Chronic heart failure （CHF） is a complex clinical syndrome caused by ventricular dysfunction， with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome， as the core pathogenesis of CHF， persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions， resulting in the accumulation of phlegm-fluid， blood stasis， and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention， forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang， the clinical experience of the traditional Chinese medicine （TCM） master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome， and achievements from molecular biological studies， this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild （Stage Ⅰ-Ⅱ）， severe （Stage Ⅲ）， and critical （Stage Ⅳ） stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical， pathophysiological， and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance， corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α（PGC-1α）/silent information regulator 2 homolog 1 （SIRT1） and ATPase activity. The severe stage centers on oxidative stress and structural damage， reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage， Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage， increase adenosine triphosphate （ATP） content， and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration， leading to the collapse of Yin-Yang equilibrium. At this stage， Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore （MPTP）， reduce cardiomyocyte apoptosis rate， and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF， this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

Objective To investigate the association of serum total testosterone(TT),free testosterone(FT),sex hormone-binding globulin(SHBG),and estradiol(E_2)with all-cause mortality rate(AMR)in males and to evaluate their predictive value. Methods Based on data from the National Health and Nutrition Examination Survey(NHANES)cycles(1999—2004 and 2013—2016),the relationships between different sex hormones and AMR was analyzed with Cox proportional hazards regression models. The dose-response relationships between different sex hormones and male AMR were assessed with restricted cubic splines(RCS). The predictive performances of different sex hormones for male AMR were compared with receiver operating characteristic(ROC)curves and the area under the curve(AUC). The survival differences across varying sex hormone levels were evaluated with Kaplan-Meier survival curves and log-rank tests. Results This study involved 3632 adult male participants with a median follow-up of 6.5 years,during which 320 AMR occurred(8.8%). Cox univariate analysis indicated that TT,FT and SHBG were risk factors for AMR(P＜0.001). Cox multivariate analysis revealed that FT and SHBG were independent risk factors for AMR(FT:HR=0.90,95%CI:0.86-0.94; SHBG:HR=1.01,95%CI:1.01-1.02). RCS revealed a U-shaped nonlinear relationship between TT,FT and AMR(P＜0.001); SHBG showed a positive dose-response relationship with AMR(P＜0.001). The AUCs of FT predicting the 5-year,10-year,and 15-year AMR were 0.78(95%CI:0.73-0.82),0.80(95%CI:0.76-0.84),and 0.84(95%CI: 0.80-0.88),respectively,significantly outperforming other indicators. Subgroup analysis revealed that FT was negatively correlated with male AMR,but this association was modulated by age,race,smoking status and diabetes status(P_(interaction)＜0.05). Kaplan-Meier survival analysis showed that different levels of TT and FT(Q1-Q4)were significantly positively correlated with survival rate(P＜0.001),while different levels of SHBG were significantly negatively correlated with survival rate,with patients in the Q4 group having the highest risk of death(P＜0.001). Conclusion Based on US NHANES,studies have shown that the FT and SHBG are independent risk factors for male AMR,and FT demonstrates greater predictive value for male AMR than TT.

Addressing the challenge of traditional physical/semi physical simulation methods being difficult to achieve full process and full element simulation of extravehicular activities,virtual reality technology is utilized to break through the limitations of physical environments and establish a virtual reality simulation system for extravehicular activities.Based on the application characteristics of space station extravehicular activity engineering,with the goal of improving system practicality and usability,integrating the visual immersion of virtual images,the ontology of real operation,and the consistency of virtual and real space perception,a three-dimensional scene simulation,multi-mode joystick interaction paradigm,continuous operation actions simulation of extravehicular operations,and interactive operation virtual/real space consistency method that were proposed and designed for the realistic visual perception and extravehicular operation.The system has been successfully applied to astronaut training,program validation,joint exercise,and flight control support for sixteen extravehicular activities from SZ-12 to SZ-18.The results showed that the complete reproduction of the static/dynamic realistic comprehensive scene was achieved on the ground for the human-machine operation in the entire process of extravehicular activity,and the system is an essential and important means of ground simulation for extravehicular activity.

With the rapid advancements in pancreatic cancer diagnosis and treatment research,the Chinese Society of Clinical Oncology(CSCO)has released two editions of pancreatic cancer diagnosis and treatment guidelines in 2022 and 2024.The present article systematic-ally compares the differences between the two editions in terms of diagnostic stratification,treatment pathways,and supportive manage-ment.By integrating insights from cutting-edge international research,the scientific rationale and clinical value of the underlying guideline revisions are explored.Clinicians are encouraged to adopt the new guidelines to dynamically assess the biological characteristics and treat-ment tolerance of patients,thereby formulating personalized diagnosis and treatment plans that ultimately lead to the synergistic enhance-ment of both survival benefits and quality of life for patients.

Objective:To investigate immunotherapy effects and mechanism of BCG and recombinant BCG(rBCG)with c-di-AMP as adjuvant on melanoma in mice model.Methods:Melanoma mice model was established by B16F10 cell subcutaneous injec-tion in groin,and treated with 1×106 CFU of BCG and rBCG by adjacent injection of subcutaneous tumor for 3 times,respectively.Survival of melanotic mice,tumor growth and metastasis were observed.Tumor tissues of mice were isolated to prepare cell suspen-sion,and proportion of immune cells were detected by flow cytometry.Transcriptional levels of immune-related genes in tumor tissues were detected by qRT-PCR.Results:Both BCG and rBCG immunotherapy could significantly inhibit growth in melanoma mice and prolong survival time of mice.rBCG showed better inhibition on metastasis than BCG.Both strains significantly reduced proportion of M2-type macrophages and myeloid-derived suppressor cell associated with tumor growth and metastasis.Both two strains promoted infiltration of lymphocytes in tumor tissues,and rBCG significantly increased proportion of B cells in tumor.BCG immunotherapy upregulated transcription levels of metastasis-related cytokines,while rBCG therapy had no effects on transcriptions of these genes.Conclusion:Both BCG and rBCG have immunotherapeutic effects on melanotic mice,and rBCG with c-di-AMP as adjuvant shows better inhibition on tumor metastasis than BCG,which mechanism was related to regulation of immune response in tumor tissues.

Objective:To investigate immunotherapy effects and mechanism of BCG and recombinant BCG(rBCG)with c-di-AMP as adjuvant on melanoma in mice model.Methods:Melanoma mice model was established by B16F10 cell subcutaneous injec-tion in groin,and treated with 1×106 CFU of BCG and rBCG by adjacent injection of subcutaneous tumor for 3 times,respectively.Survival of melanotic mice,tumor growth and metastasis were observed.Tumor tissues of mice were isolated to prepare cell suspen-sion,and proportion of immune cells were detected by flow cytometry.Transcriptional levels of immune-related genes in tumor tissues were detected by qRT-PCR.Results:Both BCG and rBCG immunotherapy could significantly inhibit growth in melanoma mice and prolong survival time of mice.rBCG showed better inhibition on metastasis than BCG.Both strains significantly reduced proportion of M2-type macrophages and myeloid-derived suppressor cell associated with tumor growth and metastasis.Both two strains promoted infiltration of lymphocytes in tumor tissues,and rBCG significantly increased proportion of B cells in tumor.BCG immunotherapy upregulated transcription levels of metastasis-related cytokines,while rBCG therapy had no effects on transcriptions of these genes.Conclusion:Both BCG and rBCG have immunotherapeutic effects on melanotic mice,and rBCG with c-di-AMP as adjuvant shows better inhibition on tumor metastasis than BCG,which mechanism was related to regulation of immune response in tumor tissues.

With the rapid advancements in pancreatic cancer diagnosis and treatment research,the Chinese Society of Clinical Oncology(CSCO)has released two editions of pancreatic cancer diagnosis and treatment guidelines in 2022 and 2024.The present article systematic-ally compares the differences between the two editions in terms of diagnostic stratification,treatment pathways,and supportive manage-ment.By integrating insights from cutting-edge international research,the scientific rationale and clinical value of the underlying guideline revisions are explored.Clinicians are encouraged to adopt the new guidelines to dynamically assess the biological characteristics and treat-ment tolerance of patients,thereby formulating personalized diagnosis and treatment plans that ultimately lead to the synergistic enhance-ment of both survival benefits and quality of life for patients.

Objectives:To visualize and analyze the research on the application of 3D printing technology in the field of spinal surgery at home and abroad,construct visualization maps,and provide reference for future research by comparing the research hotspots at home and abroad.Methods:The China National Knowledge Infrastructure(CNKI)database was searched using the keywords of"3D printing"and"spine"for literature published in 2013-2023 in Chinese;The Web of Science Core Collection database was used as English database,literature published in 2013-2023 with topics including"3D printing"and"Spine"were searched with"TS=(3D printing)AND TS=(Spine)".A total of 256 Chinese literature and 250 English literature were included and imported into CiteSpace software after excluding the duplicate and low relevance articles.The annual publication quantity,authors,keywords,countries,institutions,keyword clustering,and keyword promi-nence in both Chinese and English literature were visualized and analyzed.Results:The annual publication numbers of domestic and foreign publications from 2013 to 2023 were similar.The top three authors pub-lished the most Chinese literature were Li Chao,Niu Guoqi,and Sun He;The top three authors published the most English literature were Clifton William,Damon Aaron,and Nottmeier Eric.In the visualization map of Chinese literature keywords,there were 215 nodes and 617 lines with a density of 0.0273;The most fre-quently appeared keywords were 3D printing(148 times,1.09),spinal surgery(47 times,0.26),and scoliosis(30 times,0.10).In the English literature keyword visualization graph,there were 282 nodes and 1359 lines with a density of 0.0367;The most frequently appeared keywords were 3D printing(116 times,0.07),surgery(54 times,0.12),and accurate(42 times,0.18).A total of 206 nodes and 100 lines with a density of 0.0047 ap-peared in the visualization graph of the institutions of CNKI database,and 216 nodes and 147 lines appeared in the visualization graph of the institutions of Web of Science with a density of 0.0063.China published the most articles,followed by the United States and Australia.The top three institutions published the most Chi-nese literature were Peking University Third Hospital,Yan'an University Affiliated Hospital,and Bengbu Med-ical College Second Affiliated Hospital.The top three institutions published the most literature abroad were Mayo Clin,Southern Med Univ,and Capital Med Univ.After clustering the keywords of Chinese and English literature,6 meaningful clusters were obtained respectively.The most prominent keywords in Chinese and Eng-lish literature were tissue engineering and patient specific,respectively.Conclusions:The hot topics of 3D printing technology in spinal surgery research vary in countries.The connections between foreign institutions are relatively dense,while those in China are relatively scattered.

BACKGROUND:Medial open wedge high tibial osteotomy is an effective procedure for preserving the knee joint in patients with medial compartmental osteoarthritis.Previous studies have demonstrated that the forgotten joint score provides a lower ceiling effect and consistency of medial open wedge high tibial osteotomy outcomes compared to traditional assessment tools. OBJECTIVE:To identify predictive factors associated with the occurrence of a forgotten joint after medial open wedge high tibial osteotomy. METHODS:117 patients with medial open wedge high tibial osteotomy who were treated at First Affiliated Hospital of Guangzhou University of Chinese Medicine were selected,including 35 males and 82 females,with an average age of 61 years.They were followed up for at least 2 years.Patients were divided into a forgotten joint group(n=28)and a non-forgotten joint group(n=89)by evaluating whether they achieved forgotten joint after surgery.Univariate and multivariate logistic regression analyses were performed with preoperative patient characteristics and surgery-related factors as potential predictors. RESULTS AND CONCLUSION:(1)There were significant differences in the proximal medial tibial angle between the two groups before surgery(P<0.05).There were significant differences in the forgotten joint score,Knee Injury and Osteoarthritis Outcome Score,knee society knee score,function score,and patients joint perception between the two groups after surgery(P<0.05).There was a significant difference between the hip-knee-ankle angle and the medial proximal tibial angle after operation(P<0.05).(2)Univariate Logistic regression analysis showed that the medial proximal tibial angle had a significant influence on the forgotten joint before operation[OR=0.755,95%CI(0.635-0.897),P<0.001].There were significant effects on the forgotten joint of hip-knee-ankle angle and medial proximal tibial angle[OR=1.546,95%CI(1.242-1.924),P<0.001;OR=0.815,95%CI(0.713-0.931),P=0.003].(3)Multivariate logistic regression analysis showed that preoperative K-L grade 1 was a favorable factor for obtaining forgotten joints.Preoperative medial proximal tibial angle and postoperative hip-knee-ankle angle were independent predictors of forgetting joints,and they had a curvilinear relationship with the probability of achieving forgetting joints.When preoperative medial proximal tibial angle increased by 1°,the probability of achieving a forgotten joint decreased by 27.7%[OR=0.723,95%CI(0.593-0.882),P<0.001].Conversely,when postoperative hip-knee-ankle angle increased by 1°,the probability of achieving a forgotten joint increased by 46.4%[OR=1.464,95%CI(1.153-1.860),P=0.002].(4)The results showed that patients with preoperative knee osteoarthritis K-L grade 1,small medial proximal tibial angle(<85.5°),and large postoperative hip-knee-ankle angle(>176.0°)were predictors of forgotten joint.

Background/Aims: We aimed to study the effects of sedation on endoscopic ultrasound–guided tissue acquisition. Methods: We conducted a retrospective study evaluating the role of sedation in endoscopic ultrasound–guided tissue acquisition by comparing two groups: anesthesia care provider (ACP) sedation and endoscopist-directed conscious sedation (CS). Results: Technical success was achieved in 219/233 (94.0%) in the ACP group and 114/136 (83.8%) in the CS group (p=0.0086). In multivariate analysis, the difference in technical success between the two groups was not significant (adjusted odds ratio [aOR], 0.5; 95% confidence interval [CI], 0.234–1.069; p=0.0738). A successful diagnostic yield was present in 146/196 (74.5%) in the ACP group and 66/106 (62.3%) in the CS group, respectively (p=0.0274). In multivariate analysis, the difference in diagnostic yield between the two groups was not significant (aOR, 0.643; 95% CI, 0.356–1.159; p=0.142). A total of 33 adverse events (AEs) were observed. The incidence of AEs was significantly lower in the CS group (5/33 CS vs. 28/33 ACP; OR, 0.281; 95% CI, 0.095–0.833; p=0.022). Conclusions CS provided equivalent technical success and diagnostic yield for malignancy in endoscopic ultrasound–guided tissue acquisition. Increased AEs were associated with anesthesia for the endoscopic ultrasound–guided tissue acquisition.