventricular septal defect (VSD), and patent ductus arteriosus (PDA)]. Results:Nine articles were finally included, including two Chinese and seven English articles. Among them, 8 articles had CHD as the outcome, 5 articles had ASD/VSD as the outcome, 4 articles had CTD as the outcome, 3 articles had LVOTO as the outcome, 2 articles had PDA as the outcome, and 1 article had RVOTO as the outcome. An analysis was conducted on 8 articles with CHD as the outcome. After heterogeneity testing, I 2 = 88.5% and P < 0.001, indicating significant heterogeneity. A random effect model was used for meta-analysis, and the combined OR value (95% CI) was 1.51 (1.40 - 1.62). The results of CHD subgroup analysis showed that the combined OR values (95% CI) for ASD/VSD, CTD, LVOTO, PDA, and RVOTO were 1.68 (1.53 - 1.84), 1.64 (1.29 - 2.09), 2.89 (1.82 - 4.61), 1.78 (1.53 - 2.08), and 0.81 (0.64 - 1.03), respectively. Conclusion:Maternal arsenic exposure during pregnancy is associated with development of offspring CHD, including ASD/VSD, CTD, LVOTO, and PDA as the common lesions in offspring CHD.