This article systematically reviews and compares the major international English consensus statements/guidelines on the diagnosis and treatment of Wilson disease published since 2022， with a focus on the recommendations from multidisciplinary expert consensus statements/guidelines. These consensus statements/guidelines mainly include the multidisciplinary treatment guidelines issued by the American Association for the Study of Liver Diseases in 2022， the clinical practice guidelines released by the European Union （European Association for the Study of the Liver/European Reference Network） in 2025， and the practice guidelines published by the British Association for Studies of the Liver in 2022， and comparative analysis and summarization were performed with reference to the 2025 edition of Chinese Multidisciplinary Expert Consensus on Orphan/Anticopper Drugs and Other Non-drug Management of Hepatolenticular Degeneration （CMEC-HLD）. Overall， the core content remained basically consistent between the guidelines of the European Union， the US， and the UK and CMEC-HLD， while many details varied due to the differences in experiences and research advances across these countries. Globally， there is still a lack of truly meaningful medical guideline for Wilson disease driven by evidence-based medicine， which requires further research and international cooperation among peers in the future.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective To analyze the clinical efficacy of transcatheter tricuspid valve replacement (TTVR) in cardiac implantable electronic lead-related tricuspid regurgitation (TR). Methods The patients with severe TR who underwent LuX-Valve TTVR in 9 Chinese medical centers from June 2020 to August 2021 were retrospectively enrolled. They were divided into a cardiac implantable electronic device (CIED) group and a non-CIED group based on whether they had pre-existing CIED implantation. Success of the procedure was defined as safe implantation of the LuX-Valve and complete withdrawal of the delivery system. Prognostic improvement was defined as a decrease of TR grade to≤2+ and an improvement of cardiac function by≥2 grades. Surgical success and postoperative prognosis were compared between the two groups. Results A total of 190 patients were collected, including 50 males and 140 females with a mean age of 66.2±7.8 years. There were 29 patients in the CIED group, and 161 patients in the non-CIED group. In the CIED group, 28 patients were implanted with a permanent pacemaker and 1 patient with a cardioverter-defibrillator. Preoperative New York Heart Association (NYHA) cardiac function class, TR degree, left ventricular ejection fraction, tricuspid annular plane systolic excusion, and cardiac risk scores were comparable between the two groups (P>0.05). Postoperative TR was reduced to≤2+ in all patients, and there was no statistical difference in the incidence of perivalvular leakage between the two groups (P=0.270). Postoperative CT of CIED patients showed the valve was in place, and the lead was not extruded, twisted, or deflected. The in-hospital mortality of the two groups were 10.3% and 1.9%, respectively, and the difference was statistically significant (P=0.047). In addition, there was no statistical difference between the two groups in terms of postoperative improvement of cardiac function and mortality in the 1- and 2-year follow-up. Conclusion TTVR is feasible, safe, and effective in patients with CIED implantation, and the pre-existing lead has no significant effect on the clinical efficacy.

It is believed that children bronchiolitis obliterans （BO） is located at the lung and closely related to the spleen and kidney. Phlegm， stasis， block and deficiency are the main pathogenesis. This article promotes staged differentiation and treatment of BO considering the clinical manifestations and pathogenesis characteristics. The attack stage is dominated by phlegm and stasis blocking the lung， for which the method of dissolving phlegm and dispelling stasis， relieving cough and calming panting should be used； Xiaoqinglong Decoction（小青龙汤） and Sanzi Yangqin Decoction （三子养亲汤） with modifications and selfmade Modified Wuhu Decoction （五虎汤加味） are recommended for cold-phlegm blocking the lung syndrome and phlegm heat blocking the lung syndrome， respectively. In sustained stage， the upper excess and lower deficiency together with phlegm-stasis blocking the lung are the pathogenesis， for which the method of dissolving phlegm and dispelling stasis， reopening the block and supplementing deficiency is suggested， and Xiaoqinglong Decotion （小青龙汤） and Duqi pills （都气丸） with modifications can be used. In convalescent stage， the pathogenesis is lung-spleen-kidney depletion with residual pathogen. It suggested to supplement the deficiency and consolidate the root， as well as clear the residual pathogen， for which Baogen NO.1 Decoction （宝根1号方） with modifications can be used.

Objective:A nationwide multi-center and large sample survey was conducted to compare the validity of the Mini International Neuropsychiatric Interview (Hypo-) Manic Episode with Mixed Features-DSM-5 Module (MINI-M) questionnaire and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier (CUDOS-M) depression subscale in identifying mixed features in patients experiencing (hypo-) manic episodes.Methods:Using a convenience sampling method, 366 patients with bipolar disorder experiencing acute (hypo-) manic episodes who met the inclusion and exclusion criteria were recruited. The diagnosis of "with mixed features" was based on the DSM-5 criteria for mixed features. The predictive validity of the MINI-M questionnaire and the CUDOS-M depression subscale to screen mixed features was analyzed using the receiver operating characteristic (ROC) curve. Additionally, the difference in area under the ROC curve (AUC) between the two instruments was compared.Results:The AUC for the MINI-M questionnaire and the CUDOS-M depression subscale in screening mixed features were 0.79 (95 %CI=0.75-0.84) and 0.81 (95 %CI=0.77-0.86), respectively. There was no statistically significant difference in AUC between the two measurements ( Z=-1.19, P>0.05). Among patients with acute (hypo-) manic episodes, 45.9% (168/366) presented with mixed features according to the DSM-5 criteria, while the corresponding figures were 43.7% (160/366) using the MINI-M questionnaire (total score≥3) and 42.1% (154/366) using the CUDOS-M depression subscale (total score≥20). Screening results were comparable among the three measures. Conclusion:Mixed features are common among patients experiencing acute (hypo-) manic episodes. The MINI-M questionnaire and the CUDOS-M depression subscale demonstrate equivalent validity in identifying mixed features.

Objective To explore the predictive value of cystatin C(Cys C),high mobility group box 1(HMGB1),and growth differentiation factor-15(GDF-15)levels for early infection after flap reconstruction for diabetic foot ulcer(DFU).Methods From July 2021 to March 2024,155 DFU patients treated in our hospital were included in DFU group.DFU patients were assigned into non-infection group(104 cases)and infection group(51 cases)according to whether there was infection at the operation site within one week after flap reconstruction.Control group included 85 patients with diabetes but without foot ulcer.Latex immunoturbidimetry was applied to detect serum Cys C level;enzyme linked immunosorbent assay to detect serum levels of HMGB1 and GDF-15;multivariate logistic regression to analyze the factors affecting early infection after flap reconstructionfor DFU,and receiver operating characteristic(ROC)curve to analyze the predictive value of serum Cys C,HMGB1,and GDF-15 levels for early infection after flap reconstruction for DFU.Results The expression levels of serum Cys C,HMGB1,and GDF-15 were obviously higher in the DFU group(P＜0.05)when compared with those in the control group.The expression levels of FPG,CRP,Cys C,HMGB1,and GDF-15 were obviously higher in the infection group(P＜0.05)when compared with those in the non-infection group.Cys C,HMGB1,GDF-15,FPG,and CRP were all inde-pendent risk factors for early infection after flap reconstruction for DFU(P＜0.05).The AUC predicted by serum Cys C,HMGB1,and GDF-15 alone for early infection after flap reconstruction for DFU was 0.810,0.850,and 0.828,respectively.The AUC predicted by the combination of these three markers was 0.930,which was better than that predicted by the three markers alone(ZCysC-three combination=3.381,ZHMGB1-three combination=2.588,ZGDF-15-three combination=2.857,all P＜0.05).Conclusions Cys C,HMGB1,and GDF-15 are upregulated in the serum of DFU patients,and all the three are factors affecting early infection after flap reconstruction for DFU.The combination of the three has high predictive value for early infection after DFU flap repair.

Objective To explore the predictive value of cystatin C(Cys C),high mobility group box 1(HMGB1),and growth differentiation factor-15(GDF-15)levels for early infection after flap reconstruction for diabetic foot ulcer(DFU).Methods From July 2021 to March 2024,155 DFU patients treated in our hospital were included in DFU group.DFU patients were assigned into non-infection group(104 cases)and infection group(51 cases)according to whether there was infection at the operation site within one week after flap reconstruction.Control group included 85 patients with diabetes but without foot ulcer.Latex immunoturbidimetry was applied to detect serum Cys C level;enzyme linked immunosorbent assay to detect serum levels of HMGB1 and GDF-15;multivariate logistic regression to analyze the factors affecting early infection after flap reconstructionfor DFU,and receiver operating characteristic(ROC)curve to analyze the predictive value of serum Cys C,HMGB1,and GDF-15 levels for early infection after flap reconstruction for DFU.Results The expression levels of serum Cys C,HMGB1,and GDF-15 were obviously higher in the DFU group(P＜0.05)when compared with those in the control group.The expression levels of FPG,CRP,Cys C,HMGB1,and GDF-15 were obviously higher in the infection group(P＜0.05)when compared with those in the non-infection group.Cys C,HMGB1,GDF-15,FPG,and CRP were all inde-pendent risk factors for early infection after flap reconstruction for DFU(P＜0.05).The AUC predicted by serum Cys C,HMGB1,and GDF-15 alone for early infection after flap reconstruction for DFU was 0.810,0.850,and 0.828,respectively.The AUC predicted by the combination of these three markers was 0.930,which was better than that predicted by the three markers alone(ZCysC-three combination=3.381,ZHMGB1-three combination=2.588,ZGDF-15-three combination=2.857,all P＜0.05).Conclusions Cys C,HMGB1,and GDF-15 are upregulated in the serum of DFU patients,and all the three are factors affecting early infection after flap reconstruction for DFU.The combination of the three has high predictive value for early infection after DFU flap repair.

Objective:A nationwide multi-center and large sample survey was conducted to compare the validity of the Mini International Neuropsychiatric Interview (Hypo-) Manic Episode with Mixed Features-DSM-5 Module (MINI-M) questionnaire and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier (CUDOS-M) depression subscale in identifying mixed features in patients experiencing (hypo-) manic episodes.Methods:Using a convenience sampling method, 366 patients with bipolar disorder experiencing acute (hypo-) manic episodes who met the inclusion and exclusion criteria were recruited. The diagnosis of "with mixed features" was based on the DSM-5 criteria for mixed features. The predictive validity of the MINI-M questionnaire and the CUDOS-M depression subscale to screen mixed features was analyzed using the receiver operating characteristic (ROC) curve. Additionally, the difference in area under the ROC curve (AUC) between the two instruments was compared.Results:The AUC for the MINI-M questionnaire and the CUDOS-M depression subscale in screening mixed features were 0.79 (95 %CI=0.75-0.84) and 0.81 (95 %CI=0.77-0.86), respectively. There was no statistically significant difference in AUC between the two measurements ( Z=-1.19, P>0.05). Among patients with acute (hypo-) manic episodes, 45.9% (168/366) presented with mixed features according to the DSM-5 criteria, while the corresponding figures were 43.7% (160/366) using the MINI-M questionnaire (total score≥3) and 42.1% (154/366) using the CUDOS-M depression subscale (total score≥20). Screening results were comparable among the three measures. Conclusion:Mixed features are common among patients experiencing acute (hypo-) manic episodes. The MINI-M questionnaire and the CUDOS-M depression subscale demonstrate equivalent validity in identifying mixed features.

ObjectiveTo explore effect of modified Wuhutang on airway inflammation and expression of mucin （Muc） 5AC， signal transducer and activator of transcription 3 （STAT3）， nuclear factor kappa B （NF-κB）， and NOD-like receptor thermal protein domain associated protein 3 （NLRP3） in respiratory syncytial virus （RSV）-infected asthmatic mice. MethodSeventy male BALB/c mice of 6-8 weeks old were randomized into normal control （CON）， asthma （ovalbumin， OVA）， RSV infection-induced asthma （OVA+RSV）， high-， medium-， and low-dose （4.08， 2.04， 1.02 g·kg^-1·d^-1， respectively） modified Wuhutang， and dexamethasone （Dxms， 0.1 g·kg^-1d^-1） groups （n=10）. The model of asthma was established by sensitization and atomization inhalation with OVA. The RSV infection-induced asthma model was established by three consecutive RSV nasal infusions （1.0 × 10⁶ PFU·mL^-1， 50 μL）. Wuhutang was administrated by gavage， and Dxms by intraperitoneal injection. The CON group was given the same amount of normal saline by gavage. The mice were anesthetized with 2.5% pentobarbital sodium 24 h after the last administration， and then the lung tissue was stained by hematoxylin-eosin （HE） and Van Gieson （VG） for observation of airway inflammation. The immunohistochemical assay was employed to detect the expression of Muc5AC. Western blot was employed to determine the protein levels of phosphorylated （p）-STAT3， STAT3， p-NF-κB， NF-κB， and NLRP3. ResultCompared with the CON group， the OVA group presented airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition. The OVA+RSV group showed severer airway inflammatory cell infiltration and tissue hyperemia and edema than the OVA group. Compared with the OVA+RSV group， modified Wuhutang alleviated the airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition， and the high-dose group had the best performance. Compared with the CON group， the OVA group and the OVA+RSV group showed increased expression level of Muc5AC （P<0.01）. Compared with the OVA+RSV group， modified Wuhutang reduced the expression level of Muc5AC， and the reduction was significant in the high-dose group （P<0.05）. Compared with the high-dose modified Wuhutang group， Dxms lowered the expression level of Muc5AC （P<0.05）. Compared with the CON group， the OVA and OVA+RSV groups showed up-regulated protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.05， P<0.01）. Compared with the OVA+RSV group， modified Wuhutang down-regulated the protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.01）. Compared with the high-dose modified Wuhutang group， the Dxms group showed up-regulated levels of p-STAT3， p-NF-κB proteins （P<0.01）. ConclusionModified Wuhutang can reduce airway inflammation and down-regulate the expression of Muc5AC， p-STAT3， p-NF-κB， and NLRP3 in RSV-infected asthmatic mice， which suggests that Wuhutang reduces airway inflammation in RSV-infected asthma by regulating the STAT3/NF-κB signaling pathway.

Objective To investigate the expression levels of HBV pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in circulating serum of chronic hepatitis B (CHB) patients after withdrawal from nucleos(t)ide analogues (NUC), as well as the correlation of HBV pgRNA and HBcrAg levels in circulating blood in different periods of time with recurrence in CHB patients after drug withdrawal. Methods Among the patients who attended the outpatient service of Affiliated Hospital of North Sichuan Medical College from December 2019 to July 2022, a total of 108 CHB patients who received anti-HBV therapy for at least 5 years and met the criteria for drug withdrawal in 2017 EASL Guidelines were enrolled. According to the time of drug withdrawal, the patients were divided into 4-, 12-, and 24-week groups after drug withdrawal, and according to the presence or absence of recurrence, they were divided into recurrence group and non-recurrence group. Quantitative real-time PCR was used to measure the level of HBV pgRNA in circulating serum of CHB patients; ELISA was used to measure the expression level of HBcrAg in peripheral venous blood; quantitative real-time PCR was used to measure HBV DNA load with high accuracy. The t -test was used for comparison of continuous data between two groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Pearson correlation test was used to investigate the correlation between the indices in circulating blood. Results For the CHB patients after drug withdrawal, the recurrence rate was 17.1% at 4-12 weeks, cumulative recurrence rate reached 29.3% after 24 weeks of follow-up, the patients with positive HBV DNA alone accounted for 64.3% and 60.0%, respectively, those with positive HBeAg alone accounted for 28.5% and 20.0%, respectively, and those with positive HBV DNA and HBeAg accounted for 7.1% and 20.0%, respectively. The expression levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum of CHB patients at 24 weeks after drug withdrawal were significantly higher than those at the time of drug withdrawal and at 4 weeks after drug withdrawal, and there was a significant difference between groups at different time points (all P < 0.05). Compared with the non-recurrence group, the recurrence group had significantly higher expression levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum ( t =2.549, 8.654, and 27.429, all P < 0.05), and further analysis of the recurrence group showed that the levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum at 12-24 weeks were significantly higher than those at 4-12 weeks (all P < 0.05). At the time of drug withdrawal, the recurrence group had significantly higher expression levels of HBV pgRNA and HBcrAg in circulating serum than the non-recurrence group ( t =18.561 and 6.152, both P < 0.001). The Pearson correlation analysis showed that in the recurrence group after drug withdrawal, HBV pgRNA and HBcrAg were positively correlated with HBV DNA in circulating serum ( r =0.82 and 0.66, both P < 0.001), while no such correlation was observed in the non-recurrence group ( r =0.14 and 0.04, both P > 0.05). Conclusion The recurrence group had significantly higher expression levels of HBV pgRNA and HBcrAg than the non-recurrence group at the time of drug withdrawal, suggesting that the levels of HBV pgRNA and HBcrAg in the CHB patients of the non-recurrence group at the time of drug withdrawal may be used as the reference thresholds for safe drug withdrawal in CHB patients, and measurement of HBV pgRNA and HBcrAg may be one of the potential reference indicators for the selection of anti-HBV treatment endpoints in the future.