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Compensatory proximal malalignment despite preserved macroscopic gait in pediatric flexible flatfoot: A dual-level analysis of static alignment and dynamic kinematics

by Haojie Wang, Mengxiang Li, Xiaomeng Liang, Weijian Wang, Pengren Luo, Jiaji Zhang, Yuxuan Du, Tan Liu, Boyu Zhang, Xu Wang, Zhefeng Jin, Yilin Zhu, Tao Han

Background & objective

Previous biomechanical studies on pediatric flexible flatfoot have treated the subject as a single analytical unit, thus failing to elucidate mechanical transmission within the lower extremity closed kinetic chain. This study investigates the impact of distal arch collapse on macroscopic gait parameters, static joint alignment, and dynamic kinematic deviation by integrating a dual-level analytical strategy at both the subject and individual limb levels.

Methods

153 children with pediatric flexible flatfoot (25 unilateral, 128 bilateral) were included, and 3D gait data from 306 lower extremities were analyzed. At the subject level, macroscopic spatiotemporal parameters were compared using the Mann-Whitney U test. At the limb level, linear mixed-effects models (LMMs) compared static 3D joint angles and Gait Variable Scores (GVS) between normal feet and flatfeet, treating subject as a random effect and adjusting for age, body mass index (BMI), and unilateral leg length.

Results

At both the subject and limb levels, no significant between-group differences were observed in any core spatiotemporal parameters (e.g., Mean Velocity, Frequency, and Step Width) (P > 0.05). Regarding static joint alignment at the limb level, the static Hip Rotation angle on the flatfoot side exhibited significantly less external rotation (i.e., relative internal rotation) compared to the normal side (−2.11° ± 0.67° vs. −5.79° ± 1.79°, P = 0.043). During dynamic walking, the Hip Abduction/Adduction GVS on the flatfoot side was significantly elevated (P = 0.032). However, comprehensive gait indices, including the GDI and GPS, showed no significant overall between-group differences.

Conclusion

Pediatric flexible flatfoot was associated with subtle proximal biomechanical alterations despite preserved macroscopic gait characteristics. Changes in static hip alignment and dynamic frontal-plane hip kinematics may therefore provide complementary information beyond conventional gait measures, supporting a broader kinetic-chain assessment in clinical evaluation and follow-up.

Are study design characteristics in single-arm trials comparable with those of their objective performance criteria or performance goals? A scoping review

Por: Wang · H. · Chai · Q. · Jin · F. · Feng · Y. · Cao · R. · Liu · Z. · Li · X. · Luo · M. · Tao · L. · Fei · Y.
Objectives

Single-arm trials (SATs) with objective performance criteria (OPCs) or performance goals (PGs) are increasingly used for regulatory approval of medical devices and other interventions. However, the comparability of study design characteristics between SAT and their external comparator sources remains unclear. This scoping review aimed to evaluate the comparability of study design characteristics between SATs and their matched OPC/PG sources.

Design

Scoping review.

Data sources

PubMed, Embase, the Cochrane Library and four Chinese databases—China National Knowledge Infrastructure, Wanfang Data, CQVIP and SinoMed—were searched from inception to 30 April 2026.

Eligibility criteria

We included SATs that used one or more OPCs or PGs as external comparators to evaluate safety and/or effectiveness endpoints and reported specific numerical values of OPCs or PGs.

Data extraction and synthesis

Two reviewers independently screened the retrieved records and extracted data using a standardised form. For each included SAT, we retrieved the cited OPC/PG sources and extracted study design characteristics data (age, sex, health conditions, outcome definitions and measurement time points) for comparison. Age and sex were compared using summary t-tests and ² tests; health conditions were assessed by two clinicians based on eligibility criteria and baseline characteristics. Results were stratified by OPC versus PG.

Results

A total of 1243 records were identified, and 133 SATs were included. Most studies used PGs (84, 63.2%); 34 (25.6%) claimed to use OPCs, and 15 (11.3%) could not be classified. Of the 60 age comparisons available from 41 studies, 30 showed statistically significant differences; of the 82 sex comparisons available from 59 studies, 60 showed significant differences. Health conditions, outcome definitions and time points were assessed descriptively in a subset of studies, and discrepancies were also observed.

Conclusion

Suboptimal comparability of study design characteristics was observed between SATs and their OPC/PG sources, which might influence the treatment effect estimates. Greater attention to the comparability of study design characteristics in SATs with OPC/PGs may improve the validity of evidence.

Feasibility and effects of a multicomponent program incorporating esports on physical and cognitive function among older adults: A non-randomised pilot trial

by Yuta Nemoto, Fumie Otsuka, Shihoko Suzuki, Saori Kataoka, Tomoko Nakanishi, Takuya Ueda, Susumu Ogawa, Sumika Karasawa, Mikiko Shimaoka, Hiroto Narimatsu, Ung-il Chung

Background

Esports (competitive and organised video gaming) may enhance physical and cognitive health in older adults. The aim of this study was to examine the feasibility and effects of a multicomponent program incorporating esports on physical and cognitive function in community-dwelling older adults.

Methods

This parallel, non-randomised controlled trial was conducted in Yokosuka, Kanagawa, Japan. Twenty-six participants who 1) were aged 60 years or older, 2) had no cognitive impairment, 3) had no major health problems, and 4) had no prior experience with digital games were allocated to either the intervention (n = 12) or the control (n = 14) group. Participants in the intervention group attended weekly 90-minute sessions consisting of health education, exercise, and esports for 12 weeks. The feasibility of the program was assessed based on adverse events, participant retention, adherence to the program, engagement in digital games outside the program, enjoyment of the program, and willingness to continue playing esports after the study period. Additionally, psychological status, physical and cognitive function, and body composition were assessed.

Results

No adverse events were reported; 10 of the 12 participants attended ≥80% of the sessions, all participants reported enjoying the program, and no participants dropped out during follow-up. Positive psychological status scores increased from before to after each session among participants in the intervention group. Furthermore, adjusted analyses showed more favourable changes in gait speed and balance in the intervention group than in the control group (p < 0.05). However, the effects on physical function remain uncertain because the analyses were exploratory.

Conclusions

The program showed potential for high retention and adherence among older adults, with no adverse events. Larger-scale trials are needed to confirm the effectiveness of this intervention program, as the analyses in this study were exploratory.

Trial registration

The study protocol was registered with the UMIN-CTR (ID: UMIN000055350; date of first registration: 27 August 2024).

Sodium-glucose cotransporter 2 inhibitors for diabetic neuropathy: a protocol for a systematic review and meta-analysis

Por: Tao · W. · Yu · Y. · Huang · X. · Huang · J. · Wu · X. · Yu · R. · Xiao · F.
Introduction

Diabetic neuropathy is one of the most common and disabling complications of diabetes mellitus. Current management strategies are largely limited to glycaemic control and symptomatic relief, and few therapies have demonstrated definitive disease-modifying effects. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown multiple metabolic and vascular benefits. However, the efficacy and safety of SGLT2 inhibitors as adjunctive therapy for diabetic neuropathy have not yet been systematically evaluated. This protocol aims to describe the methodology for a systematic review and meta-analysis that will comprehensively assess the therapeutic value of SGLT2 inhibitors in diabetic neuropathy.

Methods and analysis

A systematic search will be conducted in PubMed, Embase, Cochrane Library and Web of Science, as well as in clinical trial registries including the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov, from database inception to 31 May 2026. Eligible studies will include randomised controlled trials evaluating SGLT2 inhibitors in combination with conventional therapy in patients with diabetic neuropathy. Two reviewers will independently perform study selection, data extraction and methodological quality assessment. Extracted data will include study characteristics, participant demographics, intervention details, outcome measures and adverse events. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool. Quantitative synthesis will be conducted using meta-analytic methods, with the choice of statistical model determined by the degree of heterogeneity, as assessed by Cochran’s Q test and the I² statistic. Where appropriate, meta-regression, subgroup analyses, sensitivity analyses and trial sequential analysis will be performed. Publication bias will be assessed using funnel plots and Egger’s regression test, and the certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

Ethical approval is not required because this study will involve only the analysis of published data. The findings will be disseminated through publication in a peer-reviewed journal.

PROSPERO registration number

CRD420261389933.

Endovascular thrombectomy alone versus intravenous thrombolysis plus endovascular thrombectomy on acute basilar artery occlusion (ATTENTION IV): study protocol for a multicentre randomised controlled trial

Por: Li · R. · Nguyen · T. N. · Tao · C. · Sun · J. · Xu · P. · Luo · C. · Wang · L. · Liu · T. · Song · J. · Jing · X. · Wang · A. · Qureshi · A. I. · Abdalkader · M. · Saver · J. L. · Nogueira · R. G. · Hu · W.
Introduction

The DEVT and DIRECT-MT trials showed that endovascular thrombectomy (EVT) alone is non-inferior to intravenous thrombolysis (IVT) followed by EVT in achieving 90-day functional independence for stroke patients with large-vessel occlusion (LVO). However, it is unclear whether EVT alone is non-inferior to IVT followed by EVT among patients with acute basilar artery occlusion (BAO). Therefore, additional studies are needed to explore the potential benefits of EVT alone in these patients.

Methods and analysis

The ATTENTION IV trial is a prospective, multicentre, non-inferiority, blinded endpoint assessment, randomised controlled clinical trial to assess the effect of EVT alone compared with IVT plus EVT in acute BAO patients within 4.5 hours of symptom onset. Patients will be randomised in a 1:1 ratio to either the EVT-alone group or the IVT-plus-EVT group. A score of 0–2 on the 90-day modified Rankin Scale (mRS) was designated as the primary outcome for this study. Primary analysis will follow the intention-to-treat principle with a 15% non-inferiority margin. Secondary outcomes encompass functional status (mRS shift, excellent/good/fair outcomes), quality of life, early neurological recovery and radiological outcomes alongside safety endpoints of intracerebral haemorrhage and mortality.

Ethics and dissemination

This study has been approved by the Ethics Committee of the First Affiliated Hospital of the University of Science and Technology of China (2023KY-055) and will be conducted following the Declaration of Helsinki. Study results will be published in peer-reviewed academic journals.

Trial registration number

ClinicalTrials.gov (NCT05827042).

Tanshinone IIA attenuates cognitive impairment in vascular dementia rats by modulating copper homeostasis via the SLC31A1/FDX1 axis

by Hongxiao Lv, Xinyu Yang, Yutong Liu, Junwei Zhou, Wentao Yu

Background

Tanshinone IIA (TSA) is the core liposoluble active component of Salvia miltiorrhiza, a traditional Chinese medicine, and exhibits multiple pharmacological activities including anti-inflammation, anti-oxidation, anti-apoptosis and mitochondrial function improvement. Studies have confirmed that TSA can ameliorate cognitive function in rats with vascular dementia (VaD) by alleviating cerebral ischemic injury, inhibiting neuroinflammation, protecting the blood-brain barrier and other pathways. However, it has not been reported whether TSA exerts its neuroprotective effect by regulating the cuproptosis pathway. Focusing on cuproptosis, this study investigated the effects of TSA on cognitive impairment, neuronal injury and cuproptosis-related mechanisms in a rat model of VaD.

Methods

A rat model of VaD was established by permanent bilateral common carotid artery ligation (2-VO), and the model rats were treated with TSA. The cognitive impairment of VaD rats was evaluated by the Morris water maze test. Hematoxylin-eosin (HE) staining and Nissl staining were used to detect neuronal injury and loss in the hippocampus of VaD rats. Transmission electron microscopy (TEM) was performed to observe the ultrastructure of mitochondria in the hippocampus; Western blot (WB) assay was adopted to detect the expression levels of cuproptosis-related proteins, including solute carrier family 31 member 1 (SLC31A1), ferredoxin 1 (FDX1), lipoic acid synthetase (LIAS) and dihydrolipoamide transacetylase (DLAT).In vitro, an oxygen-glucose deprivation/reoxygenation (OGD/R) model was established in HT-22 cells to evaluate the effects of TSA on cell viability (CCK-8), intracellular reactive oxygen species (ROS) levels, and copper accumulation (Coppersensor-1 staining), further validating the involvement of copper homeostasis in TSA-mediated neuroprotection.

Results

The results revealed that TSA markedly alleviated cognitive dysfunction and neuronal damage in VaD rats. It also reversed the cuproptosis-related abnormal changes in the brain of VaD rats, and modulated the expression of SLC31A1/FDX1 pathway proteins. In vitro, TSA protected HT-22 cells from OGD/R-induced injury by reducing oxidative stress and copper accumulation.These changes were associated with amelioration of copper overload and mitochondrial damage, suggesting that TSA may exert neuroprotection partially through the regulation of cuproptosis-related pathways.

Conclusion

TSA effectively alleviated cognitive impairment and neuronal injury in VaD rats, and exerted neuroprotective effects both in vivo and in vitro by attenuating copper-dependent cytotoxic stress, preserving mitochondrial integrity, and modulating the SLC31A1/FDX1 axis. This study provides a new perspective and theoretical basis for the future development of targeted drugs for VaD.

Multicentre, double-blind, randomised, placebo-controlled study on the prophylactic use of naldemedine for opioid-induced nausea and vomiting in patients with cancer (POSEIDON study): a protocol paper

Por: Ishihara · Y. · Ohira · M. · Hokabe · M. · Yoshino · S. · Iwashita · K. · Takahashi · K. · Tomita · N. · Uneno · Y. · Kataoka · S. · Kurihashi · T. · Satomi · E. · Hamano · J. · Higashibata · T. · Kosugi · K. · Hirakawa · M. · Kajiura · S. · Ogihara · S. · Kida · M. · Morita · T. · Koretaka
Introduction

Opioid-induced nausea and vomiting (OINV) in patients with cancer imposes a substantial clinical burden and may compromise adherence to opioid therapy. Naldemedine, a peripheral μ-opioid receptor antagonist, is currently approved for the treatment of opioid-induced constipation. Recent evidence suggests similar benefits for the treatment of OINV. This study aims to evaluate the preventive effect of naldemedine on OINV in patients with cancer pain initiating opioid analgesics.

Methods and analysis

This multicentre, double-blind, randomised, placebo-controlled, parallel-group comparison trial will be conducted across 20 hospitals and clinics in Japan. An estimated 120 patients with cancer scheduled to initiate opioid analgesic therapy will be recruited and randomly assigned (1:1) to receive either naldemedine or placebo on day 1 (visit 1). From days 1 to 7, patients will receive blinded study medication concurrently with opioid analgesics and will be followed for 8 days. The primary endpoint will be the proportion of patients achieving a complete response (CR) on day 5, defined as no vomiting and no use of rescue antiemetics for up to 120 hours after initiation of opioid analgesics. Key secondary endpoints will include the proportion of patients achieving CR on days 1, 2, 3 and 7; changes in Numerical Rating Scale scores from baseline; duration of nausea; proportion of patients who experience vomiting; proportion of patients using rescue antiemetics and frequency of rescue antiemetic use. Additionally, the incidence of adverse events and serious adverse events will be recorded throughout the observation period.

Ethics and dissemination

This study has been reviewed and approved by the Hattori Clinic Certified Review Board (approval number: CRB3180027). Written informed consent will be obtained from all participating patients before study commencement. The results of the study will be presented at academic conferences in Japan or overseas and submitted for publication in a peer-reviewed journal.

Trial registration number

NCT07038551 and jRCTs031250128.

The safety window of blood magnesium in pulmonary complications of non-pulmonary sepsis: A U-shaped risk and prognostic analysis based on MIMIC-IV

by Taotao Peng, Yu Li, Yukun Ren, Mi Yang, Zonghong Long, Dukun Zuo, Lu Huang, Huawei Liu, Zhenxin Duan, Hong Li

Pulmonary complications in non-pulmonary sepsis (PC-NPS) are the leading cause of morbidity and mortality in the intensive care unit. Early prevention and monitoring are paramount since the prevention strategies remain limited yet. Magnesium, an essential electrolyte involved in inflammation and vascular regulation, may influence the development of such complications. This retrospective cohort study used data from the MIMIC-IV database to explore the relationship between baseline serum magnesium levels and PC-NPS among 4,836 patients with non-pulmonary sepsis. Survival analysis demonstrated that patients who developed PC-NPS had significantly higher 90-day mortality compared with those without lung injury. When stratified by baseline serum magnesium quartiles, patients in the highest quartile (>2.1 mg/dL) showed the poorest survival. Multivariable logistic regression confirmed that elevated magnesium was independently associated with increased risk of PC-NPS, and restricted cubic spline modeling revealed a U-shaped, nonlinear association between baseline magnesium concentration and PC-NPS risk. Inflection points at 1.26 and 1.91 mg/dL identified a range of relatively lower risk. These findings suggest that baseline serum magnesium levels exhibit a U-shaped relationship with the risk of PC-NPS. Evaluating these levels may aid in clinical prognostication and the exploration of underlying mechanisms.

Balloon pressure monitoring for radial artery hemostasis after transradial coronary procedures: protocol for a randomized controlled trial

by Xiaodong Zhang, Lan Zou, Dunfu Zhang, Bangtao Yao, Junge Chen, Tianfeng Wei, Zhouping Fu, Xin Chang, Lijuan Chen, Yan Geng

Background

Forearm radial artery occlusion (RAO) is a common complication after transradial coronary procedures. Traditional patent hemostasis, relying on operator-dependent assessment, results in labor-intensive processes and inconsistent RAO rates.

Methods

This is a single-center, prospective, randomized, open-label, parallel-group superiority trial. We plan to enroll 818 patients scheduled for transradial coronary angiography. Participants will be randomly assigned (1:1) to either a novel balloon pressure monitoring system (integrating high-precision digital manometry with physiologically-phased decompression) or traditional patent hemostasis. The primary outcome is the incidence of ultrasound-confirmed forearm RAO at 24 hours post-procedure. Key secondary outcomes include rates of access-site vascular complications and bleeding events, as well as objective metrics of hemostasis efficiency. Recruitment Status: Recruitment commenced in September 2024 and is ongoing; the target sample size is anticipated to be reached by May 2026. Analysis will follow the intention-to-treat principle.

Results/ Trial Status

As a protocol paper, no results are reported. The trial is currently in the recruitment phase.

Conclusions

This trial will provide the first large-scale randomized evidence on whether digital manometry-guided compression reduces RAO, potentially bridging the efficacy-effectiveness gap between optimized research protocols and routine practice.

Trial registration

The trial was registered with the Chinese Clinical Trial Registry (ChiCTR) in August 2024, under the registration number ChiCTR2400088258.

Effects of a multidisciplinary transitional care programme on self-management and quality of life in patients undergoing percutaneous coronary intervention: a propensity score-matched analysis

Por: Tao · L. · Luo · D. · Tan · L. · Zhang · C. · Li · Y.
Objectives

Adequate self-management support following percutaneous coronary intervention (PCI) remains a recognised challenge. This study evaluated the Integrated Psychocardiology Transitional Care (IPTC) programme’s effect on self-management and quality of life, and the mechanism of their interaction.

Design

Retrospective cohort study.

Participants

Outcomes were analysed for 697 patients after propensity score matching from an initial PCI registry cohort of 1148.

Primary and secondary outcome measures

The primary outcome was change in Coronary Artery Disease Self-Management Scale Score over 12 months. Secondary outcomes included the Seattle Angina Questionnaire (SAQ), 36-Item Short Form Health Survey (SF-36), Generalised Anxiety Disorder 7 and Patient Health Questionnaire 9 scores. Mixed-effects models and time-lagged mediation analysis were used to examine longitudinal changes and the mediating role of self-management.

Results

No between-group difference in self-management was observed at 1 month. Significant differences in self-management emerged at 3 months, 6 months and 12 months (all px time interaction effects (F=183.1, p

Conclusions

The IPTC programme is associated with improved quality of life in PCI patients, and this association appears to be partly explained by enhanced self-management. These findings suggest that integrating psychology-informed transitional care into post-PCI care may be beneficial.

Utilization of the posterior iliac line for visualizing posterior column screws in obturator oblique view

by Hongtao Li, Li Xu, Longxin An, Xiaojing Li, Linjing Zhang, Jun Liu, Kaili Zhai, Xuecheng Sun, Naibo Feng

Purpose

To evaluate whether posterior column screws penetrate the posterior cortical surface of the acetabulum when assessed using obturator oblique radiographic imaging.

Methods

Computed tomography (CT) scans were performed on the right acetabulum of 50 healthy adults to measure the angle (α) between the posterior wall of the acetabulum and the sagittal plane at the level of the femoral head’s maximal diameter. In addition, five cadaveric pelvises were subjected to C-arm fluoroscopic imaging. A 6 cm long, 1.5 mm Kirschner wire was positioned along the posterior surface of the acetabular posterior column, aligned with the greater sciatic notch, and imaged in both the 45° and α-degree obturator oblique views. The radiographic line visualized from the Kirschner wire in the obturator oblique view was defined as the posterior iliac line, and its anatomical relationship with the posterior surface of the posterior column was analyzed. Subsequently, a 2.5 mm Kirschner wire was inserted into the posterior column at the standard entry point for screw placement using an electric drill, with the wire tip intentionally positioned between the posterior iliac line and the posterior rim in the 45° obturator oblique view. The trajectory of the wire was assessed under both 45° and α-degree obturator oblique views to determine its relation to the osseous corridor.

Results

The measured angle between the posterior surface of the acetabular posterior column and the sagittal plane was (60.2 ± 2.5)°. In the 45° obturator oblique view, the posterior iliac line corresponded with the outer edge of the iliac crest superiorly and the outer edge of the ischium inferiorly, while the posterior wall was projected posterior to the midpoint of the posterior iliac line. In the α° obturator oblique view, the posterior iliac line maintained this alignment but intersected centrally with the posterior acetabular wall. The 2.5 mm Kirschner wire remained within the osseous corridor under the 45° view but potentially extended beyond it under the α° view.

Conclusion

When the posterior column screw is visualized posterior to the posterior iliac line in the 45° obturator oblique view, further assessment using a α° view is necessary. If the screw appears anterior to the posterior iliac line in the α° view, it indicates that the posterior cortical surface has not been breached.

Anti-cancer effect of a novel photodynamic therapy using glucose-linked chlorin e6 conjugated trastuzumab for HER2-positive gastrointestinal cancers

by Makiko Sasaki, Mamoru Tanaka, Akihiro Nomoto, Ryusei Yamasaki, Tomokazu Yoshimura, Shigenobu Yano, Yasunari Sasaki, Yuki Kojima, Taketo Suzuki, Hirotada Nishie, Keiji Ozeki, Takaya Shimura, Eiji Kubota, Hiromi Kataoka

Photodynamic therapy (PDT) is an anti-cancer therapy that employs a photosensitizer (PS) and an optimal wavelength of light, causing a photochemical reaction that releases reactive oxygen species, thereby inducing cancer cell death via oxidative stress. Because light irradiation is limited to the tumor site, PDT has minimal adverse effects. The cancer cell selectivity of the PS is important for reducing damage to the normal mucosa caused by scattered light. Antibody-drug conjugates (ADC) are novel anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a drug bonded through chemical linkers. ADCs enable the targeted delivery of a variety of drugs to cancer cells while minimizing their delivery to healthy tissues. One such tumor surface receptor is the human epidermal growth factor receptor 2 (HER2), which is of interest in the treatment of many cancers, including gastrointestinal cancer. To improve tumor selectivity and minimize damage to the mucosa surrounding the tumor in PDT, we established a novel PS glucose-linked chlorin e6-conjugated trastuzumab (G-Ce6-trastuzumab) that is conjugated to existing PS glucose-linked chlorin e6 (G-Ce6) and evaluated its anti-cancer effect compared to G-Ce6. The effect of PDT was evaluated using HER2-high-expression cells NCI-N87 and HER2-low-expression cells MKN-45. G-Ce6-trastuzumab is internalized by the intracellular organelles in cancer cells. Evaluation of cell death using the WST-8 assay also demonstrated a significantly higher cytotoxic effect of G-Ce6-trastuzumab in HER2-high-expression cells compared with conventional PS G-Ce6. Thereby, G-Ce6-trastuzumab may be an excellent novel PS for PDT because of its strong selectivity for HER2-high-expression cells.

Elucidating key targets and mechanisms of diethyl phthalate-induced colorectal cancer through network toxicology and molecular docking

by Zijing Wang, Liyuan Ma, Zhanyuan Sun, Hengyi Lv, Ruxue Ma, Mengqi Ding, Hai Li, Tao Jiang

Background

Diethyl phthalate (DEP), a widely used plasticizer with endocrine-disrupting properties, has raised concerns regarding its potential carcinogenic effects. However, its precise role in colorectal cancer (CRC) development remains poorly understood.

Methods

The chemical structure of DEP was obtained from the PubChem database. Potential targets of DEP were identified through ChEMBL and STITCH databases and intersected with known CRC-related genes to screen for candidate biomarkers. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways involved. Molecular docking was conducted to predict the binding affinities between DEP and core targets. Finally, 200-ns molecular dynamics (MD) simulations using GROMACS were employed to evaluate the binding stability and dynamic behavior of the DEP–target complexes.

Results

A total of 62 overlapping genes were identified between DEP targets and CRC-associated genes. GO and KEGG enrichment analyses indicated enrichment in epigenetic regulation, chromatin remodeling, and cancer-related signaling pathways, including Notch, TGF-β, and FoxO. Protein–protein interaction analysis identified EP300, EZH2, HDAC1, HDAC2, and KDM1A as key epigenetic regulators. Molecular docking predicted moderate binding affinities between DEP and these targets (−6.6 to −5.7 kcal·mol ⁻ ¹). Subsequent 200-ns MD simulations suggested that DEP formed stable complexes with HDAC1, KDM1A, and EZH2, moderate stability with EP300, and partial dissociation with HDAC2, consistent with hydrophobic and hydrogen-bonding interactions at the binding interfaces.

Conclusion

This study provides a theoretical framework for exploring the molecular mechanisms through which DEP may contribute to CRC development, emphasizing the value of network toxicology in cancer research. These findings may inform future investigations into the risks of DEP exposure and support public health policy and the development of targeted therapeutic strategies.

Double Flap Tibial Transverse Transport Improves Microcirculation and Peripheral Nerve Function in Severe Diabetic Foot Ulcers

ABSTRACT

This retrospective study aimed to evaluate the clinical efficacy of double flap tibial transverse transport (dTTT) in the treatment of Wagner grade 3–4 diabetic foot ulcers (DFUs) and to assess its impact on peripheral nerve function in the affected limb. A total of 25 patients with DFUs who underwent dTTT at our institution were included. Baseline data were collected, and patients were systematically followed at 1, 3, 6 and 12 months postoperatively. Primary outcome measures included wound healing status, postoperative complications, microcirculatory indicators and nerve conduction parameters. All bone transport sites healed successfully, with no major complications observed except for one patient who died from COVID-19. At 12 months postoperatively, significant improvements were noted in foot skin temperature, transcutaneous oxygen partial pressure and the ankle-brachial index (all p < 0.001). Additionally, motor nerve conduction velocities of the posterior tibial and common peroneal nerves increased significantly (p < 0.001), and corresponding compound muscle action potential amplitudes rose to 4.91 ± 0.14 mV and 4.68 ± 0.29 mV, respectively (p < 0.001). These findings suggest that dTTT not only facilitates wound healing by improving local microcirculation but also enhances peripheral nerve function, offering a promising therapeutic approach for improving long-term outcomes and quality of life in patients with advanced DFUs.

Pore network modeling of water and gas transport characteristics in synthetic porous media

by Li Dong, Changkun Ma, Wanghai Tao, Quanjiu Wang

The flow characteristics of water and gas are closely linked to pore structure of porous media, which is of critical importance across various scientific and industrial fields. In this study, synthetic porous media with varying grain sizes and porosity were generated, and their corresponding pore structures were characterized using pore network modeling. Furthermore, the intrinsic permeability, water retention curve, water-gas relative permeability and relative gas diffusivity of the synthetic porous media were simulated via pore network modeling. The results demonstrate that the pore networks extracted from images can effectively distinguish pore structural characteristics. Specifically, the mean pore diameter, throat diameter, and throat length were larger in coarse-grained media compared to fine-grained media of the same porosity. In contrast, fine-grained media exhibited higher values for pore number, throat number, and coordination number. Additionally, the distributions of pore diameter, throat diameter, throat length and coordination were found to follow a lognormal distribution. Porous media with coarse grains and larger porosity exhibit greater intrinsic permeability and relative gas diffusivity compared to media composed of finer grains or lower porosity. The water-retention curves were fitting by van Genuchten model, revealing an exponential relationship between parameter α and throat diameter (or pore diameter). But the parameter n did not show a clear trend across various synthetic porous media, which is attributed to the relatively narrow range of pore size distribution. Similarly, for water-gas relative permeability, the critical water saturation did not vary significantly across different porous media. A strong correlation was observed among the pore structural parameters, irrespective of grain shape and size. Both intrinsic permeability and relative gas diffusivity exhibited a power-law relation with the porosity as well as with pore or throat radius. Moreover, the relationship between intrinsic permeability and relative gas diffusivity can be expressed as k = 166.51(Dp/D0)0.98, which provides a direct means of estimating relative gas diffusion from intrinsic permeability directly.

<i>In-vitro</i> evaluation of probiotic potential of gut microbes isolated from retail chicken

by Sangram Biswas, Lutfor Rahman, Md. Taofiqur Rahman, Susmita Chowdhury, Fahmida Khatun, Azimun Nahar, Sabina Yasmin

Probiotics are live, non-pathogenic microorganisms that help to improve the host’s gut health when administrated in sufficient proportions and are now serving as effective alternatives to antibiotics for managing animal infections and enhancing production. The objective of this study was to isolate, identify and characterize lactic acid bacteria (LAB) strains with excellent probiotic properties from the gastrointestinal tract (GIT) of retail broiler chickens. Samples were enriched in MRS broth at 37°C and plated on MRS agar to isolate distinct colonies of potential probiotic candidates. The isolates underwent a series of standard morphological and biochemical analysis to fulfill the criteria for presumptive identification of LAB and probiotic characteristics. These analyses included Gram staining, catalase testing, hemolytic activity assays, tolerance assays to NaCl, simulated gastric juice and bile salts, antagonistic activity assays, antibiotic susceptibility testing, cell adhesion assay and genotypic identification through 16S rRNA gene sequencing. A total of 40 microbial strains were isolated from the GIT of 20 retail broiler chickens. Among these, 4 LAB strains showed the best probiotic results and were genotypically identified as Enterococcus faecium MCI7, Pedicoccus pentosaceus MCI10, Pediococcus pentosaceus MCC6 and Pediococcus pentosaceus MCC12. The selected strains exhibited non-hemolytic activity and were able to survive in simulated gastric juice at pH 3. Furthermore, the strains displayed bile salt tolerance in the presence of 0.3% bile salt for 4 hours, ranging from 21.91 to 32.77% and a wide range of antimicrobial activities against various pathogenic bacterial strains with inhibition zones ranging from 10 to 16.5 mm. Moreover, three P. pentosaceus strains (MCI10, MCC6, MCC12) were sensitive to most of the tested antibiotics and demonstrated good adherence abilities. Our study identified four LAB strains as promising probiotic candidates for poultry feed additives to effectively establish intestinal microflora, enhance meat quality and growth, and control pathogens.

Real-world optimization of tunnel lengths in tunneled peripherally inserted central catheters for cancer patients: A multi-center retrospective cohort study

by Yinyin Wu, Wei Ding, Yuying Liu, Qianhong Deng, Fengqin Tao, Hanbin Chen, Chang Chen, Meng Xiao, Bilong Feng

Background

Standardized guidelines for optimal tunnel length in tunneled peripherally inserted central catheters (PICCs) are lacking.

Objectives

The objective of this study was to evaluate the real-world impact of tunnel length on clinical outcomes.

Methods

This retrospective cohort study included 207 cancer patients who received tunneled PICCs, categorized into a control group (tunnel length > 4 cm, n = 134) and an observation group (tunnel length ≤ 4 cm, n = 73). Propensity score matching (PSM) was used to address baseline heterogeneity. Cox regression analyses were used to assess the risk of complication during a 120-day follow-up.

Results

Compared to the control group (tunnel length > 4 cm), the observation group (tunnel length ≤ 4 cm) had a significantly higher adjusted overall complication risk (HR = 2.92, 95% CI: 1.07–7.94, P = 0.036) and unplanned catheter removal rate (4.4% vs. 0.0%, P = 0.027), confirming the safety of longer tunnels despite comparable comfort levels between groups. After PSM, Cox regression analysis showed results consistent with those from the unmatched cohort. Subgroup analyses revealed a reduced risk of complications with longer tunnels in patients with BMI ≤ 25 kg/m² (HR = 0.29, 95% CI: 0.11–0.82), without hypertension (HR = 0.36, 95% CI: 0.13–1.00), without diabetes (HR = 0.38, 95% CI: 0.15–0.97), and with solid tumors (HR = 0.31, 95% CI: 0.11–0.85).

Conclusion

The results show that tunnel lengths > 4 cm reduce overall complications and prolong catheter retention, supporting the implementation of standardized protocols while advocating for personalized adjustments based on BMI, comorbidities, and cancer type.

Investigating risk factors of hemorrhagic fever of renal syndrome (HFRS) in Qingdao, Shandong province, China

by Ying Li, Jing Jia, Runze Lu, Liyan Dong, Lizhu Fang, Litao Sun, Zongyi Zhang, Qing Duan, Lijie Zhang, Kunzheng Lv, Huilai Ma

Background

Qingdao, a historically high-risk area for hemorrhagic fever with renal syndrome (HFRS) in China, is undergoing agricultural mechanization and urbanization. However, the specific risk factors for HFRS in this context remain unclear. This study sought to determine the risk factors for HFRS in Qingdao.

Methods

Community-based, 1:2 case-control study. Each case was matched with two healthy neighborhood controls based on biological sex, age, and the same neighborhood or village. Univariate and multivariate conditional logistic regression analyses were performed. Furthermore, stratified analyses were performed to explore risk factor heterogeneity between the peak season for Hantaan virus (HTNV) type HFRS (October-January) and other months.

Results

93 cases (73.2%, 93/127) reported from January 2022 to September 2023 and 186 controls completed this questionnaire. Farmers accounted for the highest proportion (68.8%, 64/93). In multivariate logistic regression analysis, there were three significant risk factors for HFRS: piles of firewood and/or grain in residential yards (odds ratio [OR]=3.75, 95% CI: 2.14–6.55), mite and/or flea bites (OR=1.83, 95% CI: 1.06–3.18) and contacting with rats and/or their excreta (OR=1.73, 95% CI: 1.09–2.74); three variables represented significant protective factors for HFRS: frequency of sun exposure for quilts and bedding (OR=0.41, 95% CI: 0.19–0.90), rodent control measures at home (OR=0.50, 95% CI: 0.30–0.81) and knowing the main sources of HFRS transmission (OR=0.58, 95% CI: 0.36–0.90). Stratified analysis revealed that the influence of these factors varied by season, with rodent contact and control measures being particularly salient during the HTNV peak season.

Conclusion

This study provides the first comprehensive evidence of risk and protective factors for HFRS in Qingdao, highlighting the role of rodent control, promoting comprehensive health education, environmental management, and personal protection. However, the results should be interpreted considering the study’s limitations, including a 73.2% response rate and the potential for recall bias.

Ju-LiteMobileAtt: A lightweight attention network for efficient jujube defect classification

by Xiyuan Zhu, Hongtao Dang, Xiaoyuan Jin, Xun Li

Surface defect detection of organic jujubes is critical for quality assessment. However, conventional machine vision lacks adaptability to polymorphic defects, while deep learning methods face a trade-off—deep architectures are computationally intensive and unsuitable for edge deployment, whereas lightweight models struggle to represent subtle defects. To address this, we propose Ju-LiteMobileAtt, a high-precision lightweight network based on MobileNetV2, featuring two key innovations: First, the Efficient Residual Coordinate Attention Module (EfficientRCAM) integrates spatial encoding and channel interaction for multi-scale feature capture; Second, the Cascaded Residual Coordinate Attention Module (CascadedRCAM) refines features while preserving efficiency. Experiments on the Jujube12000 dataset show Ju-LiteMobileAtt improves accuracy by 1.72% over baseline while significantly reducing parameters, enabling effective real-time edge-based jujube defect detection.

Early enteral nutrition and mortality in mechanically ventilated septic patients receiving vasopressors: A retrospective cohort study using the MIMIC-IV database

by Bo Zou, Fengchan Xi, Tao Gao, Wenkui Yu

Background

The role of early enteral nutrition (EEN) in septic shock remains unclear. This study aimed to evaluate the association between EEN and clinical outcomes in septic patients requiring vasopressor therapy and invasive mechanical ventilation.

Methods

This retrospective cohort study used the MIMIC-IV database and included adult septic patients receiving vasopressors and mechanical ventilation at ICU admission. EEN was defined as enteral nutrition initiated within 48 hours. The primary outcome was 28-day mortality. Secondary outcomes included ICU and hospital length of stay, and duration of mechanical ventilation. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders. Vasopressor dose was stratified based on the maximum norepinephrine-equivalent dose in the first 48 hours: low (0.5). Multivariable regression models were used to assess associations.

Results

A total of 4,673 patients were included, of whom 997 (21.3%) received EEN. Before weighting, EEN was associated with higher 28-day mortality (21.9% vs. 15.3%). After IPTW adjustment, early feeding remained significantly associated with increased mortality (adjusted odds ratio 1.80; 95% confidence interval, 1.42 to 2.27). In stratified analyses, EEN was associated with increased mortality in the medium-dose (odds ratio 1.66; 95% confidence interval, 1.26 to 2.19, p  Conclusions

In critically ill septic patients receiving vasopressors and mechanical ventilation, EEN was associated with increased 28-day mortality, particularly among those receiving medium- or high-dose vasopressor therapy.

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