Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

BackgroundPatients with colorectal cancer are frequently comorbid with depression， which severely affects the quality of life and treatment compliance， while compromising the efficacy of anticancer treament and prognosis. Current therapeutic strategies still have notable limitations， particularly the lack of systematic and targeted synergistic regimens that integrate oncological management and anti-depressive intervention. It is of great clinical significance to explore a safe and effective new comprehensive intervention protocol and clarify its underlying mechanism of action. ObjectiveTo explore the effectiveness and safety of Shugan Yunpi Decoction in alleviating depressive and anxiety symptoms in colorectal cancer patients with depressive disorder through the PI3K-AKT signaling pathway， in order to provide references for the comprehensive treatment of colorectal cancer and depressive disorder. MethodsThis study was a randomized controlled trial. A total of 106 patients admitted to the Baoding No.1 Hospital of traditional Chinese medicine from November 2023 to July 2025 were enrolled， who met the diagnostic criteria for the Chinese protocol of diagnosis and treatment of colorectal cancer （2023 edition） and the diagnostic criteria for depressive disorder as specified in the Chinese Classification and Diagnostic Criteria of Mental Disease， third edition （CCMD-3）. Patients were divided into the study group and the control group using a random number table， with 53 cases in each group. The control group received conventional chemotherapy combined with traditional Chinese medicine five-element music therapy， while the study group received conventional chemotherapy combined with Shugan Yunpi Decoction therapy. Both groups were treated for 8 weeks. Depressive and anxiety symptoms were assessed using the Hamilton Depression Scale-17 item（HAMD-17） and Hamilton Anxiety Scale （HAMA）， respectively. Western blot protein immunoblotting was used to detect the expression levels of PI3K， AKT， and pAKT. Real-time fluorescence quantitative reverse transcription polymerase chain reaction （qRT-PCR） was used to detect the expression levels of PI3K mRNA and AKT mRNA. Adverse reactions were recorded using a self-designed adverse reaction record form. ResultsRepeated measures analysis of variance showed that the time effects （F=139.336， 234.747）， group effects （F=43.900， 101.266）， and time-group interaction effects （F=13.409， 43.216） for HAMD-17 and HAMA scores in both groups were statistically significant （P<0.01）. After 4 and 8 weeks of treatment， the HAMD-17 and HAMA scores in both groups were lower than those before treatment， with statistically significant differences （P<0.05）. HAMD-17 and HAMA scores in the study group were lower than those in the control group （P<0.05）. The time effects （F=571.356， 309.266， 414.492）， group effects （F=6.901， 26.361， 39.362）， and time-group interaction effects （F=18.592， 19.266， 33.484） for the protein expression levels of PI3K， AKT， and pAKT in both groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the protein expression levels of PI3K and pAKT in the study group were lower than those in the control group， while the AKT protein expression level was higher than that in the control group（P<0.01）. The time effects （F=338.555， 225.059）， group effects （F=5.429， 9.726）， and time-group interaction effects （F=12.953， 21.214） for PI3K mRNA and AKT mRNA expression levels in two groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the expression levels of PI3K mRNA and AKT mRNA in the study group were lower than those in the control group （P<0.05）. The incidence of adverse reactions in the study group was lower than that in the control group （χ²=4.810， P<0.05）. ConclusionShugan Yunpi Decoction may help to ameliorate depressive and anxiety symptoms in colorectal cancer patients with depressive disorder by regulating the PI3K-AKT signaling pathway， decreasing the levels of PI3K， pAKT， PI3K mRNA， and AKT mRNA， with a favorable safety profile. ［Funded by Baoding City Science and Technology Planning Project （number， 2341ZF291）］

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

The patient, an 11-year-old girl, was admitted with recurrent fever for 20 days, worsening with abdominal distension for 7 days. Upon admission, she presented with recurrent fever, lymphadenopathy, hepatosplenomegaly, polyserositis, and multiple organ dysfunction. Lymph node pathology and clinical manifestations confirmed the diagnosis of idiopathic multicentric Castleman disease-TAFRO syndrome. Treatment with siltuximab combined with glucocorticoids was initiated, followed by maintenance therapy with tocilizumab. The patient is currently in complete clinical remission. Therefore, once a child is diagnosed with idiopathic multicentric Castleman disease -TAFRO syndrome, early use of siltuximab should be considered for rapid disease control, followed by tocilizumab for maintenance therapy.
Humans ; Castleman Disease/drug therapy* ; Child ; Antibodies, Monoclonal, Humanized/administration & dosage* ; Female ; Antibodies, Monoclonal/administration & dosage*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective To investigate the rehabilitation efficacy of Beckman oral-motor training combined with auditory integration training(AIT)in children with language development delay.Methods A total of 118 children diagnosed with language development delay were enrolled in this study,and randomly assigned to auditory training group or combined training group,with 59 cases in each group.Children in the auditory training group received AIT,while those in the combined train-ing group underwent Beckman oral-motor training combined with AIT.The clinical efficacy,intellec-tual development,language ability,oral motor function,articulation ability,and serum neurotrophic factor levels of the two groups were observed and compared.Results After treatment,the overall ef-fective rate in the combined training group was 93.22％(55/59),which was significantly higher than 79.66％(47/59)in the auditory training group,with a statistically significant difference(P＜0.05).Following treatment,the scores of intellectual development,language ability,oral motor function,and articulation ability,as well as the serum levels of brain-derived neurotrophic factor(BDNF)and nerve growth factor(NGF)in both groups were elevated compared to the pre-treatment levels.Moreover,these parameters in the combined training group were superior to those in the audi-tory training group,and the differences were statistically significant(P＜0.05).Conclusion Beck-man oral-motor training combined with AIT can enhance the rehabilitation outcome in children with language development delay,improving their speech function,intellectual development,oral motor function,articulation ability,and serum neurotrophic factor levels.

Objective To construct a nursing follow-up checklist for patients undergoing autologous hematopoietic stem cell transplantation,providing a basis for postoperative follow-up care.Methods Using evidence-based methods,the literature from major guide websites and databases using Chinese and English search terms was retrieved,and their quality was evaluated.The relevant items were extracted,and a first draft was formed.15 experts were selected in relevant fields from 14 tertiary hospitals in 13 provinces,cities,and autonomous regions across the country for Delphi inquiry.The nursing follow-up checklist was revised again based on expert opinions and clinical practice.The nursing follow-up checklist was initially applied and then revised again to form the final draft.Results 15 experts include 12 undergraduate and 3 master's degree holders.The positivity coefficients of the 2 rounds of inquiry were 100％;the authority coefficients of the experts were 0.815;the Kendall coefficients were 0.119 and 0.144,respectively;the differences were statistically significant(P＜0.001).The final nursing follow-up checklist was formed,which includes 6 primary indicators,including physiological status,psychological status,social and family support,living conditions,disease knowledge,and laboratory tests.19 patients(95％)found the follow-up content to be comprehensive.The follow-up nurses's satisfaction rate exceeded 85％.There were 27 secondary indicators and 61 tertiary indicators,with coefficients of variation of all indicators less than 0.25.Conclusion The nursing follow-up checklist is scientific,reliable,and practical,which can provide a basis for clinical nursing staff to follow up and comprehensively manage patients after autologous hematopoietic stem cell transplantation.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.