Primary biliary cholangitis （PBC） is an autoimmune-mediated chronic cholestatic liver disease. Ursodeoxycholic acid （UDCA） is the first-line treatment drug for PBC， yet some patients with suboptimal biochemical response to UDCA face a significant increase in the risk of disease progression and often have a poor prognosis. This article systematically summarizes the currently established criteria for biochemical response and analyzes the factors and underlying mechanisms associated with suboptimal UDCA response from multiple perspectives including genetic background， demographic factors， immunological features， and the gut-liver axis. Furthermore， it outlines the available second-line treatment drugs and emerging therapies， in order to provide a basis for early identification of high-risk patients and optimization of treatment strategies， as well as a reference for future research directions.

[Objective] To investigate the infection and characteristics of hepatitis E virus among blood donors in Hangzhou. [Methods] A total of 5 075 blood samples of blood donors from Zhejiang Provincial Blood Center from September to November 2023 were collected, including 5 037 samples with normal ALT and 38 samples with elevated ALT (>50 U/L). Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-HEV IgM, anti-HEV IgG and HEV-Ag. The Fisher test and Chi-square test were used to evaluate the difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among different levels of ALT. The distribution characteristics of HEV screening in blood donors were analyzed. Univariate and multivariate logistic regression were used to analyze the susceptibility factors of anti-HEV IgM and anti-HEV IgG seropositivity, and the anti-HEV IgM-reactive blood donors were followed up by telephone. [Results] The reactivity rates of anti-HEV IgM, anti-HEV IgG and HEV-Ag in 5 075 blood samples were 0.45%, 22.98% and 0%, respectively. There was no difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among different levels of ALT (P>0.05), and the results of univariate and multivariate logistic regression analysis showed that age was a risk factor for anti-HEV IgM and anti-HEV IgG reactivity in blood donors (P<0.05), while no difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among blood donors was noticed in gender, occupation and education level (P>0.05). [Conclusion] There is a potential risk of transfusion-transmitted HEV (TT-HEV) in Hangzhou, and a cost-effective HEV screening strategy needs to be established to continue regular HEV surveillance in Hangzhou to assess the risk of infection.

Objective To explore the mechanism of Angong Niuhuang pill on the neurological function of rats with spontaneous intracerebral hemorrhage based on the tumor necrosis factor-α/nuclear factor-κB(TNF-α/NF-κB)signaling pathway combined with network pharmacology.Methods The targets for treatment of intracerebral hemorrhage with Angong Niuhuang pill were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),High-Throughput Experiment and Refeence-guided Database of Traditional Chinese Medicine(HERB).Key targets were screened for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and molecular docking.Then,rats were randomly divided into normal control group,model group,Angong Niuhuang pill group(administered by gavage at 270 mg·kg-1·d-1),and the Western medicine group(intraperitoneal injection of 4 500 mg·kg-1·d-1+furosemide 1.8 mg·kg-1·d-1),the dosage administered was the equivalent dose ratio calculated based on the body surface area for humans and animals.The intracerebral hemorrhage model was replicated by the autologous heart blood caudate nucleus injection method.After modeling,the neurological function behavior scores,brain tissue water content,pathological changes of brain tissue,blood-brain barrier permeability,and protein expression levels of NF-κB p65,tumor necrosis factor receptor 1(TNFR1),inhibitor NF-κBα(IκBα)and TNF-α in brain tissue of each group were observed.Results A total of 216 intersection genes were selected.The results of GO enrichment analysis and KEGG pathway annotation analysis predicted that the TNF-α/NF-κB inflammatory signaling pathway was one of the main regulatory pathways.The animal experiment results showed that at 72 hours after modeling,compared with the model group,the neurological function score,brain tissue water content,and blood-brain barrier permeability index evans blue(EB)content of the Angong Niuhuang pill group were significantly decreased[neurological function score:1.62±0.62 vs.2.23±0.58,brain water content:(77.7±0.49)%vs.(79.9±0.04)%,EB content(μg/L):490.50±100.79 vs.1 966.20±94.81,all P<0.05];the pathological observation of brain tissue showed that Angong Niuhuang pill could reduce the pathological damage of brain tissue around the hematoma,repair the blood-brain barrier,and alleviate brain edema;the Western blotting results showed that Angong Niuhuang pill could inhibit the protein expression of TNF-α,TNFR1,and NF-κB p65 in brain tissue[NF-κB p65 protein expresion(NF-κB p65/β-actin):2.27±0.52 vs.5.40±0.26;TNFR1 protein expression(TNFR1/β-actin):1.49±0.33 vs.2.52±0.04,TNF-α protein expression(TNF-α/β-actin):1.40±0.13 vs.2.29±0.18,all P<0.05],promote the protein expression of IκB-α(IκB-α/β-actin):0.78±0.02 vs.0.32±0.00,P<0.05).Conclusion Angong Niuhuang pill may regulate the TNF-α/NF-κB signaling pathway by inhibiting the expression of TNFR1 and promoting the expression of IκB-α,exerting neuroprotective effects.

The Screening Tool of Older Persons' Prescriptions(STOPP)and the Screening Tool to Alert to Right Treatment(START)play a crucial role in identifying potentially inappropriate prescriptions among the elderly.As the aging population continues to grow, there is an urgent need for effective tools to address the challenges of multimorbidity and polypharmacy in elderly patients in China.However, the development of rational medication screening tools has significantly lagged, and there is currently a lack of sensitive and effective instruments in China.This article analyzes the newly added entries in the third edition of STOPP/START, aiming to provide a reference for managing multiple medication regimens and for the development of relevant tools for elderly patients in China.

Objective To explore the mechanism of Angong Niuhuang pill on the neurological function of rats with spontaneous intracerebral hemorrhage based on the tumor necrosis factor-α/nuclear factor-κB(TNF-α/NF-κB)signaling pathway combined with network pharmacology.Methods The targets for treatment of intracerebral hemorrhage with Angong Niuhuang pill were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),High-Throughput Experiment and Refeence-guided Database of Traditional Chinese Medicine(HERB).Key targets were screened for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and molecular docking.Then,rats were randomly divided into normal control group,model group,Angong Niuhuang pill group(administered by gavage at 270 mg·kg-1·d-1),and the Western medicine group(intraperitoneal injection of 4 500 mg·kg-1·d-1+furosemide 1.8 mg·kg-1·d-1),the dosage administered was the equivalent dose ratio calculated based on the body surface area for humans and animals.The intracerebral hemorrhage model was replicated by the autologous heart blood caudate nucleus injection method.After modeling,the neurological function behavior scores,brain tissue water content,pathological changes of brain tissue,blood-brain barrier permeability,and protein expression levels of NF-κB p65,tumor necrosis factor receptor 1(TNFR1),inhibitor NF-κBα(IκBα)and TNF-α in brain tissue of each group were observed.Results A total of 216 intersection genes were selected.The results of GO enrichment analysis and KEGG pathway annotation analysis predicted that the TNF-α/NF-κB inflammatory signaling pathway was one of the main regulatory pathways.The animal experiment results showed that at 72 hours after modeling,compared with the model group,the neurological function score,brain tissue water content,and blood-brain barrier permeability index evans blue(EB)content of the Angong Niuhuang pill group were significantly decreased[neurological function score:1.62±0.62 vs.2.23±0.58,brain water content:(77.7±0.49)%vs.(79.9±0.04)%,EB content(μg/L):490.50±100.79 vs.1 966.20±94.81,all P<0.05];the pathological observation of brain tissue showed that Angong Niuhuang pill could reduce the pathological damage of brain tissue around the hematoma,repair the blood-brain barrier,and alleviate brain edema;the Western blotting results showed that Angong Niuhuang pill could inhibit the protein expression of TNF-α,TNFR1,and NF-κB p65 in brain tissue[NF-κB p65 protein expresion(NF-κB p65/β-actin):2.27±0.52 vs.5.40±0.26;TNFR1 protein expression(TNFR1/β-actin):1.49±0.33 vs.2.52±0.04,TNF-α protein expression(TNF-α/β-actin):1.40±0.13 vs.2.29±0.18,all P<0.05],promote the protein expression of IκB-α(IκB-α/β-actin):0.78±0.02 vs.0.32±0.00,P<0.05).Conclusion Angong Niuhuang pill may regulate the TNF-α/NF-κB signaling pathway by inhibiting the expression of TNFR1 and promoting the expression of IκB-α,exerting neuroprotective effects.

Mitochondria not only serve as the central hub for cellular energy metabolism,but also participate in crucial physiological processes such as signal transduction and activity regulation.Abnormal mitochondrial quantity,imbalance in mtDNA copy number,accumulation of genetic mutations,and aberrant activation of autophagic pathways can lead to mitochondrial dysfunction or even organelle disorders,while activating mechanisms of cellular damage and death,consequently contributing to the pathogenesis of various diseases.As a highly selective form of autophagy,mitophagy plays a pivotal regulatory role in organelle quality control and homeostasis maintenance.This article focuses on the classic PINK1/Parkin pathway-mediated mitophagy as an entry point,summarizing recent research advances regarding the role of mitophagy in neurodegenerative diseases,aiming to provide novel insights for developing targeted mitophagy regulation strategies to improve prevention and treatment approaches for neurodegenerative disorders.

BACKGROUND:Currently,the main purpose of surgical treatment for lumbar compression fractures is to improve symptoms,reduce pain,improve quality of life,minimize surgical risks,and reduce surgical exposure time.OBJECTIVE:To explore the safety and clinical efficacy of percutaneous vertebroplasty via Kambin's triangle in the treatment of senile spinal deformity accompanied by osteoporotic vertebral compression fractures.METHODS:A retrospective analysis was conducted on 31 patients with spinal deformity and osteoporotic vertebral compression fractures who were admitted to Tianjin Union Medical Center from January 2019 to December 2022.There were 21 males and 10 females,aged between 60 and 84(70.0±10.3)years old.The duration of illness ranged from 1 to 6(3.5±1.7)weeks.A total of 35 vertebral segments were affected.The distribution of vertebral compression fractures included:10 cases of L1 fracture,12 cases of L2 fracture,2 cases of L1+L2 fracture,5 cases of L3 fracture,and 2 cases of L1+L3 fracture.Based on the surgical approach,patients were divided into two groups:group A(via Kambin's triangle approach)with 15 cases,and group B(via traditional pedicle puncture)with 16 cases.Unilateral approach vertebroplasty was performed on both groups.The surgical duration,number of radiation exposures,presence of bone cement leakage,occurrence of complications such as nerve and vascular injuries were recorded in both groups.Postoperative CT scans were used to observe the dispersion and hardening of bone cement.RESULTS AND CONCLUSION:(1)In the group A,the surgical duration was 21-30 minutes per vertebra,with an average of(25.0±5.7)minutes.In the group B,the surgical duration was 25-43 minutes per vertebra,with an average of(33.0±7.2)minutes.The surgical duration for puncturing a single vertebra was significantly longer in the group B compared to the group A,with a statistically significant difference(P＜0.05).(2)The average number of radiation exposures per vertebra during surgery was(6.2±1.6)in the group A and(9.3±1.8)in the group B,with a statistically significant difference between the two groups(P＜0.05).(3)In the group A,no bone cement leakage was found.In group B,2 cases had bone cement leakage,and 1 case had bone cement entering the spinal canal,but no obvious neurological symptoms were observed.The leakage rate was 13％.Both groups had 1 case of subcutaneous hematoma.(4)Postoperative CT scans for observing the distribution of bone cement in the vertebral body showed that the rates of uniform dispersion of bone cement within the vertebrae were 71％and 33％in the groups A and B,respectively,with a statistically significant difference between the two groups(P＜0.05).(5)It is suggested that percutaneous vertebroplasty via Kambin's triangle approach offers advantages such as shorter surgical duration,better dispersion and filling of bone cement within the vertebrae,lower risk of complications,reduced radiation exposure,and satisfactory results with unilateral puncture.

Objective: To investigate hepatocellular carcinoma ( HCC ) risk factors in hepatitis B e antigen (HBeAg)-negative cirrhotics , and to develop and validate a predictive model using these indicators . Methods: A total of 649 hospitalized patients with HBeAg-negative hepatitis B cirrhosis and HBeAg-negative primary HCC were enrolled . Patients were randomly divided into a modeling group (n = 298) and a validation group (n = 351) at a 7 ∶3 ratio . Logistic regression analysis was used to screen for independent predictors of HCC occurrence . A predic- tive model was constructed and validated using receiver operating characteristic ( ROC) curves . The clinical net benefit of the prediction model was assessed via decision curve analysis . Results: Univariate analysis showed sig- nificant statistical differences between the modeling and validation groups in serum alanine aminotransferase (ALT) , aspartate aminotransferase ( AST) , triglycerides ( TG) , gamma-glutamyl transferase ( GGT) , red blood cell count (RBC) , hemoglobin (Hb) , platelet count (PLT) , international normalized ratio (INR) , alpha-feto- protein (AFP) , serum calcium (Ca2 + ) , serum cholinesterase (CHE) , and HBV DNA levels . Multivariate logistic regression analysis identified AST , GGT , Hb , PLT , Ca2 + , CHE , and HBV DNA as independent influencing fac- tors for HCC occurrence (P < 0. 05) , with OR (95% CI) of 1 . 002 ( 1 . 000 - 1 . 005) , 1 . 006 ( 1 . 003 - 1 . 008) , 0. 994 (0. 988 - 0. 999) , 0. 984 (0. 981 - 0. 988) , 9. 624 (3 . 821 - 24. 245 ) , 0. 999 (0. 987 - 0. 999) , and 7. 530 (4. 143 - 13 . 687) , respectively. A nomogram prediction model was established based on these seven indi- cators . The area under the ROC curve was 0. 936 in the modeling group and 0. 941 in the validation group . Cali- bration curves demonstrated high predictive accuracy of the nomogram. Conclusion AST , GGT , Hb , PLT , Ca2 + , CHE , and HBV DNA are independent risk factors for HCC development in patients with HBeAg-negative hepatitis B-related cirrhosis . The established non-invasive prediction model exhibits good discriminative ability and clinical utility , providing an experimental basis for early detection and preventive screening of HCC in this patient population .

BACKGROUND:Currently,the main purpose of surgical treatment for lumbar compression fractures is to improve symptoms,reduce pain,improve quality of life,minimize surgical risks,and reduce surgical exposure time.OBJECTIVE:To explore the safety and clinical efficacy of percutaneous vertebroplasty via Kambin's triangle in the treatment of senile spinal deformity accompanied by osteoporotic vertebral compression fractures.METHODS:A retrospective analysis was conducted on 31 patients with spinal deformity and osteoporotic vertebral compression fractures who were admitted to Tianjin Union Medical Center from January 2019 to December 2022.There were 21 males and 10 females,aged between 60 and 84(70.0±10.3)years old.The duration of illness ranged from 1 to 6(3.5±1.7)weeks.A total of 35 vertebral segments were affected.The distribution of vertebral compression fractures included:10 cases of L1 fracture,12 cases of L2 fracture,2 cases of L1+L2 fracture,5 cases of L3 fracture,and 2 cases of L1+L3 fracture.Based on the surgical approach,patients were divided into two groups:group A(via Kambin's triangle approach)with 15 cases,and group B(via traditional pedicle puncture)with 16 cases.Unilateral approach vertebroplasty was performed on both groups.The surgical duration,number of radiation exposures,presence of bone cement leakage,occurrence of complications such as nerve and vascular injuries were recorded in both groups.Postoperative CT scans were used to observe the dispersion and hardening of bone cement.RESULTS AND CONCLUSION:(1)In the group A,the surgical duration was 21-30 minutes per vertebra,with an average of(25.0±5.7)minutes.In the group B,the surgical duration was 25-43 minutes per vertebra,with an average of(33.0±7.2)minutes.The surgical duration for puncturing a single vertebra was significantly longer in the group B compared to the group A,with a statistically significant difference(P＜0.05).(2)The average number of radiation exposures per vertebra during surgery was(6.2±1.6)in the group A and(9.3±1.8)in the group B,with a statistically significant difference between the two groups(P＜0.05).(3)In the group A,no bone cement leakage was found.In group B,2 cases had bone cement leakage,and 1 case had bone cement entering the spinal canal,but no obvious neurological symptoms were observed.The leakage rate was 13％.Both groups had 1 case of subcutaneous hematoma.(4)Postoperative CT scans for observing the distribution of bone cement in the vertebral body showed that the rates of uniform dispersion of bone cement within the vertebrae were 71％and 33％in the groups A and B,respectively,with a statistically significant difference between the two groups(P＜0.05).(5)It is suggested that percutaneous vertebroplasty via Kambin's triangle approach offers advantages such as shorter surgical duration,better dispersion and filling of bone cement within the vertebrae,lower risk of complications,reduced radiation exposure,and satisfactory results with unilateral puncture.

The Screening Tool of Older Persons' Prescriptions(STOPP)and the Screening Tool to Alert to Right Treatment(START)play a crucial role in identifying potentially inappropriate prescriptions among the elderly.As the aging population continues to grow, there is an urgent need for effective tools to address the challenges of multimorbidity and polypharmacy in elderly patients in China.However, the development of rational medication screening tools has significantly lagged, and there is currently a lack of sensitive and effective instruments in China.This article analyzes the newly added entries in the third edition of STOPP/START, aiming to provide a reference for managing multiple medication regimens and for the development of relevant tools for elderly patients in China.