ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Objective To investigate the safety parameters of the air-powered electrocautery hook and its advantages in laparoscopic surgery.Methods In pressure trauma experiments,21 healthy New Zealand White Rabbits were randomly divided into three groups.In each group,three sites(liver,intestine,and kidney)were selected from each rabbit,and the air-powered electrocautery hook was used under laparoscopy to apply pressure and time gradients in a cross-combination manner.The three groups of experimental rabbits were dissected at three time points:immediately after application,3 d post-application,and 7 d post-application.Pathological sections were prepared from the corresponding treated sites,and the extent of injury was assessed.In rabbit renal capsule removal experiment,another 20 healthy New Zealand White Rabbits were randomly divided into 2 groups.Renal capsule removal was performed by using an air-powered electrosurgical hook and a conventional electrosurgical hook,respectively,to compare the two groups in terms of surgical time,intraoperative bleeding volume,intraoperative complications,and the number of times of wiping speculum.Results In pressure trauma experiment,except for the intestinal tract at 3 seconds(P=0.060),the histopathological scores under 0.3 MPa pressure were significantly higher than those under 0.1 MPa(P<0.05)and 0.2 MPa(P<0.05)in all the tissues.In the tissue sampling groups at 3 d and 7 d post-surgery,no tissue damage was observed in any tissue at any time point under 0.1 MPa pressure.In rabbit renal capsule removal experiment,the aerodynamic electrocautery group had less intraoperative bleeding volume than the conventional electrocautery group[(2.9±0.5)ml vs.(3.4±0.5)ml,t=-2.280,P=0.035].There were no significant differences between the two groups in terms of surgical time,intraoperative complication rates,and the number of times of wiping speculum(P>0.05).Conclusions The safe pressure range for using the air-powered electrosurgical hook on the surfaces of the kidney and intestinal tract is within 0.2 MPa.Within the safe pressure range,blowing on tissue for 6 seconds or less is relatively safe.Using the air-powered electrosurgical hook in surgeries requiring the separation of loose connective tissue can reduce intraoperative bleeding.

Objective To investigate the impact of phase Ⅱ cardiac rehabilitation on the rehabilitation needs and physical activity status of patients after coronary heart disease intervention.Methods A total of 90 patients with coronary heart disease who underwent percutaneous coronary intervention(PCI)in the Coronary Heart Disease Center of the hospital from August 2023 to August 2024 were selected as the research subjects.They were subjected to a 12-week standardized phase Ⅱ cardiac rehabilitation training.General data survey forms,cardiac rehabilitation scales,and the International Physical Activity Questionnaire were used for scale surveys to understand the patients' needs before and after rehabilitation and their weekly physical activity en-ergy expenditure.The cardiopulmonary exercise test gold standard,which reflects exercise capacity through three indicators-maximum oxygen uptake(VO2 max),anaerobic threshold(AT),and metabolic equivalents(MET),were used to compare the physical activity status before and after cardiac rehabilitation.Results Compared with before the implementation,after the implementation of cardiac rehabilitation,the autonomy score in-creased(21.36±1.85 vs.16.73±3.28),the process anxiety(12.60±3.87 vs.14.27±2.12)and outcome anxiety scores(2.31±1.76 vs.4.56±3.56)decreased,the level of low-intensity physical activity decreased[(2 711.62±1 487.09)min/week vs.(3 845.97±2 083.71)min/week],the levels of moderate-intensity[(1 314.67±783.54)min/week vs.(686.22±126.79)min/week],high-intensity[(1 861.33±798.27)min/week vs.(112.00±40.77)min/week],and total physical activity increased[(5 887.62±2 843.54)min/week vs.(4 644.19±2 287.16)min/week].The levels of VO2 max[(28.11±14.28)mL·min-1·kg-1 vs.(23.82±12.34)mL·min-1·kg-1],AT[(16.06±5.41)mL·min-1·kg-1 vs.(13.53±4.56)mL·min-1·kg-1],and MET[(6.89±1.59)mL·min-1·kg-1 vs.(5.78±1.21)mL·min-1·kg-1]all in-creased,with statistically significant differences(P＜0.05).Conclusion Phase Ⅱ rehabilitation after PCI can effectively improve patients' physical activity levels.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective To understand the trends in availability and usage for four non-statin lipid-lowering drugs between 2020 and 2023 in China,and to explore the impact of centralized drug procurement and national drug price negotiation policy on the accessibility and utilization trends of these medications.Methods Data processing was performed on four non-statin lipid-lowering drugs(ezetimibe,hybutimibeh,evolocumab,alirocumab)from over 1 000 hospitals within the China Pharmaceutical Association network units from 2020 to 2023 was performed on.SPSS 27.0 was employed for descriptive statistical analysis and x2 tests regarding drug availability,sales revenue,defined daily dose system(DDDs),and cost per DDD(DDDc).Results The availability and DDDs of four cholesterol absorption inhibitors or PCSK9-mAbs increased year by year during the study period,with the most significant increase observed in the first year after centralized drug procurement or national drug price negotiation policy.After the national drug price negotiation policy,alirocumab had the highest availability among the three negotiated drugs.The sales volume of ezetimibe,which was included in the centralized drug procurement program,increased before the negotiation but decreased significantly afterwards,with its share of sales declining year by year.During the study period,the sales volumes and market shares of the three negotiated drugs all increased annually,with evolocumab showing notably higher sales values and percentages than both hybutimibe and alirocumab after the negotiation.The DDDc for all four drugs continued to decrease during the survey period,with the first-year post-centralized drug procurement or national drug price negotiation policy witnessing the largest drop.Conclusion Both of the centralized drug procurement and the national drug price negotiation policy can significantly increase the accessibility to non-statin lipid-lowering drugs and promote their clinical application,however,there is a mismatch between the growth in usage and accessibility for certain varieties.

OBJECTIVE: Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS: Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS: Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals ; Psoriasis/chemically induced* ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Disease Models, Animal ; Cupping Therapy/methods* ; Signal Transduction ; Imiquimod ; Ion Channels/genetics* ; Male ; Mechanotransduction, Cellular

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling