BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

Steroid-associated osteonecrosis of the femoral head (SANFH) is a progressive osteoarticular disorder associated with prolonged or high-dose glucocorticoid exposure. Its development involves local ischemia, oxidative stress, dysregulated bone metabolism, and disruption of the osteoimmune microenvironment. Macrophages exhibit marked phenotypic plasticity, and their polarization is essential for maintaining the dynamic balance among inflammation, angiogenesis, and bone remodeling. Persistent glucocorticoid stimulation, hypoxia, excessive reactive oxygen species, and damage-associated signals released from necrotic tissues can shift macrophages toward a pro-inflammatory phenotype. Classically activated macrophages (M1 macrophages) predominantly mediate inflammatory responses. By releasing tumor necrosis factor-α, interleukin-1β, interleukin-6, and other mediators, promoting osteoclast activation, suppressing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and impairing vascular endothelial function, M1 macrophages accelerate trabecular destruction and expansion of the necrotic lesion. In contrast, alternatively activated macrophages (M2 macrophages) contribute to inflammation resolution, neovascularization, osteogenic repair, and tissue remodeling, thereby supporting regeneration within the necrotic region. Macrophage-derived exosomes further influence disease progression through intercellular communication. Exosomes from different macrophage phenotypes can differentially regulate adipogenic differentiation, neutrophil extracellular trap formation, and endothelial phenotypic transition, thereby affecting the repair capacity of the necrotic area. These findings indicate that macrophage polarization shapes the local microenvironment not only through soluble mediators but also through vesicle-mediated communication with BMSCs, neutrophils, endothelial cells, and other cell populations. At the molecular level, the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3) inflammasome, nuclear factor kappa B (NF‑κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathways jointly regulate macrophage polarization and its downstream osteoimmune effects. Dysregulation of these pathways may sustain inflammatory activation, aggravate oxidative and vascular injury, inhibit osteogenesis, and impair tissue repair. NLRP3 inflammasome activation links danger signals and oxidative stress to inflammatory cytokine maturation and pyroptotic injury; NF-κB signaling promotes pro-inflammatory gene transcription and M1 polarization; JAK/STAT signaling participates in the balance between inflammatory and reparative macrophage programs; and PI3K/Akt/mTOR signaling regulates cellular metabolism, survival, autophagy, and regeneration. Notably, the biological effects of PI3K/Akt/mTOR signaling are cell-type dependent, and Akt-mediated repair signaling should be distinguished from mTOR-related autophagy regulation. The pathological significance of macrophage polarization in SANFH is not determined simply by an increase or decrease in a single phenotype. Rather, disease progression appears to result from an imbalance between persistent pro-inflammatory activity and insufficient reparative responses at different stages of the disease. Such an imbalance disrupts the coordinated coupling of inflammation resolution, vascular regeneration, and bone remodeling, ultimately contributing to structural deterioration of the femoral head. This review summarizes the pathological roles, signaling regulation, and exosome-mediated intercellular communication associated with macrophage polarization imbalance in SANFH. A more precise understanding of these mechanisms may clarify the osteoimmune basis of SANFH and support the development of macrophage-targeted interventions. However, most available evidence is derived from cellular and animal studies, and the temporal evolution of macrophage phenotypes in patients remains insufficiently characterized. Therapeutic strategies should therefore move beyond the simple suppression of M1 macrophages or enhancement of M2 macrophages and instead aim to restore a stage-appropriate balance between inflammatory control and tissue repair while promoting angiogenesis and bone reconstruction.

ObjectiveOxygen partial pressure (pO₂) is a critical indicator of the tumor microenvironment and plays an essential role in regulating tumor progression and therapeutic response, particularly for oxygen-dependent treatments such as photodynamic therapy (PDT). Although photoacoustic imaging (PAI) has shown great potential for functional and molecular imaging, conventional oxygenation imaging approaches based on hemoglobin absorption mainly provide relative oxygen saturation information and cannot directly quantify tissue oxygen partial pressure. Therefore, this study aimed to develop a fast laser sequence-based pump-probe photoacoustic tomography (PP-PAT) system for quantitative, non-invasive, and dynamic monitoring of oxygen partial pressure in tumor tissues. MethodsThe proposed PP-PAT system was developed based on the oxygen-sensitive triplet-state lifetime characteristics of methylene blue (MB). Upon optical excitation, MB molecules undergo transitions from the ground state to an excited state and subsequently form metastable triplet states through intersystem crossing. The lifetime of the triplet state is strongly affected by surrounding oxygen concentration due to dynamic oxygen quenching, providing a direct correlation between triplet-state kinetics and local oxygen partial pressure. A dual-wavelength pump-probe excitation scheme was implemented to selectively interrogate MB triplet-state dynamics. The pump pulse was used to initiate the triplet-state population, while the delayed probe pulse was applied to detect the transient triplet-state response. By optimizing the temporal interval between the pump and probe pulses, transient triplet-state differential (TTD) signals were extracted to enhance the specificity of oxygen-dependent molecular information and suppress background interference from conventional photoacoustic signals. The performance of the PP-PAT system was systematically evaluated through phantom and in vivo experiments. First, a single-tube phantom containing MB solution was used to investigate signal stability, reproducibility, and the influence of signal averaging on imaging quality. Subsequently, a dual-tube phantom model was established to simulate oxygen consumption during PDT, where one MB-containing tube was exposed to laser irradiation and the other served as a control. Finally, in vivo experiments were performed using a subcutaneous tumor model in nude mice. MB was locally injected into the tumor region before imaging to evaluate the feasibility of tumor oxygen partial pressure mapping using the proposed PP-PAT system. ResultsPhantom experiments demonstrated that the extracted TTD signals exhibited high stability and effectively reflected MB triplet-state dynamics while reducing non-specific background contributions. Signal averaging significantly improved the signal-to-noise ratio, and 50 repeated acquisitions provided an optimal compromise between image quality and acquisition efficiency. In the dual-tube phantom experiments, continuous PDT irradiation induced progressive oxygen depletion in the treated sample. The corresponding TTD decay rate gradually decreased, accompanied by an increase in the calculated triplet-state lifetime, indicating reduced oxygen quenching and decreased oxygen partial pressure. In contrast, the control sample showed relatively stable TTD kinetics and oxygenation levels during the same period. These results demonstrated that PP-PAT could quantitatively characterize oxygen consumption dynamics associated with photochemical reactions. In vivo experiments further demonstrated the capability of PP-PAT for spatially resolved oxygen partial pressure imaging in MB-injected tumor tissues. The reconstructed pO₂ maps revealed heterogeneous oxygen distributions within tumors, showing relatively hypoxic regions in the tumor core and higher oxygenation levels near the tumor boundary. This spatial oxygen distribution pattern was consistent with the typical physiological characteristics of solid tumors, where abnormal vascular structures and limited oxygen diffusion result in intratumoral oxygen gradients. ConclusionThis study presents a fast laser sequence-based PP-PAT system capable of quantitative and non-invasive imaging of tissue oxygen partial pressure. By utilizing the oxygen-dependent triplet-state lifetime of MB and extracting TTD signals, the proposed method provides molecularly specific information related to oxygen dynamics beyond conventional photoacoustic oxygenation imaging. The system enables dynamic monitoring of oxygen consumption during PDT and reveals spatial oxygen heterogeneity within tumors. This technique provides a promising imaging approach for tumor hypoxia characterization, evaluation of oxygen-dependent therapeutic responses, and precision-guided cancer treatment.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Objective By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.

Objective:To explore the influence of operation timing on the prognosis of hip fracture in patients who used direct oral anticoagulant (DOAC) before injury.Methods:A retrospective case-control study was conducted to analyze the clinical data of 90 patients who used DOAC before hip fracture and were admitted to Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine from January 2022 to August 2023. Among them, there were 53 males and 37 females, aged 65 to 89 years with a mean age of (76.24±6.92) years. Patients were divided into the early operation group ( n=45) and the delayed operation group ( n=45) according to the timing of operation. The early operation group underwent hip fracture surgery within 2 days after DOAC withdrawal, while the delayed operation group underwent hip fracture surgery more than 2 days after DOAC withdrawal. The two groups were compared and evaluated in terms of fracture site, surgical method, operation time, length of hospital stay, Harris hip score (HHS), intraoperative blood loss, blood transfusion rate, blood transfusion volume, hemoglobin (Hb) change rate, incidence of postoperative complications, intensive care unit (ICU) admission rate and duration, and mortality rate. The measurement data with normal distribution were expressed as mean ± standard deviation ( ± s), and intergroup comparison was performed using the t-test. The count data were expressed as cases and percentages, and intergroup comparison was conducted using the Chi-test or Fisher exact test probability method. Comparisons among multiple time points were analyzed by repeated measures analysis of variance. Results:There was no statistically significant differences were observed between the two groups in terms of fracture site and surgical method ( P>0.05). The ICU admission rate and length of hospital stay in the early operation group were lower than those in the delayed operation group, with statistically significant differences ( P<0.05). There were no statistically significant differences between the two groups in intraoperative blood loss, operation time, blood transfusion rate, blood transfusion volume, Hb change rate and other indicators ( P>0.05). The total incidence of postoperative complications in the early operation group was lower than that in the delayed operation group [15.6% (7/45) vs 53.3% (24/45)], with statistically significant difference ( P<0.05). The HHS score of the early operation group at 1 month after operation was significantly higher than that of the delayed operation group, with statistically significant difference ( F=7.75, P<0.05). At 1 and 12 months after operation, there were no statistically significant differences in the mortality between the two groups of patients who used DOAC before hip fracture [0 (0/45) vs 2.2% (1/45); 4.4% (2/45) vs 6.7% (3/45); P>0.05]. Conclusion:For patients who used DOAC before injury, hip fracture surgery within 2 days after DOAC was stopped after admission can help to reduce the ICU admission rate, shorten the length of stay, reduce the risk of postoperative complications, and promote the early recovery of hip joint function, without affecting the amount of blood loss, blood transfusion rate and blood transfusion.

Gastrointestinal stromal tumor(GIST)is the most prevalent mesenchymal tumor of the gastrointestinal tract,with imatinib serving as the first-line drug for metastatic GIST due to its good clinical efficacy.However,the majority of patients exhibit tumor progression within several years of drug therapy,primarily due to the high rate of drug resistance,which significantly impedes drug therapeutic outcome and patient prognosis.Traditional approaches to counteract resistance,including dosage increase and subsequent line therapy yielded suboptimal results.As a research hotspot,intestinal flora has been proven to be closely related to drug resistance of various tumors.In recent years,it has been observed that specific intestinal flora could serve as biomarkers for early GIST patient screening or as potential drug targets,and modulating the intestinal flora through interventions may delay or even reverse the progression of imatinib secondary drug resistance in GIST.This review delineates the drug resistance of GIST,correlations between intestinal flora and drug resistance of tumors,as well as the relationship between intestinal flora and drug resistance of GIST,aiming to provide novel perspectives and methodologies for clinical application.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.