Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

BACKGROUND:The stemness index may be associated with the prognosis and immune infiltration of sarcoma,but the specific regulatory mechanism and characteristic genes have yet to be fully elucidated. OBJECTIVE:To investigate the correlation between stem cells and prognosis as well as immune infiltration in sarcoma employing the gene stemness index model and to identify the ferroptosis signature genes associated with sarcoma stem cells. METHODS:The sarcoma RNA sequencing data and related clinical information were obtained from the Cancer Genome Atlas(TCGA).The sarcoma RNA sequencing data were grouped using the sarcoma stemness index.Survival data were used to analyze prognosis between groups.Differentially expressed genes were obtained for pathway enrichment and immune infiltration analysis.Ferroptosis-related differential genes were used to construct a protein interaction network and analyze prognostic correlation.Rhabdomyosarcoma cell lines were cultured and divided into adherent cell group and stem cell group.The adherent cell group received no intervention,while the stem cell group was treated with serum-free culture to enrich stem cells in rhabdomyosarcoma cells.qRT-PCR was used to evaluate stemness markers,ferroptosis-related genes,and mRNA expression of ferroptosis-related markers in the cells. RESULTS AND CONCLUSION:(1)Patients were divided into high and low stemness index groups based on the median stemness index.The progression-free survival of patients in the high stemness index group was lower than that in the low stemness index group by disease risk prediction,suggesting poor prognosis.(2)According to GO and KEGG analysis,the groups with high and low stemness indices differed from one another.There were differences in immune infiltration between the high and low stemness index groups.Nine of the 23 ferroptosis-related genes in the differential genes have the potential to establish a highly correlated network of protein interactions.Patients with high expression of IDO1,IFNG,and AQP5 have a better prognosis,while those with high expression of CA9 have a poor prognosis.(3)The qRT-PCR results demonstrated a significant upregulation of stem cell-related markers NANOG,SOX2,and OCT4 mRNA expressions in the stem cell group compared to the adherent cell group(P<0.05).Compared to the adherent cell group,the stem cell group exhibited decreased mRNA expression level of ferroptosis-related marker SLC7A11(P<0.05)while showing increased levels of ACSL4,GPX4,FTH1,and COX2(P<0.05).Compared to the adherent cell group,the stem cell group displayed decreased mRNA expression level of differentially expressed gene CA9 alongside elevated levels of IDO1,IFNG,and AQP5(P<0.05).Stem cells were strongly associated with sarcoma survival and ferroptosis by bioinformatics analysis and experimental verification.Sarcoma stem cells have aberrant expression of CA9,IDO1,IFNG,and AQP5,which may serve as new targets for sarcoma therapy as well as diagnostic indicators.

The CyberKnife, an acronym for the stereotactic radiosurgery platform, represents an image-guided stereotactic radiotherapy technique. This technology precisely delivers ionizing radiation to tissues, effectively damaging tumor cells, and is suitable for radiotherapy of both intracranial and extracranial tumors. This article reports the first performance of CyberKnife by radiotherapy at Peking Union Medical College Hospital, including a patient with uncontrolled pituitary adenoma after surgery and radiotherapy, and another patient with vertebral metastasis following targeted therapy for lung adenocarcinoma. The application of CyberKnife technology in radiotherapy has achieved highly accurate dose delivery, enabling targeted irradiation of tumor lesions while minimizing damage to surrounding normal tissues, thereby yielding relatively ideal clinical outcomes.

Objective:To investigate the clinical efficacy of 3D laparoscopic radical gastrec-tomy of gastric cancer.Methods:The prospective randomized controlled study was conducted. The clinical data of 90 patients undergoing total laparoscopic radical gastrectomy of gastric cancer in Zhangzhou Affiliated Hospital of Fujian Medical University from January to December 2022 were selected. Patients were randomly divided into the 3D laparoscopic group and the 2D laparoscopic group by the method of random number table. Patients underwent 3D or 2D laparoscopic radical gastrectomy of gastric cancer. Observation indicators: (1) grouping of enrolled patients; (2) intra-operative and postoperative situations; (3) feelings of the major surgeon during the operation. Com-parison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups wsa conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the nonparametric test. Results:(1) Group of enrolled patients. A total of 90 patients eligible for total laparoscopic radical gastrectomy of gastric cancer were selected. There were 56 males and 34 females, aged (61±7)years. All 90 patients were randomly divided into the 3D laparoscopic group and the 2D laparoscopic group, with 45 cases in each group. There was no significant difference in gender, age, body mass index, hypertension, diabetes mellitus, history of abdominal surgery, surgical method, tumor site and TNM staging between the two groups ( P>0.05), indicating comparability. (2) Intraoperative and postoperative situations. The operation time of the 3D laparoscopic group and the 2D laparoscopic group were (196±12)minutes and (204±14)minutes, respectively. The digestive tract reconstruction time of the 3D laparoscopic group and the 2D laparoscopic group were (81±8)minutes and (87±12)minutes, respectively. There were significant differences in operation time and digestive tract reconstruction time between the two groups ( t=-2.85, -2.43, P<0.05). After surgery, 3 cases of the 3D laparoscopic group experienced complications (1 case of abdominal infection, 2 cases of intestinal obstruction), and 8 cases of the 2D laparoscopic group experienced complications (2 cases of anastomotic leakage, 2 cases of abdominal infection, 4 cases of intestinal obstruction). There was no significant difference in postoperative complications between the two groups ( χ2=2.59, P>0.05). (3) Feelings of the major surgeon during the operation. After surgery, the major surgeon completed a questionnaire survey. The score of image quality perception of the 3D laparoscopic group and the 2D laparoscopic group were 4.73±0.08 and 4.46±0.09, respectively. The score of hand-eye coordination experience of the 3D laparoscopic group and the 2D laparoscopic group were 4.60±0.09 and 4.55±0.08, respectively. The score of operation comfort of the 3D laparoscopic group and the 2D laparoscopic group were 4.81±0.05 and 4.62±0.08, respectively. The score of eye comfort of the 3D laparoscopic group and the 2D laparoscopic group 4.49±0.07 and 4.68±0.07, respectively. There were significant differences in the above indicators between the two groups ( t=15.04, 2.57, 13.51, -12.88, P<0.05). Conclusions:Compared with 2D laparoscopy, 3D laparoscopic radical gastrec-tomy of gastric cancer has shorter operation time and digestive tract reconstruction time, does not increase postoperative complications, and has better feelings of the major surgeon in image quality perception, hand-eye coordination experience and operation comfort.

Objective To investigate stress distributions of the knee joint at 0 and 15th day after anterior cruciate ligament reconstruction(ACLR)under a compressive force through the axis of the femoral shaft onto the proximal femur.Methods A three-dimensional(3D)finite element model of the human knee joint incorporating viscoelastic material properties was developed.The one-dimensional(1D)Prony series viscoelastic constitutive model parameters for articular cartilage,menisci,ligaments,and anterior cruciate ligament(ACL)grafts were determined by fitting experimental creep curves.The viscoelastic parameters of ACL grafts at 15th day after ACLR surgery were extrapolated.Finite element simulations were then performed to analyze the von Mises stress distributions in knee ligaments,ACL grafts,articular cartilage,and menisci under 1.5 kN vertical downward compressive load applied to the femur,with loading durations of 1 second and 600 seconds.Results At 15th day after ACLR surgery,the initial relaxation modulus and equilibrium modulus of human ACL grafts remained elevated compared to native ACL tissues,resulting in a significantly higher stress concentration within the grafts relative to healthy ACL.Despite the compromised mechanical properties of the grafts after ACLR surgery,the vertical downward compressive force applied to the femur under both short-term(1s)and prolonged(600 s)loading durations,exhibited a minimal biomechanical impact on articular cartilage and meniscal structures.Conclusions Following ACLR,vertical compressive loads during weight-bearing rehabilitation exercises such as standing demonstrate minimal impact on articular cartilage and meniscus,while promoting fibrous regeneration of the graft.This renders such exercises a prudent early-stage rehabilitation strategy.Graft preparation requires balanced consideration of elastic and viscous properties,with grafts exhibiting higher relaxation modulus and viscosity coefficient than healthy ACL proving more effective in maintaining early postoperative knee stability.

High altitude heart disease(HAHD)is a chronic mountain sickness in which the body is exposed to high altitude(＞2 500 m)hypobaric hypoxia environment for a long time.HAHD has high morbidity and poor prognosis,and pulmonary hypertension is the main causative mechanism for its develop-ment.The phosphodiesterase-5 inhibitor sildenafil has become a hot drug for the treatment of pulmonary hypertension.This paper reviews the progress of HAHD and discusses the mechanism of action and effectiveness of sildenafil in the treatment of HAHD,with a view to providing a basis for the treatment of HAHD with sildenafil.

The immune microenvironment plays a pivotal role in maintaining ovarian homeostasis. Polycystic ovary syndrome (PCOS), a common endocrine and metabolic disorder, is closely associated with immune microenvironment imbalance. This review systematically describes the dysregulation of innate immune cells (e.g., macrophages, natural killer cells and dendritic cells) and adaptive immune cells (e.g., Th1, Th2, Treg and Th17) in PCOS, highlighting their impacts on ovarian function, insulin resistance, and hyperandrogenemia. These findings underscore the central role of immune microenvironment disturbances in PCOS pathogenesis. Additionally, the association between gut microbiota dysbiosis and PCOS is explored, emphasizing how gut microbiota influences metabolic byproducts and hormonal levels to contribute to PCOS development. Furthermore, therapeutic strategies targeting immune microenvironment imbalance such as modulating macrophage polarization, restoring Th1/Th2 and Th17/Treg balance, and ameliorating gut microbiota dysbiosis are discussed, offering novel insights for PCOS immunotherapy. In conclusion, this review comprehensively analyzes the pathogenesis of PCOS from the perspective of the immune microenvironment, aiming to provide a theoretical foundation and reference for future research and clinical practice.

Objective:To evaluate the clinical rehabilitation effect of external counterpulsation(ECP)on patients with coronary heart disease(CHD)by meta-analysis.Methods:We searched the databases of CNKI,WanFang,VIP,CBM,PubMed,Web of Science,Cochrane Library and Embase for randomized controlled trials(RCTs)and prospective cohort studies upon rehabilitative effect of ECP on CHD patients before May 2024.And meta-analysis was conducted to calculate the pooled MD and 95％CI using the random(P＜0.5 or I2≥50％)or fixed effect models(other situations).Results:13 eligible literatures were finally included in the meta-analysis.Compared with participants in control group,those in trial group had significant higher left ventricular ejection fraction(MD=4.15,95％CI 2.55～5.76,P＜0.001),stroke volume(MD=9.11,95％CI 7.59～10.64,P＜0.001),peak oxygen uptake(MD=5.42,95％CI 2.53～8.32,P＜0.001),6-min walking distance(MD=31.14,95％CI 24.89～37.40,P＜0.001),metabolic equiv-alent(MD=0.58,95％CI 0.45～0.71,P＜0.001),exercise duration time(SMD=0.77,95％CI 0.55～0.99,P＜0.001),oxygen pulse(MD=0.88,95％CI 0.68～1.09,P＜0.001),and significant lower left ventricular end-diastolic diameter(MD=-3.19,95％CI-5.20～-2.61,P＜0.001).Conclusion:This study showed that ECP could effectively improve heart function,exercise capacity and tolerance of CHD patients.

Objective:To analyze the association between moderate-to-vigorous-physical activity (MVPA) and obesity, poor sleep quality, as well as multimorbidity in 7- to 8-year-old children in Shanghai City.Methods:From September to November 2023, a cluster sampling method was used to select second-grade students from four primary schools in Jinshan District, Shanghai. Three-axis acceleration motion sensors (GT3X+, Acti-graph) were used to monitor daily physical activity for seven consecutive days. A multivariate logistic regression model was used to analyze the association between MVPA duration characteristics and obesity, poor sleep quality and multimorbidity in school-age children.Results:Of the 937 study participants, 512 (54.64%) were boys and 425 (45.36%) were girls. Among them, 89 (9.50%) were obese and 782 (83.46%) had poor sleep quality. A total of 77 cases (8.22%) were affected by obesity and poor sleep quality. The average daily MVPA time was (45.97±15.87) minutes, and the MVPA attainment rate was 17.18%. The multivariate logistic regression model analysis showed that, after adjusting for covariates, the daily average MVPA time was negatively associated with the risk of obesity ( OR=0.982, 95% CI: 0.968-0.997), as well as multimorbidity ( OR=0.981, 95% CI: 0.965-0.997). The risk of obesity, poor sleep quality and multimorbidity in <1 d was 2.228 ( OR=2.228, 95% CI: 1.398-3.549), 1.702 ( OR=1.702, 95% CI: 1.141-2.540) and 2.150 ( OR=2.150, 95% CI: 1.310-3.528) times higher than that in ≥1 d. Conclusion:Obesity, poor sleep quality and multimorbidity of school-age children are closely related to the level of moderate-to-vigorous physical activity.