Posterior rib fractures represent severe thoracic trauma and are associated with a higher risk of complications due to their proximity to vital intrathoracic structures, including the intercostal vessels and lungs. Surgical stabilization of rib fractures (SSRF) has emerged as an operative strategy to restore chest wall stability, improve respiratory mechanics, and reduce pain. However, evidence specifically addressing posterior rib fractures remains limited, and current understanding is largely extrapolated from studies involving general rib fracture populations. This literature review evaluates the principles, operative techniques, effectiveness, and limitations of SSRF in posterior rib fractures, with an emphasis on surgical timing, technical challenges, and postoperative rehabilitation. Current evidence suggests that SSRF may reduce respiratory complications and improve outcomes in selected patients. Studies report reductions in pneumonia incidence and up to a 95% decrease in tracheostomy requirements in patients with flail chest. Surgical timing also influences outcomes, with pneumonia reported in 18% of patients undergoing SSRF within 72 h compared with 58% in those receiving delayed stabilization. SSRF may provide clinical benefits in appropriately selected patients with rib fractures. However, evidence specifically addressing posterior rib fractures remains limited, and further high-quality studies are required to clarify optimal indications and surgical strategies.
抗栓治疗是冠心病综合管理的核心环节，直接决定患者缺血与出血风险的平衡及远期临床预后。近年来，随着新药研发、治疗策略迭代与风险评估技术进步，冠心病抗栓治疗正从传统标准化方案转向精准化、个体化模式。该文围绕新型抗栓药物研发进展、抗栓治疗策略革新、缺血与出血风险预测模型构建等方面，系统梳理该领域现状，剖析关键挑战，并对未来发展方向进行述评，为临床实践与科学研究提供参考。.
This study presents the fabrication and magnetically tunable photoresponse behavior of p⁺-Si/CZFO/AZO and p⁺-Si/CZFDO/AZO trilayer heterostructures prepared by radio frequency magnetron sputtering. The structural, morphological, optical, and magnetic characteristics of Co0.7Zn0.3Fe2O4 (CZFO) and Dy3+ doped Co0.7Zn0.3Fe2O4 (CZFDO) spinel ferrite thin films were studied thoroughly. Photoresponse characteristics of the fabricated trilayer devices under broadband illumination (39.6 [Formula: see text] [Formula: see text], 300-1100 [Formula: see text]) demonstrate that the CZFDO based photodetector exhibits nearly threefold higher photocurrent density ([Formula: see text]), faster rise ([Formula: see text]) and decay times ([Formula: see text]), and greater responsivity [Formula: see text] and specific detectivity ([Formula: see text]) compared to the CZFO based device at + 5 [Formula: see text] bias. The application of an external magnetic field (0 to 3000 [Formula: see text]) further enhances the photocurrent by promoting spin aligned carrier transport and reducing recombination losses, confirming magneto-photoelectric coupling. The values of [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] also change significantly with the application of a magnetic field for both devices. The best obtained values of rise and fall times are [Formula: see text] and [Formula: see text] for the CZFDO based device at + 5 [Formula: see text] bias and 3000 Oe field. Interestingly, both devices retain partial photocurrent even after removing the field. These heterostructure devices with high photocurrent to dark current ratios and fast switching action can play the role of magnetically tunable broadband photodetectors, suitable for potential applications in magneto-optoelectronic sensors and spintronic devices.
To review recent research progress on nerve transfer for the reconstruction of upper limb function following peripheral nerve injury and central nervous system injury. A retrospective analysis of recent domestic and international literature on nerve transfer was conducted. The evolution of nerve transfer surgery from its application in peripheral nerve injuries to its extension to central nervous system injuries was described. The current therapeutic status of nerve transfer in upper limb hemiplegia resulting from spinal cord injury and brain injury was discussed, and the central role of central nervous system plasticity in postoperative functional recovery was analyzed. Nerve transfer is a crucial technique for upper limb function reconstruction, initially used to treat peripheral nerve injuries such as brachial plexus injuries. In recent years, this technique has gradually expanded into the field of central nervous system injuries. In cervical spinal cord injuries, various nerve transfer procedures can restore elbow flexion, wrist extension, and hand grasping functions, with efficacy correlated with the activation of plasticity in the spinal cord distal to the injury site. In cases of upper limb hemiplegia following brain injury, contralateral C 7 nerve transfer is the primary procedure, which can significantly reduce muscle tone and improve partial motor function; however, its ability to enhance fine motor skills and key muscle strength remains limited, and challenges such as maladaptive plasticity and co-activatory patterns persist. Mechanisms of central plasticity involve interhemispheric reorganization, activation of cortico-red nucleus-spinal pathways, and the remodeling of sensorimotor networks. The expansion of nerve transfer techniques from "peripheral repair" to "induction of central plasticity" offers a new strategy for treating central upper limb paralysis. However, current applications in brain injury are limited by a lack of surgical diversity and restricted central plasticity. Future efforts should integrate cell/gene therapy, electrical stimulation, novel transfer techniques, and systematic rehabilitation training to enhance neural regeneration and central plasticity, thereby further improving therapeutic outcomes. 综述神经移位术重建周围神经损伤及中枢神经系统损伤患者上肢功能的研究进展。. 回顾分析近年国内外有关神经移位术文献，阐述神经移位术从周围神经损伤拓展至中枢神经系统损伤的演变历程，重点探讨其在脊髓损伤和脑损伤偏瘫上肢中的治疗现状，并分析中枢可塑性在术后功能恢复中的核心作用。. 神经移位术是上肢功能重建的重要技术，最初用于臂丛损伤等周围神经损伤治疗，近年来已逐步拓展至中枢神经系统损伤领域。在颈髓损伤中，多种神经移位术可重建屈肘、伸腕及手部抓握功能，其疗效与激活损伤远端脊髓可塑性相关；在脑损伤偏瘫上肢中，以健侧C 7神经移位术为主，可显著降低肌张力、改善部分运动功能，但其对手部精细动作及关键肌力的提升仍有限，且存在适应不良性重塑、联合运动模式等挑战。中枢可塑性机制涉及半球间重组、皮质-红核-脊髓通路激活及感觉运动网络重塑等。. 神经移位术从“外周修复”向“诱导中枢重塑”的拓展为中枢性上肢瘫提供了新策略，但当前在脑损伤中的应用术式单一、中枢重塑受限。未来需结合细胞/基因治疗、电刺激、新型移位术式及系统性康复训练，以增强神经再生与中枢可塑性，进一步提升疗效。.
The synthesis of psychopharmaceuticals in the twentieth century marked the beginning of modern psychopharmacology, replacing earlier first-line psychiatric management that relied on psychosurgery, physical restraint, or administering narcotics and sedatives, e.g., morphine and chloral, which suppressed psychotic outbreaks temporarily without addressing the origin. Chlorpromazine's effective management of psychosis in the early 1950s opened the door for non-surgical therapies, making psychopharmaceuticals the current first-line treatment. While modern psychopharmacology began in the 1950s, the history of psychopharmacology may extend back many years. The concept of treating patients by understanding the cause and healing the mind was also evident during the Islamic Golden Age (ninth to thirteenth century CE). One of the physicians in the field was Rhazes (865-925 CE), also known as Abu Bakr Muhammad ibn Zakariyya Al-Razi. Rhazes' contributions to both psychiatry and pharmacology make his work a subject for examining the roots of psychopharmacology. This study aims to explore Rhazes' pharmacological approaches for patients with mental illnesses, focusing on the conditions under which he prescribed herbs for neurological, psychological, and psychiatric issues. An analytical approach has been utilized to systematically extract data from Al-Hawi and Liber Almansoris concerning neurological, psychological, psychiatric, and behavioral conditions. For the next phase, another table was created to list each condition alongside its treatment and psychopharmacological classification based on the works of Rhazes. Based on the collected information from Rhazes' Al-Hawi and Liber Almansoris, each of the mentioned neurological, psychological, psychiatric, and behavioral conditions was categorized. Rhazes distinguished between different psychological conditions and avoided using a universal prescription. He also differentiated between conditions that necessitated pharmacological interventions and those that could be effectively addressed through lifestyle modifications, nutritional adjustments, or manual therapy (hands-on therapy techniques like massage for managing musculoskeletal problems). The current historical study indicates that the roots of psychopharmacology can be traced back to the ninth century, during which the physician Rhazes documented various psychological and psychiatric diseases in his works Al-Hawi and Liber Almansoris, along with their natural pharmacological treatments. This historical perspective can enhance our understanding of psychopharmacology and provide new insights for expanding the range of psychopharmacological agents. Clinical trial number: Not applicable.
Objective: To evaluate the efficacy and safety of ticagrelor versus clopidogrel in real-world patients with acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRF-less) following percutaneous coronary intervention (PCI). Methods: This retrospective cohort study was based on a single-center, prospective PCI registry. SMuRF-less ACS patients (defined as the concurrent absence of hypertension, diabetes mellitus, hyperlipidemia, and current smoking at admission) who underwent PCI at the General Hospital of Northern Theater Command between March 2016 and March 2023 were consecutively enrolled. Patients were categorized into clopidogrel and ticagrelor groups based on the P2Y12 receptor inhibitor prescribed at discharge. The primary efficacy endpoint was major adverse cardiovascular events at 12 months, defined as a composite of cardiac death, myocardial infarction, or ischemic stroke. The primary safety endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding. Multivariable Cox proportional hazards regression models were used to compare outcomes between the two groups. Results: A total of 3 323 SMuRF-less ACS patients were included (age (61.8±10.6) years; 1 120 (33.7%) female), comprising 2 694 (81.1%) in the clopidogrel group and 629(18.9%) in the ticagrelor group. Compared with the clopidogrel group, the ticagrelor group had a higher proportion of acute myocardial infarction, younger age, a higher proportion of males, and higher estimated glomerular filtration rate and hemoglobin levels (all P<0.05). During the 12-month follow-up, the incidence of the primary efficacy endpoint, major adverse cardiovascular events, did not differ significantly between the ticagrelor and clopidogrel groups (1.4% (9/629) vs. 2.0% (55/2 694), HR=0.90, 95%CI: 0.43-1.87, P=0.778). However, the ticagrelor group had a significantly higher incidence of the primary safety endpoint, Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, compared with the clopidogrel group (9.2% (58/629) vs. 5.9% (160/2 694), HR=1.79, 95%CI: 1.30-2.47, P<0.001). Conclusions: Among SMuRF-less ACS patients undergoing PCI, ticagrelor did not reduce ischemic events compared with clopidogrel, but was associated with a significantly higher bleeding risk. Clopidogrel may represent a more appropriate P2Y₁₂ receptor inhibitor for this population. 目的： 评估真实世界中无传统心血管危险因素的急性冠脉综合征（ACS）患者在经皮冠状动脉介入治疗（PCI）术后使用替格瑞洛和氯吡格雷的有效性和安全性。 方法： 本研究是一项基于单中心前瞻性PCI注册数据库的回顾性队列研究，连续纳入2016年3月至2023年3月在解放军北部战区总医院住院并接受PCI治疗的无传统心血管危险因素（入院时无高血压、糖尿病、高脂血症或活动性吸烟）的ACS患者，根据患者出院使用的P2Y12受体抑制剂种类分为氯吡格雷组和替格瑞洛组。PCI术后随访12个月，主要有效性终点为主要不良心血管事件，定义为心原性死亡、心肌梗死或缺血性卒中的复合终点；主要安全性终点为出血学术研究联合会2、3、5型出血事件。采用多因素Cox回归模型比较两组终点事件的差异。 结果： 共纳入3 323例无传统心血管危险因素的ACS患者，年龄（61.8±10.6）岁，女性1 120例（33.7%），其中氯吡格雷组2 694例（81.1%），替格瑞洛组629例（18.9%）。与氯吡格雷组相比，替格瑞洛组中急性心肌梗死患者比例较高，年龄较小，女性比例较低，而估算的肾小球滤过率及血红蛋白水平较高（P均<0.05）。随访12个月期间，替格瑞洛组与氯吡格雷组的主要有效性终点即主要不良心血管事件发生率差异无统计学意义［1.4%（9/629）比2.0%（55/2 694），HR=0.90（95%CI：0.43~1.87），P=0.778］。替格瑞洛组主要安全性终点即出血学术研究联合会2、3、5型出血发生率高于氯吡格雷组［9.2%（58/629）比5.9%（160/2 694），HR=1.79（95%CI：1.30~2.47），P<0.001］。 结论： 对于无传统心血管危险因素的ACS患者，与氯吡格雷相比，替格瑞洛未能降低缺血风险，且显著增加出血风险，氯吡格雷可能是该人群更合理的P2Y12受体抑制剂选择。.
A key feature of amyotrophic lateral sclerosis (ALS) pathophysiology is motor neuron hyperexcitability. However, the mechanisms of hyperexcitability are not well understood. Prior studies have used transcranial magnetic stimulation (TMS) to demonstrate increased motor cortex excitability and reduced intracortical inhibition in human ALS. Yet interpretation of these findings is limited because measurement of muscles responses cannot disentangle specific contribution of upper and lower motor neurons and of cortical interneurons to excitability changes. We had the rare opportunity to record directly the corticospinal output evoked by TMS upstream of the spinal circuitry in an ALS patient who had undergone epidural electrode implantation for intractable pain. Single pulse stimulation was performed both with a coil orientation inducing a current that activates corticospinal neurons directly, and with a coil orientation inducing a current that activates corticospinal neurons trans-synaptically. Short interval intracortical inhibition (SICI) was also studied using paired pulse stimulation. Data obtained in the patient were compared with those recorded in 10 conscious control subjects. Compared to control subjects, patient showed a reduced amplitude in response to direct corticospinal neuron activation, yet an enhanced amplitude of corticospinal output after trans-synaptic corticospinal neuron activation together with a SICI reduction. Present findings provide direct evidence of hyperexcitability of monosynaptic glutamatergic inputs to corticospinal neurons that, in association with reduced intracortical inhibition, can trigger neurodegeneration. Taken together with the extensive body of evidence generated by non-invasive TMS studies, the findings from this single-case study may provide valuable insights into the pathophysiological mechanisms of the disease.
Diclofenac (DCF) is a frequently detected pharmaceutical pollutant in wastewater and poses ecological risks due to its persistence during conventional treatment. This study investigates the electro-oxidation (EO) of DCF using three commercially available anode materials (Ti/IrO2, Pt/Ti, and mixed metal oxide (MMO)) under varying operational conditions to identify an optimal balance between oxidation capacity and energy efficiency. The effects of current density (2-20 mA/cm2), initial pH (3.5-9), and initial DCF concentration (5-40 mg/L) on degradation performance, kinetics, and specific energy consumption (SEC) were evaluated. Among the tested anodes, Pt/Ti showed the highest overall performance, achieving 71.2% DCF removal under the optimum conditions (10 mA/cm2, pH 7, and initial DCF concentration 10 mg/L). Under these conditions, the SEC was calculated as 19.7 kWh/g DCF (140 kWh/m3), indicating an effective balance between degradation efficiency and energy consumption. Kinetic analysis revealed that while increasing current density significantly enhanced degradation rates, it also led to a rise in energy demand. The initial DCF concentration was found to have a relatively minor effect on degradation kinetics. The Pt/Ti anode demonstrated a stable performance across a wide pH range, with neutral pH providing slightly more favorable conditions. The overall results indicate that Pt/Ti anodes can provide stable electrochemical performance with moderate energy consumption and represent a feasible electrode option for DCF removal in EO-based treatment systems.
System complexity and limited compatibility with existing infrastructure constrain electro-biogenic wastewater treatment. Here, we present a modular stacked SS316L electrode assembly integrated into a continuous-flow Bioelectrocatalytic Treatment (BET) reactor as a plug-and-play intensification module, enabling in-situ redox regulation without structural modification of conventional sewage treatment plants (STPs) or effluent treatment plants (ETPs). Autonomously generated electrochemical potentials established spatially distributed anodic and cathodic microenvironments, promoting electro-stimulated bioelectrocatalytic activity at the electrode-biofilm interface. Electrochemical characterization demonstrated progressive bioelectrode maturation and enhanced electron-transfer activity, with peak currents reaching 3.8 mA and maximum current and power densities of 10.33 mA m-2 and 11.78 mW m-2, respectively. Over 108 h of continuous operation, the BET reactor achieved significantly higher pollutant removal than the unelectrified control, with Chemical Oxygen Demand (COD), Biochemical Oxygen Demand (BOD5), and Total Organic Carbon (TOC) removal efficiencies of 88%, 89%, and 88%, respectively. Nitrate, sulphate, and phosphate removals reached 84%, 73%, and 81%, respectively. GC-MS profiling revealed substantial reductions in environmentally relevant compounds, including phthalate esters, siloxanes, long-chain hydrocarbons, and phenolic antioxidants, with 80-90% lower peak area signals relative to the influent. 16S rRNA amplicon sequencing revealed distinct shifts in microbial community structure, diversity, and predicted functional potential following electrode integration, indicating electrode-driven microbial adaptation within the BET system. Downstream integration with a triphasic constructed wetland supporting Eichhornia crassipes, Hydrilla verticillata, and Lemna minor facilitated tertiary polishing through rhizospheric plant-microbe interactions and redox stratification. The proposed electro-biogenic intensification strategy offers a scalable and energy-efficient solution for upgrading conventional wastewater treatment infrastructure.
Insulin, an important regulator of peripheral blood glucose levels, can also act in the brain to influence energy metabolism. Insulin receptors are expressed in the dorsomedial hypothalamus (DMH), but nothing is known about the effects of insulin on synaptic function in this region. To determine the effect of insulin on glutamate transmission in the DMH, we used whole-cell patch clamp electrophysiology to examine glutamatergic currents in DMH neurons of young male and female Sprague-Dawley rats. Insulin decreased evoked glutamate current amplitude in both sexes and variance analysis suggested this was due to a postsynaptic change in quantal size. Blocking insulin receptors failed to remove the effect of insulin in both sexes, and further experiments revealed that both insulin receptors (IRs) and insulin-like growth factor-1 receptors (IGF-1Rs), and mechanistic target of rapamycin (mTOR), were necessary to completely block the effects of insulin. Tonic insulin significantly decreased glutamate transmission in the DMH through an IR and mTOR-mediated pathway. Overall, our data suggest that insulin acts through IRs and IGF-1Rs to alter synaptic transmission in the DMH and tonic insulin controls the activity of DMH neurons. This research contributes to our understanding of how insulin acts in the hypothalamus to alter synaptic function, with potential implications for diabetes and obesity research.
The focus of attention (FoA) is a resource within working memory (WM) assumed to hold limited information in a highly accessible state. Recent evidence suggests the FoA can flexibly adjust to hold early, middle, or terminal memory representations in a highly active state with adequate motivation. When a high-reward item is present, the FoA can be redirected to flexibly adjust and select prioritized items, leading to improved performance. This has been termed the prioritization effect. This finding has been demonstrated across prior investigations that have consistently used the color red to indicate the high-reward stimulus. The salience of the stimulus may alternatively explain the prioritization effect in that the salient item may have an easier time entering WM. Salience could influence memory performance through better encoding. The current study aims to test the effect of feature-based confounds (pop-out effect) on reward-based prioritization by using a probe-recognition task and alternating the color of the to-be-prioritized item. Four colors (red, green, blue, magenta) were used, and the color assigned to a higher point-value was randomized between subjects. Our results showed that the prioritization effect was still evident even when salience (pop-out) was controlled. Regardless of the color used there was a performance benefit for the prioritized list position. Comparisons with prior studies indicate that visual pop-out, while not necessary for prioritization, may help facilitate stronger reward effects. Raw trial-level data, statistical analysis, and task code are available in the Open Science Framework (OSF) repository ( https://osf.io/xsc34/overview ). The experiment was not preregistered.
Mitochondria-associated endoplasmic reticulum membrane (MAM), which serves as a signaling hub for interactions between the endoplasmic reticulum (ER) and mitochondria, dynamically coordinates innate immune processes by regulating calcium homeostasis, lipid metabolism, mitochondrial dynamics, mitochondrial protein modifications, and autophagy. MAM regulates calcium homeostasis to govern mitochondrial energy metabolism and inflammasome activation; maintains lipid metabolism for membrane integrity to support antiviral signaling pathways; controls mitochondrial fission and fusion dynamics, processes that are closely associated with mitochondrial DNA (mtDNA) release; regulates mitochondrial protein modifications to fine-tune the function of proteins localized at MAM; and facilitates the clearance of damaged mitochondria and leaked mtDNA through autophagy. Most critically, MAM dysfunction and innate immune dysregulation form a vicious cycle: immune activation disrupts MAM integrity, and MAM abnormalities exacerbate the release of mitochondrial damage-associated molecules, continuously driving overactivation of pathways such as inflammasomes and the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, thereby promoting the development of autoimmune diseases. This review synthesizes current literature on the molecular mechanisms by which MAM regulates innate immunity. We summarize how disruptions in MAM-mediated mitochondrial homeostasis contribute to innate immune imbalance. By integrating these findings, we highlight potential intervention nodes. This underscores the clinical relevance of targeting MAM in immune-related pathological conditions.
Sponges are aquatic animals highly sensitive to environmental changes. They significantly impact silicon cycling by constructing siliceous skeletons. The necessity of better understanding of both biosilification and sponge physiology inspired us to focus current work on how silicon deficiency affects spiculogenesis in the branched Baikal sponges Lubomirskia baikalensis. We employed an original method to detect newly formed silica spicules: staining with a vital fluorescent dye specific to new silica deposition. A significant reduction in spicules formation was observed when silicon levels were decreased from 32 μM (artificial Baikal water) to 10 μM or less, alongside compromised primmorphs integrity. This suggests that low silicon availability may slow sponge growth by limiting spicule production. If such reductions occur naturally, they could alter sponge appearance or abundance, highly affecting Baikal's benthic communities. Our findings, consistent with previous studies, indicate a recent shift in the silicon-to-phosphorus ratio in the coastal Baikal waters, characterized by a decrease in silicon concentration. The notable reduction in siliceous sponges coincides with this trend. Further in vivo experiments are required to test the hypothesis that silicon deficiency affects both the growth and health of sponges in nature, thereby increasing their susceptibility to environmental stressors. Additionally, we examined nitrogen and phosphorus's impact on spicule formation. Seasonal fluctuations in these nutrients are unlikely to directly affect spiculogenesis, though surprisingly, higher nitrogen levels appeared to accelerate spicule growth. Our observations have broader implications, given global and anthropogenic influences on biogenic element levels in the coastal zones of aquatic ecosystems.
Ulcerative colitis (UC) is a chronic, relapsing, immune-mediated inflammatory disease of the colonic mucosa that imposes a substantial and growing global health burden. The pathophysiological basis of UC encompasses a multifactorial interplay among genetic predisposition, dysregulated innate and adaptive immune responses, gut microbiome dysbiosis, epithelial barrier dysfunction, and environmental triggers. Despite considerable advances in therapeutic strategies over the past two decades ranging from aminosalicylates and corticosteroids to biologic agents targeting TNF-α, integrins, and the IL-12/23 axis, as well as small molecule modulators such as JAK inhibitors and sphingosine-1-phosphate receptor agonists-a substantial proportion of patients either fail to achieve remission or experience loss of response over time, underscoring the continued need for novel therapeutic approaches. This comprehensive review systematically addresses the definition, epidemiology, socioeconomic burden, and unmet clinical needs in UC. The molecular and cellular underpinnings of the disease are discussed in depth, including the roles of key signaling pathways, pattern recognition receptors, cytokine networks, and the gut-immune interface. Clinical features, diagnostic criteria, endoscopic and histological scoring systems, and validated disease activity indices are also described. Current pharmacological therapies are reviewed with regard to mechanisms of action, pivotal clinical trial data, and safety profiles. Emerging investigational strategies including precision biologic agents, next-generation small molecules, microbiome-based therapeutics, and cell and gene therapy approaches are evaluated within a translational framework. A curated synthesis of experimental models of UC induction in rodents is presented, followed by structured tabular summaries of selected naturally derived bioactive compounds and pharmacological drug candidates that have demonstrated protective efficacy in preclinical models of UC. Compounds were selected for tabular inclusion on the basis of three prespecified criteria: (i) availability of at least one peer-reviewed in vivo study conducted in a validated experimental colitis model (DSS, TNBS, and acetic acid); (ii) a clearly described and mechanistically plausible basis of action relevant to UC pathophysiology; and (iii) representation across the principal mechanistic clusters identified in this review. Application of these criteria to the studies included in the final review yielded 29 naturally derived bioactive compounds (Table 1) and 26 pharmacological drug candidates (Table 2) for structured synthesis.
Small-cell lung cancer (SCLC) accounts for 13-15% of lung-cancer diagnoses but nearly one quarter of lung-cancer-related deaths. Until 2015, the combination of platinum-etoposide chemotherapy, thoracic radiotherapy and prophylactic cranial irradiation (PCI) had kept median overall survival broadly stable at ≈ 12 months in extensive-stage (ES-SCLC) and ≈ 24 months in limited-stage (LS-SCLC) disease. We summarise the key therapeutic advances of the last decade. This is a curated narrative review. PubMed/MEDLINE, Embase, ClinicalTrials.gov, FDA and EMA releases and ASCO/ESMO/WCLC abstracts published between January 2015 and May 2025 were searched for phase II/III trials, regulatory approvals and biomarker studies in SCLC. Quantitative pooling was not performed. Practice-changing trials, selected pivotal phase II studies that led to regulatory approval, translational papers that re-defined the molecular taxonomy and informative negative trials were prioritised for in-depth discussion. A PRISMA-style flow diagram (Fig. 1) summarises the selection process. Consolidative thoracic radiotherapy improved 2-year OS in ES-SCLC responders (CREST: 13% vs. 3%; HR 0.84, 95% CI 0.69-1.01) and brain-MRI surveillance preserved cognition while replacing routine PCI in patients with ES-SCLC who had access to neuro-imaging. IMpower133 and CASPIAN established first-line chemo-immunotherapy: adding atezolizumab or durvalumab to platinum-etoposide extended median OS by ≈ 2-3 months (IMpower133: 12.3 vs. 10.3 months, HR 0.70, 95% CI 0.54-0.91; CASPIAN: 13.0 vs. 10.3 months, HR 0.73, 95% CI 0.59-0.91) and approximately doubled 18-month survival; 5-year OS now reaches 12-13%. Lurbinectedin produced a 35% response rate in platinum-sensitive relapse in a single-arm phase II study; the confirmatory phase III ATLANTIS trial was negative. Trilaciclib reduced severe chemotherapy-induced myelosuppression. Molecular profiling re-segregated SCLC into ASCL1- (SCLC-A), NEUROD1- (SCLC-N), POU2F3- (SCLC-P) and YAP1/inflamed-defined (SCLC-I) subtypes, supporting the development of subtype-directed trials. DLL3 has re-emerged as a target via the bispecific engager tarlatamab (DeLLphi-301: ORR 40%, mDOR 12 months) and next-generation antibody-drug conjugates. In LS-SCLC, durvalumab consolidation up to 24 months after chemoradiotherapy improved median OS from 33.4 to 55.9 months (ADRIATIC; HR 0.73, 95% CI 0.57-0.93). Maintenance lurbinectedin plus atezolizumab more than doubled median PFS after induction chemo-immunotherapy in IMforte (5.4 vs. 2.1 months; HR 0.54, 95% CI 0.43-0.67) and improved median OS (13.2 vs. 10.6 months; HR 0.73, 95% CI 0.57-0.95). Several phase III trials in this period were negative (KEYNOTE-604, CheckMate-451, CheckMate-331, SKYSCRAPER-02, ATLANTIS, TAHOE, MERU). SCLC therapy has shifted from uniform cytotoxic treatment to a tiered, mechanism-driven algorithm that incorporates PD-L1 blockade, targeted cytotoxics, myeloprotection and refined radiotherapy, raising long-term survival above 20% in selected populations. From a European-practice perspective, current best practice is platinum-etoposide plus a PD-L1 inhibitor for treatment-naïve ES-SCLC, thoracic consolidation radiotherapy in selected responders, lurbinectedin or DLL3-directed clinical trials at relapse, and durvalumab consolidation after chemoradiation in LS-SCLC. Outstanding challenges include a low absolute survival gain from chemo-IO, the absence of validated predictive biomarkers, lineage plasticity, and unequal global access to new agents.
Climate change is altering mosquito distributions and may reshape the risk of mosquito-borne diseases in the Republic of Korea (ROK). However, nationwide, multi-species projections for medically important mosquitoes remain limited. We compiled 1,969 spatially filtered occurrence records for 18 mosquito species and developed species distribution models using MaxEnt. Environmental predictors included bioclimatic, topographic, and land cover variables. Future distributions were projected for the 2030s, 2050s, and 2070s under SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios using MIROC6 climate data. A Climate Change Vulnerability Index (CCVI) was calculated to compare species-specific range expansion and contraction. Current habitat suitability patterns grouped the 18 species into nationwide, northern-preferring, southwestern-preferring, and southern-preferring distribution types. Topographic Wetness Index (36.6%), elevation (18.6%), and land cover type (18.4%) contributed more strongly to model performance than climatic variables alone. Under SSP5-8.5 in the 2070s, Aedes albopictus and Culex tritaeniorhynchus were projected to expand suitable habitat by 183.4% and 236.5%, respectively, whereas northern-preferring Anopheles species showed marked habitat contraction. Anopheles pullus and Anopheles belenrae were projected to lose 100.0% of their suitable habitat under the highest-emission scenario. The CCVI classified five species, mainly Anopheles, as highly vulnerable, one species as moderately affected, and 12 species as range-expanding. These findings indicate that climate change may substantially reorganize mosquito communities in the ROK, reducing habitat suitability for several malaria vectors while expanding suitable areas for important arbovirus and Japanese encephalitis vectors. Adaptive surveillance and vector management should therefore integrate climate projections with local landscape and hydrological risk factors.
Vitamin D, a pleiotropic steroid hormone, has attracted growing research interest in non-skeletal diseases in recent years. The consensus statement on the role of vitamin D in metabolic health, developed at the 8th International Conference on Controversies in Vitamin D, systematically summarizes the mechanisms and clinical evidence of vitamin D in sarcopenia, cardiovascular diseases, abnormal glucose metabolism, obesity, and metabolic syndrome. The statement emphasizes that low serum 25-hydroxyvitamin D [25 (OH) D] levels are closely associated with various metabolic abnormalities. However, the benefits of vitamin D supplementation remain controversial, particularly in the general population, where its efficacy is still unclear. Based on the full text of the consensus statement, this article provides a systematic interpretation of its development methods, key points, evidence base, and clinical implications. It also discusses the current clinical practice of related disciplines, aiming to provide a reference for clinicians in the rational use of vitamin D. 维生素D作为一种具有多效性作用的类固醇激素，近年来在骨骼以外疾病领域的研究持续升温。第8届维生素D争议国际会议形成的《维生素D在代谢健康中作用的共识声明》系统总结了维生素D在肌少症、心血管疾病、糖代谢异常、肥胖及代谢综合征等方面的机制与临床证据。该共识强调低25-羟维生素D水平与多种代谢异常密切相关，但关于补充维生素D的获益仍存在争议，尤其在一般人群中的效果尚不明确。本文结合共识全文内容，对其形成方法、核心观点、循证依据及临床启示进行系统解读，并结合相关学科的临床实践现状进行分析，以期为临床医生合理应用维生素D提供参考。.
Atrophic acne scarring is a prevalent and psychologically distressing sequela of acne vulgaris, often resulting from insufficient matrix remodeling and collagen loss. While microneedling is a safe treatment, its efficacy as a monotherapy is often limited. Autologous platelet-rich plasma (PRP) is the current gold standard adjuvant, but its high cost and invasiveness restrict its use. Topical insulin has emerged as a cost-effective, non-invasive alternative to promote wound healing. A comprehensive search was conducted across PubMed, Web of Science, CENTRAL, Scopus, and Google Scholar for comparative studies published up to January 2026. Risk of bias was assessed using the RoB-2 and ROBINS-I tools. The primary outcome was significant clinical improvement (>50%). Secondary outcomes included changes in scar severity scores and adverse events. Risk ratios (RRs) and standardized mean differences (SMDs) were pooled with 95% confidence intervals (CIs). Trial sequential analysis was also performed. Five studies involving 256 patients were included. Microneedling with topical insulin was associated with a significantly higher rate of significant clinical improvement compared to PRP (RR = 1.96, 95% CI [1.30-2.95], p < 0.0001). However, the pooled analysis of changes in scar severity scores showed no significant difference between groups (SMD = - 0.52, 95% CI [- 1.44, 0.39], p = 0.26), with high heterogeneity. Regarding safety, there was no significant difference in the risk of post-inflammatory hyperpigmentation (RR = 0.72, 95% CI [0.14-3.62], p = 0.69), and no episodes of hypoglycemia were reported. Microneedling with topical insulin may achieve a higher rate of significant clinical improvement than PRP, with a comparable safety profile. However, given the inconclusive trial sequential analysis, high heterogeneity, and low overall certainty of evidence, these findings should be interpreted with caution. Further adequately powered trials are required to confirm this preliminary signal. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Electrical Discharge Machining (EDM) has emerged as an effective technique for machining difficult-to-cut superalloys such as Waspaloy, which are widely used in aerospace applications due to their superior mechanical strength and thermal stability but exhibit poor machinability under conventional processes. The present study focuses on enhancing EDM performance through the combined use of copper-graphite (Cu-Gr) composite electrodes and eco-friendly dielectric media, along with multi-objective optimization. Composite electrodes with graphite content 5 wt% were fabricated, and machining experiments were conducted under different process parameters, including discharge current, pulse-on time, pulse-off time, and inter-electrode gap. Machining performance was evaluated in terms of material removal rate (MRR), tool wear rate (TWR), and surface roughness (Ra), while surface integrity was analyzed using scanning electron microscopy (SEM). A TOPSIS-based multi-objective optimization approach was employed to determine the optimal machining conditions. The results indicated that discharge current and pulse-on time significantly influence MRR, with a maximum MRR of approximately 0.43 mm3/min achieved at 32 A and 30 µs. The minimum TWR of about 0.06 mm3/min was also observed at 8 A, indicating optimal discharge stability. Surface roughness was minimized to 1.8 μm using the CuGr5 electrode, while eco-friendly sunflower oil dielectric produced superior surface integrity with Ra as low as 1.013 μm and reduced recast layer thickness. Sensitivity analysis revealed non-linear parameter behavior with distinct optimal regions, and uncertainty analysis confirmed high experimental reliability with minimal variability. Multi-objective optimization identified the optimal condition with a performance index of 0.6213. The study demonstrates that the integration of composite electrode, bio-based dielectrics, and optimization techniques significantly enhances machining efficiency, surface quality, and sustainability in EDM of Waspaloy.
Workplace health promotion (WHP) is voluntary activity of employers aimed at improving health and well-being of employees. This study aimed to assess the employees' perceptions of employer-provided WHP activities in Poland as well as to identify factors associated with reported WHP provision and the use of WHP activities among full-time employees aged 18-60 years. This questionnaire-based cross-sectional survey was carried out in December 2025 among 1030 full-time employees aged 18-60 years in Poland using the computer-assisted web interview (CAWI) methodology. Quota sampling was used, with gender, age, and place of residence included into stratification model. Among the respondents, 49.8% worked in private Polish company, 26.6% worked in companies with more than 500 employees. Most of the respondents rated their job satisfaction as rather satisfied (61.2%), 64.2% had non-manual work, and 58.5% worked on fixed daytime hours. Among the respondents (n = 1030), 42.2% declared that their employer offers WHP - 20.1% regularly and 22.1% occasionally. Half of respondents, often (40.7%) or very often (9.9%) used WHP activities available in their workplace. Lack of time was the most common (34.5%) barrier in the use of WHP activities. Job satisfaction was the only socio-demographic variable that differentiated (p < 0.001) uptake of employer-provided WHP activities. Age 18-54 (p < 0.05), living in cities over 500,000 residents (aOR: 1.58; 95%CI: 1.02-2.45; p = 0.04), working in private foreign-owned company (aOR: 2.56; 95%CI:1.72-3.79; p < 0.001), working in company with more than 500 employees (aOR: 2.74; 95%CI: 1.59-4.73; p < 0.001), being rather satisfied (aOR: 3.90; 95%CI: 1.94-7.72; p < 0.001) or very satisfied (aOR: 5.66; 95%CI: 2.65-12.11; p < 0.001) from the current job; manager, director level or executive position (p < 0.05), as well as shift work including night shifts (aOR: 1.90; 95%CI: 1.16-3.11; p = 0.01) or flexible working hours (aOR: 1.95; 95%CI:1.30-2.94; p = 0.001) were significantly associated with higher odds of reporting access to WHP activities. This study provides an overview of WHP activities in Poland. Less than half of full-time employees in Poland reported access to employer-provided WHP, with significant differences by sociodemographic and job-related factors.