Primary biliary cholangitis （PBC） is an autoimmune liver disease characterized by intrahepatic cholestasis， while fatigue is a common symptom of PBC that significantly affects the quality of life of patients. The pathogenesis of fatigue is complex and may be associated with the factors such as cholestasis-induced inflammation， gut microbiota dysbiosis， brain structural and functional abnormalities， and mitochondrial dysfunction. At present， first-line therapies and liver transplantation have a limited effect in alleviating fatigue， and there is still a lack of standardized comprehensive assessment system. Emerging drugs and non-pharmaceutical interventions， including lifestyle modifications， have shown potential application prospects. This article systematically reviews the research advances in the clinical manifestations， pathogenesis， clinical assessment， and intervention of fatigue in PBC patients， in order to provide a reference for optimizing treatment strategies and promoting the research and development of new therapies.

Lung transplantation is a definitive treatment for end-stage lung disease and can significantly improve patient prognosis. However, postoperative complications such as infection, rejection, ischemia-reperfusion injury and chronic lung allograft dysfunction intertwine to form a complex pathological network, posing persistent challenges to long-term patient survival. In 2025, research teams worldwide have made systematic progress in the field of basic lung transplantation research. By integrating cutting-edge technologies including single-cell multi-omics, spatial transcriptomics and novel animal models, significant breakthroughs have been achieved in the evolutionary dynamics of drug-resistant infections, molecular mechanisms of immune regulation, programmed cell death, optimization of donor lung protection strategies and early warning of chronic lung allograft dysfunction. This article systematically reviews the representative advances in basic lung transplantation research worldwide in 2025, and deeply analyzes the implications of mechanistic breakthroughs for optimizing diagnosis and treatment strategies, aiming to anchor the direction for innovative breakthroughs and clinical translation in basic lung transplantation research.

Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Progressive familial intrahepatic cholestasis type 8 (PFIC8). METHODS A child with PFIC diagnosed at Beijing Children's Hospital Affiliated to Capital Medical University in September 2025 was selected as the study subject. Peripheral venous blood samples were collected from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Beijing Children's Hospital Affiliated to Capital Medical University (Ethics No.: 2023-E-126-Y). RESULTS: The proband, a 2-month-old female infant, had manifested jaundice of the skin and sclera, and slightly distended abdomen. She had no visible abdominal wall varicose veins, soft abdomen, and no palpable masses. Biliary atresia was ruled out by intraoperative cholangiography. WES revealed that she has harbored compound heterozygous variants of KIF12 gene, namely c.809C>T (p.Ala270Val) and c.1313G>A (p.Arg438Lys), which were verified by Sanger sequencing to have derived from her mother and father, respectively. According to the ACMG guidelines, both variants were classified as variants of uncertain significance (VUS). Based on the pre-defined search strategy, 10 articles were retrieved, which involved 25 PFIC cases, including 5 from China. Together with the proband of this study, the 26 PFIC patients have primarily presented with high GGT cholestasis, with the genetic cause in all cases attributed to variants of the KIF12 gene. CONCLUSION The c.809C>T and c.1313G>A compound heterozygous variants of the KIF12 gene probably underlay the pathogenesis of cholestatic liver disease in this child. Above findings have enriched the mutational and phenotypic spectra of PFIC8.
Humans ; Kinesins/genetics* ; Female ; Cholestasis, Intrahepatic/genetics* ; Infant ; Heterozygote ; Mutation ; Exome Sequencing ; Male

Objective:To elucidate the correlation between phase angle and malnutrition and to determine the cut-off value for phase angle to predict malnutrition in pancreatic cancer patients.Methods:This prospective cross-sectional study enrolled patients with pancreatic cancer hospitalized in the Department of Hepato-pancreato biliary Surgery at Beijing Hospital between December 2021 and March 2024. Baseline data, diet survey results, and body composition of these patients were recorded. Phase angle was measured with the InBody 720(Biospace, Korea). The Global Leadership Initiative on Malnutrition (GLIM) criteria were used to diagnose malnutrition.Results:A total of 110 cases (75 males and 35 females) aged 29-87(63.00±12.37) years were included. The prevalence of malnutrition was 63.6% (70/111) among the patients. Patients were divided into malnutrition ( n=77) and non-malnutrition ( n=33) groups as per the GLIM criteria. Phase angle was significantly lower in the malnutrition group than in the non-malnutrition group ( t=-3.808, P<0.001). Positive correlations were found between phase angle and body mass index, appendicular skeletal muscle mass index, fat-free mass index , fat-free mass, total energy intake, total protein, albumin, and prealbumin (all P<0.05).After adjusting for sex and age, low phase Angle remained an independent risk factor for malnutrition ( OR=3.809, 95% CI: 1.150-12.612, P=0.029). The cut-off values of phase angle for predicting malnutrition were 4.43 for males (with a sensitivity of 0.955, specificity of 0.585, area under the curve of 0.636; 95% CI: 0.508-0.763, P=0.037) and 4.54 for females (with a sensitivity of 1.000, specificity of 0.708, area under the curve of 0.799; 95% CI: 0.653-0.946, P<0.001). Conclusion:Phase angle may serve as a valid and simple indicator of malnutrition in pancreatic cancer patients.

Objective To investigate the effect and underlying mechanism of miR-137 on athero-sclerosis(AS)plaques in apolipoprotein E(ApoE)gene knockout(ApoE)mice.Methods Sixty ApoE-/-mice were fed with high-fat diet for 12 weeks to establish an AS model.Then they were assigned into AS group,negative control group,miR-137 group,Ad negative control group,and combination group,with 12 mice in each group;Another 12 wild-type C57BL/6 mice fed with chow diet were subjected as the Control group.Fully automated biochemical analyzer was applied to detect serum lipid levels,including total cholesterol(TC),triglycerides(TG),low-density lipo-protein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C).ELISA was con-ducted to detect the levels of serum inflammatory factors,including TNF-α,IL-4,IL-6,and IL-10.HE staining was used to observe the morphological changes of mouse aortic tissue.Oil red O stai-ning was employed to observe the overall formation of aortic plaques.Immunofluorescence stai-ning was utilized to detect the expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)in the aortic tissue.Real-time qPCR was applied to detect the mRNA expression of miR-137 and sex determining region Y box protein 4(SOX4)in the aorta.Results The miR-137 group has significantly lower serum levels of TG,TC,LDL-C,TNF-α and IL-6,and higher levels of HDL-C,IL-10 and IL-4 when compared with the AS group and negative control group(P＜0.05).The combination treatment resulted in increased serum levels of TG,TC,LDL-C,TNF-αand IL-6,while decreased levels of HDL-C,IL-10 and IL-4 in comparison with the Ad negative control group(P＜0.05).Larger aortic plaque area,more severe overall aortic plaque injury and stronger iNOS fluorescence intensity were observed in the AS group than the control group(P＜0.05).Treatment of miR-137 reversed above histological changes,resulting in smaller aortic plaque area,attenuated overall aortic plaque injury,decreased iNOS fluorescence intensity,and elevated Arg-1 fluorescence intensity when compared with the AS group and negative control group(P＜0.05).Compared with the Ad negative control group,the aortic plaque area,overall aortic plaque injury and iNOS fluorescence intensity were increased,while the Arg-1 fluorescence intensity was significantly decreased in the combined group(P＜0.05).Double luciferase assay showed that the luciferase activity of SOX4-containing wild-type cells was significantly decreased after transfection of miR-137 mimics when compared with transfection of mimics negative control(0.37±0.05 vs 1.00±0.08,P＜0.05).Conclusion Overexpression of miR-137 inhibits the activa-tion of rat sarcoma/mitogen-activated protein kinase pathway probably by down-regulating SOX4 expression,and then suppress M1 macrophage polarization and promote M2 macrophage polariza-tion,reduces inflammatory response and the formation of AS plaques.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To investigate the changes in sympathetic nerve activity after lower limb immobilization and the role of sympathetic nerve in regulating disuse atrophy of skeletal muscles.Methods:The experiment was divided into the following 3 parts: ① Twelve 8-week-old male C57 mice were randomly divided into a blank control group and a hind limb fixation group ( n=6). The blank control group received no intervention while the hind limb fixation group received splint fixation of the hind limbs for 2 weeks before the musculoskeletal multi-dimensional characterization was completed at the behavioral, pathological and molecular levels. ② Thirty-six 8-week-old male C57 mice were selected and randomly divided into a control group and 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) ( n=6). The control group was fed normally until 14 days without any intervention while the 5 hind limb fixation groups were sampled after fixation for 1, 3, 5, 7 and 14 days, respectively. The level of norepinephrine in the serum and the expression level of tyrosine hydroxylase (TH), a marker of sympathetic nerve activity in the paraventricular nucleus of hypothalamus (PVN), were detected to observe the plasticity of sympathetic nerve activity. ③ Eighteen 8-week-old male C57 mice were selected and randomly divided into a blank control group, a hind limb fixation group and a hind limb fixation plus medication group ( n=6). The blank control group received no intervention while the 2 fixation groups were injected with phosphate buffer (PBS) and propranolol hydrochloride solution for 2 consecutive weeks, respectively. The parameters related to the skeletal muscles were compared between the 3 groups. Results:① Compared with the control group, the mass and function of skeletal muscles in the hind limb fixation group were statistically significantly decreased ( P<0.05). ② The levels of serum norepinephrine [(3.27±1.03) ng/mL, (9.21±1.05) ng/mL, (6.36±0.88) ng/mL, (3.84±1.00) ng/mL, and (3.91±0.75) ng/mL] and the PVN TH levels (42.00%±5.38%, 61.67%±5.57%, 55.82%±3.11%, 50.90%±2.53%, and 39.17%±9.07%) in the 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) were significantly higher than those in the control group [(1.81±0.72)] ng/mL and 23.33%±5.50%] ( P<0.05). ③ The wet weight of the gastrocnemius muscle [(93.50±4.32) mg] and the cross-section area of the tibial anterior muscle [(1,180.00±95.09) μm 2] in the hind limb fixation plus medication group were increased significantly compared with those in the hind limb fixation group [(80.83±9.99) mg and (907.80±121.00) μm 2] ( P<0.05). Conclusions:Overactivation of the sympathetic nervous system occurs in the mice model of skeletal muscle disuse atrophy after hind limb fixation. Inhibition of sympathetic nerve activity may reduce the severity of skeletal muscle atrophy at the lower limbs.

China is a high-incidence region for gastric cancer globally. The disease is characterized by a high morbidity rate, low early diagnostic rate, and poor long-term outcomes, imposing a significant burden on both patients and society. Therefore, exploring the pathogenesis of gastric cancer, developing novel therapeutic strategies, and identifying new drug targets is of great importance. Telomerase expression is broadly associated with cancer cell targeting, and its up-regulation is one of the key factors driving the initiation and progression of gastric cancer. Additionally, telomerase is intricately involved in the regulation of autophagy and autophagy-associated cell death. While autophagy can induce chemoresistance, excessive autophagy may lead to cell death, which also constitutes one of the mechanisms of chemotherapy. Telomerase not only directly contributes to gastric cancer pathogenesis but also indirectly influences its development and treatment by modulating autophagy and autophagic cell death. Therefore, telomerase holds promise as a novel therapeutic target in gastric cancer.
Humans ; Stomach Neoplasms/genetics* ; Telomerase/genetics* ; Autophagy/physiology*