Doxorubicin (DOX)-induced cardiotoxicity and sepsis-induced myocardial injury (SIMI) represent significant clinical challenges in patients undergoing chemotherapy, sharing a common pathological basis of oxidative stress and mitochondrial dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been shown to play a critical role in DOX-induced cardiotoxicity and lipopolysaccharide (LPS)-induced SIMI. This article systematically reviews the mechanisms underlying myocardial injury caused by DOX and sepsis, identifying ferroptosis as a central common pathway. DOX triggers a burst of reactive oxygen species within mitochondria and inhibits glutathione peroxidase 4 (GPX4) activity through redox cycling of its quinone group and high-affinity accumulation in mitochondrial cardiolipin. LPS, by activating pattern recognition receptors and related inflammatory signaling pathways, provokes a cytokine storm and mitochondrial dysfunction. Both can disrupt the core regulatory axis of cysteine-glutathione (GSH)-GPX4, synergistically promoting ferroptosis in cardiomyocytes. Moreover, epigenetic regulation plays a key role in DOX- and LPS-induced cardiomyocyte ferroptosis and may serve as a promising therapeutic target. A deeper understanding of the ferroptosis mechanism and its epigenetic regulatory network in the synergistic injury induced by DOX and sepsis is of great importance for developing novel strategies to mitigate chemotherapy-related cardiotoxicity and improve outcomes in cancer patients with concurrent infections.

To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine，the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13，2024，the 36^th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing，focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction （ED）. The conference brought together leading experts from traditional Chinese medicine，western medicine，and interdisciplinary fields，facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED，researching and developing new drugs of traditional Chinese medicine，and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs，it identified key directions for future scientific layout and scientific research tackling： （1） Standardization of syndrome differentiation system of traditional Chinese medicine for ED. （2） Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. （3） High-quality clinical research guided by evidence-based medicine. （4） In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. （5） Clinical translation and application promotion of new drugs of traditional Chinese medicine. （6） Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction，key focus areas，expected objectives，and clinical value were further refined，along with the establishment of a scientifically sound priority funding level evaluation system. Therefore，building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine，this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management，effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout， research and development decision-making in new drugs of traditional Chinese medicine，research topic planning，and clinical guideline formulation.

Objective: To analyze the developmental trajectories of clustered health risk behaviors and their association with self-esteem and lonelinesss among junior high school students, so as to provide a reference for formulating comprehensive prevention and control measures of health risk behaviors among adolescents. Methods: In October 2023, 1 165 first year junior high school students from two schools of Jishou City in Hunan Province were selected by convenient sampling method for three follow up surveys (T1:October 2023; T2:April 2024; T3:October 2024). The Adolescent Health Risk Behavior Questionnaire, Rosenberg Self esteem Scale and Loneliness Scale were used to assess health risk behaviors, self esteem and loneliness, respectively. Latent growth curve modeling and latent growth mixture modeling were applied to analyze the developmental trajectories of clustered health risk behaviors among junior high school students. Logistic regression was used to analyze the association of the developmental trajectories of clustered health risk behaviors with self esteem and loneliness among junior high school students. Results: The overall developmental trajectories among junior high school students showed a declining trend (intercept=0.15, slope=-1.65, both P <0.05), with three heterogeneous categories:low risk improvement group ( n =862, 74.0%), moderate risk stable group ( n =260, 22.3%), and high risk deterioration group ( n =43, 3.7%). After adjusting the status of the left behind individuals，using the low risk improvement group as the reference category in multinomial Logistic regression analysis, results indicated that higher loneliness scores among junior high school students increased the risks of belonging to the moderate risk stable group ( OR=1.02, 95%CI =1.00- 1.04 ) and the high risk deterioration group ( OR=1.04, 95%CI =1.00-1.08), while higher self esteem scores reduced the risks of belonging to the moderate risk stable group ( OR=0.93, 95%CI =0.91-0.96) and the high risk deterioration group ( OR=0.88, 95%CI =0.83-0.94) (all P <0.05). Conclusions The overall trend of clustered health risk behaviors among junior high school students gradually improves, and the self esteem and loneliness are significant correlative factors. Targeted intervention measures should be developed for the junior high school students, with a focus on enhancing their self esteem and alleviating loneliness.

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

ObjectiveTo evaluate the effect of Ningying Formula （宁瘿方） combined with low-dose antithyroid drugs （ATDs） on the relapse risk for patients with Graves' hyperthyroidism （GH） during the remission phase， and to analyze the related factors between GH relapse and thyrotropin receptor antibody （TRAb） negativity， so as to provide evidence for the standardized management of GH in remission stage. MethodsA single-center retrospective cohort study was conducted， including 269 GH patients in the remission stage. After propensity score matching （PSM）， 102 matched pairs （204 patients） were established. The control group received low-dose ATDs as maintenance therapy， while the exposure group received the core Ningying Formula in addition to low-dose ATDs. The primary outcome was the GH recurrence rate； the secondary outcome was the thyrotropin receptor antibody （TRAb） negativity rate （TRAb＜1.75 IU/L）. Safety outcomes included treatment-related adverse events. Differences between groups were assessed using Cox regression models and Kaplan-Meier curves， with sensitivity analysis performed using inverse probability of treatment weighting （IPTW）. ResultsThe median follow-up in the matched cohort was 28.07 months. Regarding the GH recurrence outcome， the recurrence rate in the exposure group （18/102， 17.6%） was significantly lower than that in the control group （31/102， 30.4%； χ²=4.539， P=0.033）； regarding the TRAb negativity outcome， the TRAb negativity rate in the exposure group （50/102， 49.0%） was significantly higher than that in the control group （23/102， 22.5%； χ²=15.551， P＜0.001）. Multivariate Cox regression analysis for recurrence showed that Ningying Formula treatment reduced the risk of recurrence ［HR=0.324， 95%CI（0.170， 0.617）， P＜0.001］. Male ［HR=2.209， 95%CI（1.079， 4.520）， P=0.030］， higher initial TRAb level ［per 1 IU/L increase： HR=1.033， 95%CI（1.003， 1.064）， P=0.032］， and larger thyroid volume ［per 1 ml increase： HR=1.045， 95%CI（1.003， 1.088）， P=0.035］ were identified as independent risk factors for recurrence； multivariate Cox regression analysis for TRAb negativity indicated that Ningying Formula treatment promoted TRAb negativity ［HR=1.826， 95%CI（1.091， 3.056）， P=0.022］， while a higher initial TRAb level was associated with a lower probability of negativity ［HR=0.974， 95%CI（0.950， 0.998）， P=0.032］. Survival analysis showed significant differences in relapse rate between groups （Log-Rank P=0.003） and in TRAb outcomes （Log-Rank P=0.034）. The incidence of treatment-related adverse events was similar between groups （P=0.757）. The IPTW sensitivity analysis was consistent with the primary analysis， indicating robust results. ConclusionThe Ningying Formula combined with low-dose ATDs can significantly reduce the risk of recurrence and can improve the TRAb negativity rate in GH patients during the remission stage， without increasing common adverse events， making it an optional strategy for reducing relapse risk during remission. Male gender， higher baseline TRAb level， and larger thyroid volume indicate a higher risk of recurrence， warranting focused follow-up and stratified management.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

Objective:To explore the diagnostic value of transcranial magnetic stimulation (TMS), transsacral magnetic root stimulation combined with sacral reflexes, external anal sphincter electromyography and pudendal nerve somatosensory evoked potentials in the assessment of neurogenic lower urinary tract dysfunction (NLUTD).Methods:Twenty-one NLUTD patients (1 with a supra-pontine lesion, 5 with a spinal cord injury, 5 with a cauda equina injury, and 10 with pelvic floor disorders) were enrolled. Needle electromyography (EMG) was used to record TMS-induced and transsacral magnetic stimulation-induced motor evoked potentials (tc-MEPs and ts-MEPs, respectively) related to the external anal sphincter (EAS). The dorsal nerve of the penis or clitoris was stimulated electrically to record the latency of the sacral reflex related to the EAS. Central motor conduction time (CMCT) and the tc/ts-MEP latency ratio were calculated to distinguish central from peripheral lesions.Results:In the one patient with a supra-pontine lesion, although the tc-MEP and ts-MEP latencies were within normal limits, the CMCT was prolonged (28.2ms) and the tc/ts-MEP ratio was large (7.4). Among the five patients with a spinal cord injury, one exhibited prolonged tc-MEP latency (50.6ms) and CMCT (47.8ms), along with a large tc/ts-MEP ratio (18.1). In the five patients with cauda equina injury and the ten with NLUTD secondary to pelvic floor disorders, CMCT was within the normal range [averaging (22.9±4.9ms) and (24.2±3.5ms), respectively], but the ts-MEP latency was prolonged [(7.1±2.1ms) and (8.6±3.7ms), respectively], and the tc/ts-MEP ratio was small [(4.4±0.9) and (4.3±1.5), respectively]. The tc/ts-MEP ratio demonstrated the best rate of abnormality detection (93.8%), with an area under the curve of 0.99, indicating good sensitivity.Conclusions:The tc/ts-MEP ratio can be useful for distinguishing central and peripheral lesions. A markedly increased tc/ts-MEP ratio may suggest central nervous system injury, whereas a decreased ratio may indicate peripheral nervous system injury.

Non-inferiority clinical trials are a research paradigm that employs randomized controlled methods to evaluate whether the treatment effect of the experimental group is not inferior to that of the active control group within a predefined acceptable margin. This article systematically summarizes the applicable conditions, key design elements, and statistical analysis methods for non-inferiority trials. By integrating representative case studies in the field of oncology, it elucidates the unique value of non-inferiority designs in balancing benefits and risks and in optimizing therapeutic decisions. Through reviewing theoretical frameworks and addressing common misconceptions in methodological practices, this study aims to provide clear guidance for the standardized design and scientific interpretation of non-inferiority trials, thereby promoting their high-quality application in clinical research.

Objective:To analyze the incidence of adverse treatment outcome of rifampicin-resistant tuberculosis (RR-TB) patients and influencing factors in 9 provinces in China.Methods:The information about the basic characteristics, diagnosis and treatment of RR-TB patients registered from January 1, 2017 to December 31, 2021 in 9 provinces (Beijing, Jilin, Shanghai, Jiangsu, Zhejiang, Hubei, Henan, Yunnan and Guizhou) were collected from the tuberculosis information management sub-system of China Disease Control and Prevention Information System for a descriptive analysis, and the influencing factors of adverse treatment outcome were identified by binary logistic regression analysis.Results:In 18 204 RR-TB patients in this study a total of 6 852 had adverse treatment outcomes (37.64%). Treatment failure occurred in 1 031 patients, 1 272 patients died, 2 284 patients were lost to follow-up, and 2 265 patients were not evaluated. The results of multivariate logistic regression analysis showed that being man (a OR=1.54, 95% CI: 1.43-1.66), age ≥65 years (a OR=2.42, 95% CI: 2.20-2.67), being from other ethnic groups (a OR=1.18, 95% CI: 1.03-1.35), being farmer (a OR=1.22, 95% CI: 1.13-1.32), being retired with honours or being retired (a OR=1.16, 95% CI: 1.00-1.35) and being floating population (a OR=1.23, 95% CI: 1.13-1.34), re-treatment (a OR=1.33, 95% CI: 1.24-1.42), long-term treatment therapy (a OR=3.26, 95% CI: 2.52-4.23), living in central provinces (a OR=2.76, 95% CI: 2.55-2.99), living in western provinces (a OR=2.31, 95% CI: 2.08-2.57) were the influencing factors for adverse treatment outcome of RR-TB. Conclusions:The incidence of adverse outcomes in RR-TB patients in 9 provinces in China was higher from 2017 to 2021. There were many influencing factors associated with adverse treatment outcome in RR-TB patients, especially the area specific factors. The national tuberculosis control program should strengthen the follow-up and treatment management of RR-TB in men, the elderly, floating population, people in central and western provinces and other key groups, actively promote the short-term treatment program and improve the allocation of medical resources to reduce the influencing for adverse treatment outcomes in RR-TB patient.