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To evaluate the application value of recurrent laryngeal nerve tunnel dissection combined with mesangectomy in en-bloc resection for thyroid cancer. A retrospective analysis was conducted on 174 patients with thyroid cancer diagnosed by preoperative fine-needle aspiration cytology who underwent surgery at Shaoxing Central Hospital from January 2020 to May 2024. These patients (modified surgery group) received en-bloc resection using recurrent laryngeal nerve tunnel dissection combined with mesangectomy, including 143 cases of unilateral radical thyroidectomy, 24 cases of bilateral radical thyroidectomy, and 7 cases of isthmus thyroidectomy. A total of 178 patients diagnosed by preoperative fine-needle aspiration cytology who underwent conventional two-step surgery by the same surgical team during the same period were selected as the conventional surgery group, including 160 cases of unilateral radical thyroidectomy and 18 cases of bilateral radical thyroidectomy. All surgeries were completed successfully. Compared with the conventional surgery group, the modified surgery group showed superior outcomes in terms of operation time, intraoperative blood loss, postoperative drainage duration, and postoperative drainage volume in patients undergoing unilateral radical thyroidectomy; temporary recurrent laryngeal nerve palsy and autologous parathyroid gland transplantation rate in patients undergoing bilateral radical thyroidectomy; as well as length of hospital stay, number of central lymph nodes dissected, and number of level IVB lymph nodes dissected (all P<0.05). As of May 25, 2026, the follow-up period ranged from 15 to 77 months. No adverse events such as recurrence of thyroid cancer were reported in any patient. The modified en-bloc resection of thyroid cancer using recurrent laryngeal nerve tunnel dissection combined with mesangectomy is convenient to perform, achieves thorough lymph node dissection with less intraoperative bleeding, and provides reliable protection of the recurrent laryngeal nerve and parathyroid glands. It is worthy of clinical application. 目的: 探讨喉返神经隧道解剖法结合系膜切除在甲状腺癌整块切除术中的应用价值。方法: 回顾性分析绍兴市中心医院2020年1月至2024年5月共174例经术前穿刺明确诊断为甲状腺癌的手术病例作为改良手术组，术中均采用喉返神经隧道解剖法结合系膜切除开展整块切除术，其中单侧甲状腺癌根治术143例，双侧甲状腺癌根治术24例，峡部癌甲状腺根治7例。选取在同期相同团队进行的共178例经术前穿刺明确诊断为甲状腺癌且采用传统二步法进行手术的病例作为传统手术组，其中单侧甲状腺癌根治术160例，双侧甲状腺癌根治术18例。结果: 两组手术均顺利完成。与传统手术组比较，改良手术组单侧甲状腺癌根治术患者的手术时间、术中出血量、术后引流时间和引流量，双侧甲状腺癌根治术患者的术后暂时性喉返神经麻痹、自体旁腺移植，以及住院时间、中央区淋巴结、ⅣB区淋巴结清扫数等指标均更优（均P<0.05）。截至2026年5月25日，患者随访时间为15~77个月。所有患者均未报告甲状腺癌复发等不良情况。结论: 喉返神经隧道解剖法结合系膜切除行甲状腺癌整块切除术操作方便，创面出血少，淋巴结清扫彻底，可以保护喉返神经及甲状旁腺，值得推广应用。.
Asymptomatic contralateral patent processus vaginalis (CPPV) is commonly detected during the laparoscopic repair of inguinal hernias in children and is a risk factor for metachronous contralateral inguinal hernias (MCIHs). However, predicting CPPV preoperatively is challenging, and evidence on its clinical predictors is limited, particularly regarding sex-specific differences. We aimed to identify preoperative predictors of CPPV and to evaluate sex-specific risk factors. This retrospective observational study was conducted at a single tertiary-care university hospital and included children (aged < 16 years) who underwent single-incision laparoscopic percutaneous extraperitoneal closure for a clinically unilateral inguinal hernia or hydrocele between 2013 and 2024. Those who underwent surgery for a recurrent inguinal hernia, MCIH, or bilateral presentation were excluded. The preoperative clinical characteristics were analyzed. Missing data were addressed using multiple imputation before conducting multivariable logistic regression analyses in the overall and sex-stratified cohorts to determine the independent predictors of CPPV. Overall, 1031 children (502 males, 529 females) were included. CPPV was identified in 511 (49.6%) patients. In the multivariable analysis of the overall cohort, left-sided presentation and history of incarceration were independently associated with CPPV, whereas sex was not. In sex-stratified analyses, hydrocele was independently associated with CPPV in males (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.06-2.45; P = 0.03). In females, left-sided presentation (OR, 2.80; 95% CI, 1.94-4.03; P < 0.001), incarceration history (OR, 5.19; 95% CI, 1.39-19.30; P = 0.014), and older age (OR, 1.01; 95% CI, 1.00-1.01; P = 0.046) were associated with CPPV. Preoperative predictors of CPPV showed sex-specific patterns. Sex was not an independent predictor; however, hydrocele was associated with CPPV in males, whereas, in females, left-sided presentation and incarceration history showed strong independent associations with CPPV. These findings may inform preoperative counseling, operative approach selection, and meticulous contralateral laparoscopic exploration, potentially reducing the risk of subsequent MCIH.
This study aimed to develop and evaluate a deep learning-based surgical navigation system capable of recognizing the ureter, uterine artery, and bladder-uterine dissection plane during minimally invasive gynecologic surgery. An artificial intelligence (AI) model was developed at the University of Tokyo Hospital using videos of prior surgeries. Surgical videos of 27 laparoscopic or robot-assisted total hysterectomies were used to create training and validation datasets, with an additional set of cases serving as an independent test set. Key frames were manually annotated to train segmentation models for the ureter and uterine artery. A separate model visualized loose connective tissue fibers (LCTF) to aid in recognizing the bladder-uterine peritoneal dissection plane. Quantitative performance was assessed using standard segmentation metrics, and a qualitative evaluation was conducted by nine gynecologic surgeons using predefined scoring criteria. The segmentation models achieved moderate quantitative performance, with Dice similarity coefficients of approximately 0.51 for the ureter and 0.45 for the uterine artery. In contrast, qualitative evaluation demonstrated favorable clinical interpretability. The mean recognition scores assigned by nine expert surgeons were 4.12 for the ureter and 3.45 for the uterine artery on a five-point scale, indicating that most structures were recognized clearly with only minor misrecognition. For bladder dissection, visualization of connective tissue fibers enabled identification of the correct dissection plane in the majority of evaluated frames; more than 70-80% of connective tissue was recognizable in most frames, and substantial misrecognition was uncommon. This study demonstrates that a deep learning-based system can recognize three key elements of a total hysterectomy: the ureter, the uterine artery, and the bladder-uterine dissection plane. Despite modest quantitative metrics, qualitative assessments indicated strong clinical utility. These findings establish a foundation for an integrated AI-assisted surgical navigation platform to enhance the safety and standardization of minimally invasive gynecologic surgery.
Cryptococcosis is a severe invasive fungal infection with limited therapeutic options beyond fluconazole-based regimens. Isavuconazole, a broad-spectrum triazole antifungal, has emerged as a potential alternative, although clinical data supporting its use remain scarce. We aimed to evaluate the real-world effectiveness and safety of isavuconazole in patients with different forms of cryptococcosis. A retrospective observational study was conducted at a tertiary-care hospital, including patients with cryptococcosis who received isavuconazole at any treatment phase. Standard microbiological methods were used for pathogen identification and susceptibility testing. Demographic, clinical, and microbiological data were collected. Clinical and microbiological responses and tolerability were assessed at end of treatment or until death. Eight patients with cryptococcosis received isavuconazole, most of whom were immunocompromised. Clinical presentations included pulmonary and disseminated disease, with Cryptococcus neoformans as the predominant species. Isavuconazole was primarily used during the consolidation and maintenance phases, after induction therapy with amphotericin B and flucytosine for 2 weeks in most cases, and as salvage therapy in two patients. It was well tolerated during prolonged treatment (6-12 months). In the two patients with isavuconazole therapeutic drug monitoring, plasma total trough concentrations were within the therapeutic range (5 and 3.5 µg/mL, respectively), whereas cerebrospinal fluid total concentration levels were undetectable. A favorable clinical response was observed in four patients, while three remain on treatment with ongoing clinical improvement; one patient died early. Microbiological clearance was achieved in all culture-positive cases. Isavuconazole demonstrated clinical effectiveness in this cohort of patients across different presentations of cryptococcosis. Treatment was safe and well tolerated, supporting its role as an alternative antifungal option against Cryptococcus, particularly when fluconazole is limited by adverse effects or drug-drug interactions. However, data on central nervous system penetration were limited, and further studies are needed to better define its role in cryptococcal meningitis management.
Subsequent to an intracerebral hemorrhage (ICH), a cascade of neuroinflammatory response drives the process of secondary brain injury. At present, no anti-inflammatory nor neuroprotective pharmacological interventions have been demonstrated to improve functional outcome after ICH. This Phase 2b study was designed to establish the safety and feasibility of CN-105, a neuroprotective and anti-inflammatory pentapeptide designed from the receptor binding region of apolipoprotein E, in patients with acute primary supratentorial ICH. The Singapore CN-105 in Participants with Acute Supratentorial ICH Trial (S-CATCH, NCT03711903) was a randomized, double-blind, placebo-controlled trial involving 60 patients (30 CN-105, 30 placebo) treated within 12 h of symptom onset. Safety was assessed through adverse events (AEs) and serious AEs (SAEs), while efficacy was evaluated using functional outcome measures, including the modified Rankin Scale (mRS) at 90 days. CN-105 was safe and well tolerated in patients with acute ICH, with no significant differences in incidence of SAEs between groups (30% SAEs in placebo vs. 26.7% in CN-105). Notably, fewer patients treated with CN-105 group experienced in-hospital neurological deterioration (0 vs. 10% in placebo). While treatment was not associated with a statistically significant improvement in 90-day mRS, higher proportion of patients treated with CN-105 achieved favorable mRS scores (≤ 3) compared with those in the placebo group (77.8 vs. 66.7%; p = 0.35). This Phase 2b trial confirmed the safety and feasibility of CN-105 administration in the acute setting of ICH. Although no statistically significant improvements in neurological outcomes were found, the observed trends warrant further investigation. Future Phase 3 trials should focus on refining patient selection and assessing the therapeutic efficacy of CN-105 in more targeted subgroups such as those with medium-sized subcortical ICH. Trial registration NCT03711903, https://clinicaltrials.gov/ https://clinicaltrials.gov/study/NCT03711903?term=NCT03711903&rank=1 . Registered 16 October 2018.
The International Prognostic Index (IPI) and IPI related prognostic indexes are widely used for risk-stratification in lymphoma. However, identifying poor prognostic group patients remains a significant objective. This study aimed to develop a predictive prognostic model for DLBCL treated with R-CHOP immunochemotherapy. A cohort comprising 167 individuals newly diagnosed with DLBCL between January 2016 and June 2021 at Jiangsu cancer hospital, Nanjing Medical University were enrolled for investigation. Univariate and multivariate Cox analysis were used for variable selection. The Akaike information criterion (AIC) guided the selection of factors for constructing the nomograms, along with a novel prognostic index for assessing both progression-free survival (PFS) and overall survival (OS). Internal validation was performed with the bootstrap method(B = 1000). Age, Lactate dehydrogenase (LDH), stage, extra-nodal sites and absolute CD4 + T cell counts (ACD4C) were associated with both PFS and OS. These discerned prognostic factors were subsequently employed in constructing nomograms for PFS and OS, respectively. The C-indexes of Internal validation performed with the Bootstrap method were 0.76 (PFS: 95%CI 0.67-0.80),0.81(OS:95%CI 0.72-0.85), respectively. The calibration plots, alongside internal bootstrap resampling, demonstrated commendable consistency between predictions and observations. For enhanced clinical applicability, we devised a novel immune prognostic index, categorizing DLBCL patients into four distinct risk groups: low, low-intermediate, high-intermediate, and high risk, corresponding to 0, 1-2, 3, 4-5 risk factors respectively. Kaplan-Meier analysis underscored the superior discriminatory capacity of the immune index in assessing the prognosis across various risk groups. The proposed immune index is a useful tool to predict the prognosis of DLBCL patients treated with R-CHOP immunochemotherapy in this study.
Breast density is a breast cancer risk factor. The accurate quantification of breast density requires reliable segmentation of dense tissue in mammograms, but it is a challenging task due to large variations in tissue appearance across hospitals and imaging devices. We propose MammoDenseSegNet, a new deep encoder-decoder convolutional neural network designed to enhance segmentation performance through two complementary modules: a) Adaptive dual attention module, which captures long-range spatial and channel interdependencies to provide focused attention on relevant dense tissue areas regardless of their location; and b) Multi kernel receptive field module, which enlarges the network's receptive field at the bottleneck layer to aggregate multi-scale contextual features. Additionally, a multi-scale dice loss with deep supervision guides learning across decoder levels to improve robustness. We evaluated MammoDenseSegNet on two public digital mammogram datasets (VinDR-Mammo and EMBED) and one private dataset, spanning a variety of breast densities and imaging artifacts in a total of 1499 images from 606 women. Statistical analysis was done using generalized linear models accounting for correlation among images from the same women and adjusting for potential confounders (proc genmod, proc mixed, SAS v.9.4, SAS Institute, Cary, NC). MammoDenseSegNet demonstrated consistently high performance across various conditions (with Recall ranging from 0.64 to 0.90 and Dice from 0.63 to 0.91) and significantly (p < 0.001) outperformed the publicly available state-of-the-art algorithm based on the VGG16 (with Recall from 0.04 to 0.91 and Dice from 0.06 to 0.82 across the same conditions). The improvement was largest for low-density tissue, where the baseline algorithm practically fails (with the mean Recall of 0.14 and Dice of 0.16) while MammoDenseSegNet remained clinically useful (with the mean Recall of 0.66 and Dice of 0.63).
Liver retraction is critical for safe and efficient robotic liver transection. Conventional methods often require additional instruments, tacking sutures or continuous bedside assistance. This "How I Do It" article presents our double rubber band technique, which enables stable, hands-free retraction during robotic liver transection. We provide a video demonstration of our standard retraction technique for hemihepatectomy and describe adaptations for complex resections.
Ovarian cancer is a gynecological malignancy associated with high mortality and poses significant clinical challenges in early diagnosis and precision treatment. Although the rapid advancement of artificial intelligence (AI) has introduced novel approaches to this field, a comprehensive bibliometric overview remains lacking. This study aims to fill this gap by providing a systematic bibliometric analysis of this rapidly evolving domain. In this study, the Web of Science Core Collection (WoSCC) was used to retrieve literature on AI applications in ovarian cancer research published from 2006 to the search date (November 19, 2025). Using CiteSpace and VOSviewer, we conducted visual and quantitative analyses of publication trends, countries/regions, institutions, authors, journals, highly cited papers, and keywords. A total of 786 publications were included in the analysis. The annual publication output showed pronounced exponential growth, with a marked acceleration after 2019. China, the United States, and the United Kingdom were the leading contributing countries. Research hotspots centered on AI-assisted diagnosis, prognostic prediction models, radiomics, and biomarker discovery. The evolution of keywords indicated that frontier research has shifted from basic classification toward more advanced areas, including high-grade serous ovarian carcinoma, multimodal learning, and explainable AI. Research on AI in ovarian cancer has progressed rapidly, with international collaboration concentrated among leading contributors such as China, the USA, and the UK. Future efforts should prioritize the development of explainable and robust clinical AI systems, deeper integration of multimodal data, closer collaboration between clinicians and AI researchers, and high-quality data sharing to facilitate the translation of research findings into precise clinical practice.
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We sought to evaluate oxidative changes in premature infants receiving 100% oxygen compared with 30% during deferred cord clamping (DCC). Premature infants born at 220/7 to 286/7 weeks received DCC in conjunction with either 30% (LO Group) or 100% (HI Group) oxygen. Blood was extracted from a preserved umbilical segment and a postnatal sample was collected from umbilical vascular lines within two hours of birth. Reduced-to-oxidized glutathione (GSH/GSSG) ratios were analyzed using liquid chromatography coupled to tandem mass spectrometry. Sixty-eight infants had data available for analysis. The median (IQR) gestational age of infants was 264/7 (246/7, 282/7) weeks in both groups. Among infants receiving 100% versus 30% oxygen, median (IQR) GSH/GSSG ratio were not statistically different in arterial cord blood [7.5 (0.6, 290) vs 37 (1.1, 265), p = 0.52] or venous cord blood [8.4 (2,50) vs 76 (5, 210), p = 0.12] or postnatal samples [14 (2, 290) vs 8 (2, 280), p = 0.98)]. Briefly providing 30% vs. 100% oxygen for 90 seconds during DCC showed no significant difference in GSH/GSSG ratios, but redox effects remain unclear given variability, sample size and limited power. Further studies are needed to ascertain potential oxidative damage during neonatal resuscitation and deferred cord clamping. THIS TRIAL IS REGISTERED ON CLINICALTRIALS. NCT04413097 IMPACT: The effect of oxygen administration during deferred cord clamping on redox status is unclear due to large variability in GSH and GSSG values and small sample size. These data provide some insights about umbilical arterial and venous oxygen levels and the effect of placenta on GSH/GSSG in preterm infants. Further basic and clinical studies are needed to better ascertain the potential for oxidative damage during neonatal resuscitation and deferred cord clamping.
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Although pelvic landmarks have traditionally been used to estimate the femoral head center (FC), their reliability may be limited in patients with developmental dysplasia of the hip (DDH). In contrast, femoral-based reference methods have been insufficiently investigated. This study aimed to evaluate the feasibility and clinical utility of estimating the FC location in DDH using a three-dimensional model derived from trochanteric landmarks. We retrospectively analyzed 128 femurs from 84 female patients with DDH (mean age, 36.9 years) who underwent curved periacetabular osteotomy (CPO) from April 1, 2010, to September 30, 2020, and had no symptoms involving the spine or knee. The FC was estimated using multiple regression models based on the three-dimensional coordinates (x, y, and z) of the greater and lesser trochanter tips. Differences between the estimated and actual FC positions were assessed along all three axes. Correlation coefficients between the estimated and actual FC ranged from 0.725 to 0.875 across the three directions. The mean absolute error was 2-3 mm, with greater errors observed in the anteroposterior direction than in the craniocaudal direction. An estimation error within 3 mm may be considered relatively small in the context of clinically acceptable ranges reported in previous studies for restoring femoral offset and leg length during total hip arthroplasty (THA), supporting the practical applicability of this method in preoperative planning. The accuracy of the present approach was comparable to that reported in healthy populations and exceeded that of previous pelvic landmark-based regression techniques. This trochanter-based three-dimensional method enables clinically acceptable estimation of the FC in patients with DDH and may serve as a useful adjunct for planning of the femoral component when the native FC is difficult to identify.
Mind‑body practices, such as meditation and yoga, involve paying attention to breathing sensations. During these practices, individuals report "interoceptive lapses," moments when attention drifts away from internal bodily sensations. While lapses in attention to the external world have been widely studied, little is known about the physiological and neural mechanisms of interoceptive lapses. Interoceptive lapses may share markers with exteroceptive lapses-such as reaction time variability and default-mode network (DMN) connectivity-but may also depend on distinct brain systems and breathing physiology. We examined behavioral, physiological, and neural signals preceding lapses in a sample of 93 adolescents enriched for GAD and depression symptoms. Participants performed a 20-min breath counting task in the fMRI scanner with simultaneous breath recordings. Lapses were defined as moments when counting errors occurred. The sample was split into training and validation sets to test machine learning models predicting attentional lapses. The strongest predictors were timing and variability of button responses (AUCs > 0.75). Breathing variability and breathing-behavior synchronization showed smaller but generalizable predictive value (AUCs < 0.65). Whole-brain connectivity models also predicted lapses (AUC ≈ 0.65), incorporating the DMN, dorsal and ventral attention, and somatomotor networks. Furthermore, models that included brain connectivity marginally outperformed behavior-only models. Comparisons to previous exteroceptive findings indicate some common markers (e.g., reaction time variability) and some unique markers (e.g., selective perceptual coupling with attentional networks). Although limited by the clinical sample and lack of a control task, these results highlight brain-body markers of interoceptive attention that may inform real-time monitoring during mind-body interventions.
Fungal infections, especially in people with weakened immune systems, are a significant global health burden. Accurate identification of fungal morphology from microscopic images is a critical step in guiding timely antifungal treatment decisions. However, manual morphological assessment remains highly dependent on expert mycologists and is prone to inter-observer variability. In this study, we propose a hybrid deep learning framework that integrates the ConvNeXtV2-Base architecture with a Multi-Head Attention-based Multiple Instance Learning module for automated classification of microscopic fungal morphology images. The framework was evaluated on the open-access DeFungi dataset, consisting of 3696 microscopic images representing five clinically meaningful fungal morphology classes. In comparative experiments, classical vision transformer (ViT) models achieved 91.20% accuracy, while MIL-enhanced ViT models reached 93.99%. The proposed ConvNeXtV2-Base + MIL hybrid method outperformed all evaluated architectures, achieving 98.90% classification accuracy. These results establish a new benchmark for automated fungal morphology classification and highlight the potential of AI-assisted decision-support tools to aid expert mycologists in morphology-based assessment workflows.
In this study, we sought to investigate the relationship between lactate clearance rate per hour (LCRperhour) and 28-day mortality, aiming to determine the inflection point where changes in LCRperhour correspond to significant shifts in mortality risk. We conducted a retrospective analysis using the Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU databases (eICU Collaborative Research Database), including patients with sepsis with a peak lactate level (Lacpeak) ≥ 2 mmol·L-1 within 24 hr of intensive care unit (ICU) admission. Using the key lactate metrics Lacpeak, lactate decline (Lacdecline), and decline duration (Timedecline), we calculated the LCRperhour as: (Lacpeak - Lacdecline) ÷ (Lacpeak × Timedecline). Peak lactate level was the highest lactate measured within the first 24 hrs of ICU admission, and Lacdecline was the first lactate measurement captured after the peak value. We assessed its association with 28-day mortality via odds ratios (ORs) using multivariable logistic regression. We examined the linearity of the relationship using an adjusted restricted cubic spline (RCS) model. We stratified patients into high- and low-lactate-clearance groups on the basis of the RCS inflection point. We conducted a subgroup mortality analysis for patients with a Lacpeak below or above 4 mmol·L-1. We retrospectively analyzed data from 53,150 patients from the MIMIC-IV database and 55,887 patients from the eICU database; of these, 13,586 patients with sepsis met the inclusion criteria. Among these, 3,313 (24.4%) patients died within 28 days. Multivariable logistic regression showed that a higher LCRperhour was significantly associated with reduced 28-day mortality (OR, 0.03; 95% confidence interval, 0.01 to 0.09; P < 0.001). The adjusted RCS model revealed a reverse J-shaped relationship between LCRperhour and 28-day mortality (overall P < 0.001; P for nonlinearity < 0.001), with an inflection point on the OR curve at an LCRperhour value of 0.11. Among patients with high lactate levels (> 4 mmol·L-1) and those with low lactate levels (2-4 mmol·L-1), the mortality was significantly lower in those with a LCRperhour ≥ 0.11 than in those with a LCRperhour < 0.11 (both P < 0.05). In patients with sepsis, the relationship between lactate clearance during resuscitation and 28-day mortality was nonlinear. The mortality rate declined steeply with increasing lactate clearance until a point was reached, after which the survival benefit plateaued. These findings provide new insights for clinicians in defining individualized endpoints for fluid resuscitation in sepsis management. RéSUMé: OBJECTIF: Dans cette étude, nous avons cherché à examiner la relation entre le taux de clairance du lactate par heure (LCRperhour) et la mortalité à 28 jours, dans le but de déterminer le point d’inflexion à partir duquel les variations du LCRperhour correspondent à des changements importants du risque de mortalité. MéTHODES: Nous avons mené une analyse rétrospective à partir des bases de données MIMIC-IV (Medical Information Mart for Intensive Care IV) et eICU (eICU Collaborative Research Database), en incluant les individus en sepsis dont le taux de lactate maximal (Lacpeak) était ≥ 2 mmol·L−1 dans les 24 h suivant leur admission à l’unité de soins intensifs (USI). À partir des principales mesures du lactate, soit le Lacpeak, la valeur de lactate au déclin (Lacdecline) et la durée du déclin (Timedecline), nous avons calculé le LCRperhour selon la formule suivante : (Lacpeak – Lacdecline) ÷ (Lacpeak × Timedecline). Le taux de lactate maximal correspondait à la valeur la plus élevée mesurée au cours des premières 24 h suivant l’admission à l’USI, et le Lacdecline à la première mesure du lactate obtenue après la valeur maximale. Nous avons évalué son association avec la mortalité à 28 jours au moyen de rapports de cotes (RC) issus d’une régression logistique multivariable. La linéarité de la relation a été évaluée à l’aide d’un modèle de splines cubiques restreintes (SCR) ajusté. Nous avons stratifié les personnes traitées en groupes à clairance élevée et à clairance faible selon le point d’inflexion du modèle SCR. Une analyse de la mortalité en sous-groupes a été réalisée pour les personnes dont le Lacpeak était inférieur ou supérieur à 4 mmol·L−1. RéSULTATS: Nous avons analysé rétrospectivement les données de 53 150 personnes de la base de données MIMIC-IV et 55 887 personnes de la base de données eICU; parmi celles-ci, 13 586 personnes en sepsis répondaient aux critères d’inclusion. De ce nombre, 3313 (24,4 %) sont décédées dans les 28 jours suivant leur admission. La régression logistique multivariable a montré qu’un LCRperhour plus élevé était significativement associé à une réduction de la mortalité à 28 jours (RC, 0,03; intervalle de confiance à 95 %, 0,01 à 0,09; P < 0,001). Le modèle SCR ajusté a révélé une relation en J inversé entre le LCRperhour et la mortalité à 28 jours (P global < 0,001; P de non-linéarité < 0,001), avec un point d’inflexion sur la courbe des RC à une valeur de LCRperhour de 0,11. Chez les personnes présentant un taux de lactate élevé (> 4 mmol·L−1) et chez celles présentant un taux de lactate faible (2–4 mmol·L−1), la mortalité était nettement plus faible parmi celles dont le LCRperhour était ≥ 0,11 que parmi celles dont le LCRperhour était < 0,11 (P < 0,05 dans les deux cas). CONCLUSION: En contexte de sepsis, la relation entre la clairance du lactate durant la réanimation et la mortalité à 28 jours était non linéaire. Le taux de mortalité diminuait fortement à mesure que la clairance du lactate augmentait, jusqu'à un point au-delà duquel l’effet protecteur sur la survie atteignait un plateau. Ces résultats offrent de nouvelles perspectives aux équipes cliniques pour définir des critères d'évaluation individualisés de réanimation liquidienne dans la prise en charge du sepsis.
To explore the active components and potential molecular mechanisms of Xiangsha Liujunzi decoction (XSLJZ) in the treatment of thyroid cancer. Active components and corresponding targets of XSLJZ were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Thyroid cancer-related targets were collected from seven bioinformatics databases, including GeneCards, OMIM, DisGeNET, DrugBank, TCGA, GEO, and TTD. A protein-protein interaction (PPI) network and a multi-level "XSLJZ-medicinal materials-active components-potential targets-thyroid cancer" network were constructed to identify core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by molecular docking to assess binding affinities. In vitro, CCK-8, flow cytometry, colony formation, Transwell, and Western blotting assays were used to evaluate cell proliferation, death, colony formation, migration, and protein expression in 8505C and TPC-1 thyroid cancer cells. In vivo, a subcutaneous xenograft model was established in female BALB/c nude mice (6-8 weeks old, 15-16 g) by injecting 2×106 8505C cells. Mice were randomly divided into model control (vehicle), low-dose XSLJZ (2 mg/kg), and high-dose XSLJZ (4 mg/kg) groups (n=6 per group), receiving daily gavage for 24 days. Tumor volume and body weight were measured every four days. Histopathological changes were observed by HE and immunohistochemical staining. Five major active components of XSLJZ (isoliquiritigenin, naringenin, baicalein, nobiletin, and glycyrrhetinic acid) and 45 core targets for thyroid cancer were identified. XSLJZ and these five components significantly inhibited the proliferation of 8505C and TPC-1 cells without notable toxicity to normal thyroid cells, with isoliquiritigenin showing the most prominent effect. Flow cytometry revealed that XSLJZ (16 mg/mL) induced up to 84.91% death in TPC-1 cells. Molecular docking showed low binding energies between isoliquiritigenin and Akt1, Caspase-3, Caspase-9, and PARP (lowest: －9.9 kcal/mol with PARP). XSLJZ and isoliquiritigenin dose-dependently suppressed colony formation and migration, downregulated RAGE, p-PI3K, and p-Akt, upregulated Bax and mitochondrial cytochrome c, and activated Caspase-3/9-mediated apoptosis and GSDME-dependent pyroptosis via the AGE-RAGE→PI3K/Akt axis. In vivo, both low and high doses of XSLJZ significantly inhibited tumor growth, reduced Akt and Ki-67 expression in tumor tissues (all P<0.05), and showed no obvious toxicity to the heart, liver, or kidneys. XSLJZ inhibits thyroid cancer cell proliferation and induces cell death through multi-component, multi-target synergistic regulation of the AGE-RAGE→PI3K/Akt signaling pathway. 目的: 探究香砂六君子汤（XSLJZ）治疗甲状腺癌的活性成分及潜在分子机制。方法: 利用中药系统药理学数据库与分析平台（TCMSP）筛选XSLJZ的药物有效活性成分及其靶点。运用GeneCards、在线人类孟德尔遗传（OMIM）、DisGENET、DrugBank、癌症基因组图谱（TCGA）、基因表达综合（GEO）数据库及治疗靶点数据库（TTD）等七个生物信息学数据库筛选甲状腺癌相关靶点。通过构建蛋白-蛋白相互作用（PPI）网络和“XSLJZ-药材-活性成分-潜在靶点-甲状腺癌”多层次网络筛选核心靶点，并通过基因本体（GO）功能注释、京都基因和基因组数据库（KEGG）通路进行富集分析，分子对接分析XSLJZ活性成分与靶点的结合能力。体外试验中，通过CCK-8检测细胞活性，流式细胞术检测甲状腺癌细胞死亡情况，克隆形成实验检验甲状腺癌细胞增殖能力，Transwell实验检验甲状腺癌细胞迁移能力，蛋白质印迹法检测目标蛋白表达。取6~8周龄雌性BALB/c裸鼠（体重15~16g）建立皮下移植瘤模型，于裸鼠侧腹部皮下注射2×10⁶/100 µL的8505C细胞悬浮液。一周后，将小鼠随机分为模型对照组（给予赋形剂）、XSLJZ小剂量组（给予XSLJZ 2 mg/kg）和XSLJZ大剂量组（给予XSLJZ 4 mg/kg），均每日一次灌胃，持续24 d，每组6只。每四天测量一次小鼠的体重和肿瘤大小。HE染色和免疫组织化学染色观察组织病理学变化。结果: 筛选出XSLJZ的五种主要活性成分（异甘草素、柚皮素、黄芩素、川陈皮素、甘草次酸）及45个XSLJZ治疗甲状腺癌的核心靶点。CCK-8实验显示，XSLJZ及五种活性成分可显著抑制8505C、TPC-1细胞增殖，对正常甲状腺细胞无明显毒性，以异甘草素抑癌效果最突出。流式细胞术结果显示，XSLJZ及五种活性成分能诱导甲状腺癌细胞死亡，其中16 mg/mL XSLJZ处理后TPC-1细胞死亡率达84.91%;分子对接结果显示异甘草素与Akt1、Caspase-3、Caspase-9及PARP的结合能较低，其中与PARP的结合能低至－9.9 kcal/mol。XSLJZ及异甘草素可呈剂量依赖性抑制甲状腺癌细胞克隆形成与迁移能力，通过阻断AGE-RAGE→PI3K/Akt信号轴下调RAGE、磷酸化PI3K及磷酸化Akt表达，上调促凋亡蛋白Bax与线粒体细胞色素C，同时激活Caspase-3/9介导的凋亡与GSDME依赖的焦亡。体内试验显示，小、大剂量XSLJZ均抑制移植瘤裸鼠的肿瘤生长，下调肿瘤组织Akt和Ki-67表达（均P<0.05），且对小鼠心、肝、肾无明显毒性。结论: XSLJZ通过多成分-多靶点协同调控AGE-RAGE→PI3K/Akt通路抑制甲状腺癌细胞增殖并诱导细胞死亡。.
N7-methylguanosine (m7G) modification plays a critical role in RNA metabolism and is increasingly recognized for its implications in cancer biology. It can influence RNA stability, translation efficiency, and gene expression regulation. However, the specific role of m7G modification and its downstream genes in thyroid carcinoma (THCA) is not well understood. To comprehensively explore the impact of m7G methylation modification and the m7G-related gene ZNF831 on THCA, this study aims to identify key genes influencing m7G modification in THCA, with a particular focus on clarifying the role of ZNF831. This study is expected to further elucidate the pathological mechanisms of THCA and fill the current research gap in this field. Weighted gene co-expression network (WGCNA) analysis was used to evaluate the expression of m7G-related genes in the THCA expression data from the GEO (Gene Expression Omnibus) datasets. Machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO), gradient boosting decision tree (XGBoost), and random forest (RF), were used to identify the feature genes, including GPSM3 and ZNF831, in the TCGA-THCA dataset. Immunohistochemistry was used to identify the expression difference of ZNF831 in 3 THCA tissues and 3 normal tissues. Finally, the changes of proliferation and migration of THCA cells after overexpression of ZNF831 were investigated. This study investigated m7G-related genes in THCA, focusing on ZNF831 as a key tumor suppressor. Differential expression analysis revealed significant dysregulation of m7G-related genes in THCA. Functional and bioinformatics analyses, including gene set enrichment analysis and protein-protein interaction network construction, identified ZNF831 as a candidate gene. Experimental validation demonstrated that ZNF831 overexpression significantly reduced the proliferation and migration of THCA cells. Additionally, tumor microenvironment analysis showed a positive correlation between ZNF831 expression and immune cell infiltration, indicating its potential role in enhancing anti-tumor immunity. These findings underscore the importance of m7G modifications and m7G-related gene ZNF831 in THCA pathogenesis, highlighting their potential as therapeutic targets. Further research is needed to elucidate the molecular mechanisms and explore clinical applications of these findings.
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Subcutaneous natalizumab offers greater convenience than intravenous administration, but pharmacokinetic differences have raised concerns about potential subclinical disease activity. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) are sensitive biomarkers of neuroaxonal damage and astroglial activation. In this prospective, single-center cohort study, consecutive patients with relapsing-remitting multiple sclerosis who transitioned from intravenous to subcutaneous natalizumab were followed for 12 months. Serum sNfL and GFAP were measured at baseline (prior to switch), and at 6 and 12 months using SIMOA technology. Additional clinical outcomes included annualized relapse rate (ARR), EDSS, and MRI activity. 23 patients were included (mean age 43.7 years; 91% female). Median disease duration was 14 years (IQR 8.1-22), median time on natalizumab was 5 years (IQR 3.3-7.9), baseline 2-year ARR was 0.09 ± 0.2, and median EDSS was 2.0 (IQR 2.0-3.5). Median sNfL Z-scores were 0.2 (IQR - 0.3-0.6) at baseline, 0.1 (IQR - 0.4-1.0) at 6 months, and 0.5 (IQR - 0.4-1.1) at 12 months, with no significant change over time (p = 0.401). GFAP levels were similarly stable (87.7, 86.8, and 90.2 pg/mL; p = 0.957). ARR remained low and unchanged (0.09 pre- and post-switch; p = 1.0), with no radiological activity observed. EDSS remained stable over follow-up. In this small real-world cohort, switching from intravenous to subcutaneous natalizumab was associated with stable sNfL and GFAP levels over 12 months, alongside stable conventional clinical and MRI outcomes. These findings provide supplementary biomarker evidence broadly consistent with existing clinical trial and real-world data, but should be interpreted cautiously given the small sample size.