Unsatisfactory Outcomes Research Articles

Patient Selection, Outcome, and Unhappy Patients in Rhinoplasty.

This article discusses the process of patient selection for rhinoplasties and the many different psychological aspects that come into play. It is important to identify the warning signs and apply a multidisciplinary approach to the surgeons practice, in collaboration with specialist rhinoplasty psychologists. Patients' motivations and surgeon factors are also discussed, as this can lead to unhappy and unsatisfactory postoperative outcomes. Potential reasons for adverse outcomes throughout the pre- and postoperative periods are also described. Finally, a brief guide is provided to reduce the risks of an unhappy patient.

Nanotechnology-driven Microemulsion Based Intranasal Delivery to Neurotechnology-driven Neuralink: Strategies to Improve Management of Neurodegenerative Disorders.

Neurodegenerative disorder refers to malfunctioning of neuronstheirdegradation leading to death of neurons. Among various neurodegenerative disorders APHD (Alzheimer's, Parkinson's, and Huntington's Disease) are particularly concerning due to their progressive and debilitating nature. The therapeutic agent used for treatment and management of APHD often show unsatisfactory clinical outcome owing to poor solubility and limitedpermeability across blood brain barrier (BBB). The nose-to brain delivery can overcome this BBBchallenge as it can transport drug directly to brain though olfactory pathways bypassing BBB. Additionally, the nanotechnology has emerged as a cutting-edge methodology to address this issue and specifically mucoadhesive micro/nanoemulsion can improve the overall performance of the drug when administered intranasally. Beyond the therapy neurotechnology has emerged as are revolutionary AI-driven BCI (Brain computer interface) aimed to restore independence in patients with function loss due to neuron degeneration/death. A promising BCI Neuralink has been recently explored for clinical trials and results revealed that a quadriplegia bearing person with implanted Neuralink chip was able to perform few normal functions of daily routine such as playing online games, text messaging, reading, and learning foreign languages online through accessing the particular websites. This review will discuss the fundamental concepts of neurodegeneration, application of micro/nanoemulsion through intranasal route and integration of neurotechnology for the management and treatment of APHD.

Vitreoschisis-induced vitreous cortex remnants in proliferative vitreoretinopathy: A comprehensive review from basic research to clinical practice.

Proliferative vitreoretinopathy (PVR) significantly impacts the prognosis of rhegmatogenous retinal detachment (RRD), one of the most critical and increasing causes of vision loss in the Western world. Despite advancements in surgical instruments and techniques, the failure rate due to PVR remains substantial, necessitating additional surgeries and often leading to unsatisfactory visual outcomes. This comprehensive review explores the role of vitreoschisis-induced vitreous cortex remnants (VCR) as a critical, previously under-recognised factor contributing to PVR. Vitreoschisis, a phenomenon where the inner lamellae of the posterior vitreous cortex detach while the outermost layers remain attached to the retina, creates VCR that may contain hyalocytes and serve as scaffolds for fibrocellular proliferation. These remnants are difficult to visualise without triamcinolone acetonide (TA) staining, leading to their frequent lack of recognition in clinical practice. Moreover, removing VCR can be challenging and time-consuming, often requiring meticulous surgical techniques to avoid retinal damage and ensure complete elimination. This review consolidates insights from basic research and clinical practice, emphasising the importance of complete vitreous removal and effective VCR detection and removal to mitigate PVR risks. It highlights the histopathological and clinical evidence supporting the hypothesis that VCR, containing hyalocytes, play a pivotal role in preretinal membrane formation. The review also discusses epidemiological data, surgical management strategies and potential future directions, including improved visualisation techniques and the development of new surgical tools and methods. This review aims to improve surgical outcomes and reduce the frequency and burden of RRD-related complications by addressing VCR as a critical factor in PVR.

Ultrasmall Prussian Blue Nanozyme Attenuates Osteoarthritis by Scavenging Reactive Oxygen Species and Regulating Macrophage Phenotype.

Osteoarthritis (OA) is a degenerative joint disease characterized by obscure etiology and unsatisfactory therapeutic outcomes, making the development of new efficient therapies urgent. Superfluous reactive oxygen species (ROS) have historically been considered one of the crucial factors inducing the pathological progression of OA. Ultrasmall Prussian blue nanoparticles (USPBNPs), approximately sub-5 nm in size, are developed by regulating the configuration of polyvinylpyrrolidone chains. USPBNPs display an excellent ROS eliminating capacity and catalase-like activity, capable of decomposing hydrogen peroxide (H2O2) into O2. The anti-inflammatory mechanism of USPBNPs can be attributed to repolarizing macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype by decreasing the ROS levels accompanied by O2 improvement. Additionally, USPBNPs exhibit an exciting therapeutic efficiency against OA, comparable to that of hydrocortisone in vivo. This study not only develops a new therapeutic agent for OA but also offers an estimable insight into the application of the nanozyme.

Progress in Computer-Assisted Navigation for Total Knee Arthroplasty in Treating Knee Osteoarthritis with Extra-Articular Deformity.

Total knee arthroplasty (TKA) is a well-established treatment for end-stage knee osteoarthritis. However, in patients with concomitant extra-articular deformities, conventional TKA techniques may lead to unsatisfactory outcomes and higher complication rates. This review summarizes the application of navigated TKA for treating knee osteoarthritis with extra-articular deformities. The principles and potential benefits of computer navigation systems, including improved component alignment, soft tissue balancing, and restoration of mechanical axis, are discussed. Research studies demonstrate that navigated TKA can effectively correct deformities, relieve pain, and improve postoperative joint function and quality of life compared with conventional methods. The advantages of navigated TKA in terms of surgical precision, lower complication rates, and superior functional recovery are highlighted. Despite challenges like the learning curve and costs, navigated TKA is an increasingly indispensable tool for achieving satisfactory outcomes in TKA for knee osteoarthritis patients with extra-articular deformities.

Open Reduction and Fixation of Late-Presenting Pediatric Supracondylar Humeral Fractures: A Prospective Study.

Supracondylar humeral fracture (SCHF) is a common injury in children, and early treatment provides excellent results and prevents disabilities. Delayed presentation is still prevalent, mainly in developing countries, because many factors hinder the opportunity to receive appropriate treatment. Currently, there are no standard treatment protocols, and there is insufficient published literature on this topic. This study aimed to evaluate the effectiveness and outcomes of open reduction and Kirschner wire fixation using a triceps-sparing posterior approach in neglected cases with complicated fractures. This was a prospective multicenter clinical study conducted between July 2016 and June 2021, which included 28 pediatric patients with neglected SCHF who presented to the hospital for definitive treatment five days or more after initial trauma without previous surgical intervention. All the patients underwent open reduction and K-wire fixation using a posterior triceps-sparing approach. The final functional outcome was assessed using the Mayo Elbow Performance Index (MEPI) and Flynn criteria. All fractures (100%) united within 3-5.5weeks (mean 4 ± 0.7 weeks). Excellent scores observed in 67.9% (n = 19), good in 21.4% (n = 6), fair in 7.1% (n=2), and poor in 3.6% (n = 1) patients according to MEPI. Correspondingly, Flynn's criteria showed 96.4% (n = 27) satisfactory and 3.6% (n = 1) unsatisfactory outcome. Open reduction and fixation using Kirschner wires through the posterior triceps-sparing approach is an effective treatment method for late-presenting SCHF in children with consequent satisfactory results.

A Dopamine-Modified Hyaluronic Acid-Based Mucus Carrying Phytoestrogen and Urinary Exosome for Thin Endometrium Repair.

Thin endometrium (TE) is closely associated with infertility in reproductive medicine. Estrogen therapy gains unsatisfactory outcomes. In this study, an artificial mucus based on dopamine (L-DOPA)-modified hyaluronic acid combining phytoestrogen cajaninstilbene acid and rat urinary exosomes (CUEHD) is constructed for TE treatment using a rat TE model. In the rat TE model, the dominant elastic behavior and adhesive properties of CUEHD guarantee adequate retention, rendering superior synergistic treatment efficacy and favorable biosafety characteristics. CUEHD treatment significantly increases endometrial thickness and promotes receptivity and fertility. Mechanistically, estrogen homeostasis, inflammation inhibition, and endometrial regeneration are achieved through the crosstalk between ER-NLRP3-IL1β and Wnt-β catenin-TGFβ-smad signaling pathways. Moreover, the therapeutic potential of exosomes from human urine and adipose tissue-derived stem cells (ADSCs) and rat ADSCs are also demonstrated, indicating extensive use of the artificial mucus system. Thus, this study illustrates a platform combining phytoestrogen and exosomes with promising implications for TE treatment.

A multifunctional nanoplatform with dual-targeted antibacterial and cascaded immunomodulatory strategy for the treatment of bacterial keratitis

Bacterial keratitis (BK) is a serious ocular infection and frequently cause irreversible damage to the corneal tissue and even blindness. Current clinical treatments using antibiotics achieve unsatisfactory outcomes due to the lower bioavailability, high risks of drug resistance and limited therapeutic functions. To address these challenges, we proposed a dual-targeted antibacterial and cascaded immunomodulatory therapy strategy, constructing a multifunctional nanoplatform (HPBH@GLA/AMP) using the 3-aminophenylboric acid (NBA) and hyaluronic acid (HA) co-modified hollow polydopamine (HPDA) to serve as a functional nanocarrier (HPBH) for loading antimicrobial peptide (AMP) and glycyrrhizic acid (GLA). The HPBH@GLA/AMP presented excellent targeting and bactericidal performance to Pseudomonas aeruginosa (P. aeruginosa), coupled with its capacity to alleviate the bacteria-triggered excessive immune response via an ingenious cascaded immunoregulatory process. Notably, the study of underlying anti-inflammatory mechanism revealed that the functional nanocarrier of HPDA could effectively scavenge the reactive oxygen species (ROS) for controlling early inflammatory responses, while inhibit the expression of late mediator high mobility group box 1 (HMGB1) chemokine through released GLA. Specially, the duel-targeted characteristic enabled this nanoplatform to recognize both the bacteria and inflammatory cells precisely and aggregate the location where bacteria and/or inflammatory cells exist persistently, effectively increased the therapeutic concentration of drugs. Featuring the antibacterial synergistic yet sequential regulation for the inflammatory response, the HPBH@GLA/AMP achieved satisfactory therapeutic effects in a BK mouse model in vivo. This study provides a bright prospect for clinical treatment of refractory bacterial keratitis (BK) and even extended to other immunotherapy in infectious disease.

The failure of the United Kingdom’s accounting and fiscal governance

PurposeThis paper aims to unravel the puzzle that the United Kingdom’s high-quality government accounting and fiscal architecture is associated with low-quality outcomes, including poor productivity growth, high public debt, public services which do not meet citizen expectations and historically high levels of taxation. It contributes to public sector accounting research in the fields of fiscal transparency and governance.Design/methodology/approachThis paper uses Miller and Power’s (2013) economization framework and Dunsire’s (1990) concept of collibration to explain why being a global leader in public sector accounting reform and in fiscal and monetary architecture has not protected the UK from weak governance. The intersection of economization’s roles of accounting with modes of government accounting clarifies the puzzle.FindingsWhereas accruals government accounting contributes to fiscal transparency, this is not a sufficient condition for well-judged policy and its effective application. Collibration is the dominant mechanism for mediation in the fiscally centralized UK, but it has failed to deliver stable outcomes, in part because Parliament is limited in its ability to hold back inappropriate behaviour by the Executive. Subjectivization has disrupted adjudication because governments at all levels resist constraints on their behaviour, with unpredictable and often damaging consequences.Originality/valueThis paper provides insights through the combined lens of economization and modes of government accounting, demonstrating the practical value of this conceptualization. Although some causes for unsatisfactory outcomes are specific to the UK, there are cautions for accounting and fiscal reformers in other countries, such as Member States of the European Union.

Blocking ACSL6 Compromises Autophagy via FLI1-Mediated Downregulation of COLs to Radiosensitize Lung Cancer.

Lung cancer (LC) is the leading cause of cancer-related mortality worldwide. Radiotherapy is the main component of LC treatment; however, its efficacy is often limited by radioresistance development, resulting in unsatisfactory clinical outcomes. Here, we foundthat LC radiosensitivity is up-regulated by decreased expression of long-chain acyl-CoA synthase 6 (ACSL6) after irradiation. Deletion of ACSL6 results in significant elevation of Friend leukemia integration 1 transcription factor (FLI1) and a marked decline of collagens (COLs). Blocking of ACSL6 impairs the tumor growth and upregulates FLI1, which reduces the levels of COLs and compromises irradiation-induced autophagy, leading to considerable therapeutic benefits during radiotherapy. Moreover, the direct interaction between ACSL6 and FLI1 and engagement between FLI1 and COLs indicates the involvement of the ACSL6-FLI1-COL axis. Finally, the potently adjusted autophagy flux reduces its otherwise contributive capability in surviving irradiation stress and leads to satisfactory radiosensitization for LC radiotherapy. These results demonstrate that enhanced ACSL6 expression promotes the aggressive performance of irradiated LC through increased FLI1-COL-mediated autophagy flux. Thus, the ACSL6-FLI1-Col-autophagy axis may be targeted to enhance the radiosensitivity of LC and improve the management of LC in radiotherapy.

Bioderived Nanoparticles for Cardiac Repair.

Biobased therapy represents a promising strategy for myocardial repair. However, the limitations of using live cells, including the risk of immunogenicity of allogeneic cells and inconsistent therapeutic efficacy of autologous cells together with low stability, result in an unsatisfactory clinical outcomes. Therefore, cell-free strategies for cardiac tissue repair have been proposed as alternative strategies. Cell-free strategies, primarily based on the paracrine effects of cellular therapy, have demonstrated their potential to inhibit apoptosis, reduce inflammation, and promote on-site cell migration and proliferation, as well as angiogenesis, after an infarction and have been explored preclinically and clinically. Among various cell-free modalities, bioderived nanoparticles, including adeno-associated virus (AAV), extracellular vesicles, cell membrane-coated nanoparticles, and exosome-mimetic nanovesicles, have emerged as promising strategies due to their improved biological function and therapeutic effect. The main focus of this review is the development of existing cellular nanoparticles and their fundamental working mechanisms, as well as the challenges and opportunities. The key processes and requirements for cardiac tissue repair are summarized first. Various cellular nanoparticle modalities are further highlighted, together with their advantages and limitations. Finally, we discuss various delivery approaches that offer potential pathways for researchers and clinicians to translate cell-free strategies for cardiac tissue repair into clinical practice.

MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells

BackgroundIn spite of significant advancements in theraputic modalities for hepatocellular carcinoma (HCC), there is still a high annual mortality rate with a rising incidence. Major challenges in the HCC clinical managment are related to the development of therapy resistance, and evasion of tumor cells apoptosis which leading unsatisfactory outcomes in HCC patients. Previous investigations have shown that autophagy plays crucial role in contributing to drug resistance development in HCC. Although, miR-29a is known to counteract authophagy, increasing evidence revealed a down-regulation of miR-29a in HCC patients which correlates with poor prognosis. Beside, evidences showed that miR-29a serves as a negative regulator of autophagy in other cancers. In the current study, we aim to investigate the impact of miR-29a on the autophagy and apoptosis in HCC cells using extracellular vesicles (EVs) as a natural delivery system given their potential in the miRNA delivery both in vitro and in vivo. MethodHuman Wharton’s Jelly mesenchymal stromal cell-derived extracellular vesicles were lately isolated through 20,000 or 110,000 × g centrifugation (EV20K or EV110K, respectively), characterized by western blot (WB), scanning electron microscopy (SEM), and dynamic light scattering (DLS). miR-29a was subsequently loaded into these EVs and its loading efficiency was evaluated via RT-qPCR. Comprehensive in vitro and in vivo assessments were then performed on Huh-7 and HepG2 cell lines. ResultsEV20K-miR-29a treatment significantly induces cell apoptosis and reduces both cell proliferation and colony formation in Huh-7 and HepG2 cell lines. In addition, LC3-II/LC3-I ratio was increased while the expression of key autophagy regulators TFEB and ATG9A were downregulated by this treatment. These findings suggest an effective blockade of autophagy by EV20K-miR-29a leading to apoptosis in the HCC cell lines through concomitant targeting of critical mediators within each pathway.

Computed tomography-based radiomics predicts the fibroblast-related gene EZH2 expression level and survival of hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. The primary treatment strategies for HCC currently include liver transplantation and surgical resection. However, these methods often yield unsatisfactory outcomes, leading to a poor prognosis for many patients. This underscores the urgent need to identify and evaluate novel therapeutic targets that can improve the prognosis and survival rate of HCC patients. AIM To construct a radiomics model that can accurately predict the EZH2 expression in HCC. METHODS Gene expression, clinical parameters, HCC-related radiomics, and fibroblast-related genes were acquired from public databases. A gene model was developed, and its clinical efficacy was assessed statistically. Drug sensitivity analysis was conducted with identified hub genes. Radiomics features were extracted and machine learning algorithms were employed to generate a radiomics model related to the hub genes. A nomogram was used to illustrate the prognostic significance of the computed Radscore and the hub genes in the context of HCC patient outcomes. RESULTS EZH2 and NRAS were independent predictors for prognosis of HCC and were utilized to construct a predictive gene model. This model demonstrated robust performance in diagnosing HCC and predicted an unfavorable prognosis. A negative correlation was observed between EZH2 expression and drug sensitivity. Elevated EZH2 expression was linked to poorer prognosis, and its diagnostic value in HCC surpassed that of the risk model. A radiomics model, developed using a logistic algorithm, also showed superior efficiency in predicting EZH2 expression. The Radscore was higher in the group with high EZH2 expression. A nomogram was constructed to visually demonstrate the significant roles of the radiomics model and EZH2 expression in predicting the overall survival of HCC patients. CONCLUSION EZH2 plays significant roles in diagnosing HCC and therapeutic efficacy. A radiomics model, developed using a logistic algorithm, efficiently predicted EZH2 expression and exhibited strong correlation with HCC prognosis.

CCL5/CCR5/CYP1A1 pathway prompts liver cancer cells to survive in the combination of targeted and immunological therapies.

Combination therapy of anti-programmed cell death protein-1 (PD-1) antibodies and tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis for hepatocellular carcinoma (HCC), but many patients still have unsatisfactory outcomes. CD8 T cells are known to exert a pivotal function in the immune response against tumors. Nevertheless, most CD8 T cells in HCC tissues are in a state of exhaustion, losing the cytotoxic activity against malignant cells. Cytokines, mainly secreted by immune cells, play an important role in the occurrence and development of tumors. Here, we demonstrated the changes in exhausted CD8T cells during combination therapy by single-cell RNA sequencing (scRNA-seq) analysis on tumor samples before and after treatment. Combination therapy exerted a substantial impact on the exhausted CD8T cells, particularly in terms of cytokine expression. CCL5 was the most abundantly expressed cytokine in CD8T cells and exhausted CD8T cells, and its expression increased further after treatment. Subsequently, we discovered the CCL5/CCR5/CYP1A1 pathway through RNA sequencing (RNA-seq) on CCL5-stimulated Huh7 cells and verified through a series of experiments that this pathway can mediate the resistance of liver cancer cells to lenvatinib. Tissue experiments showed that after combination therapy, the CCL5/CCR5/CYP1A1 pathway was activated, which can benefit the residual tumor cells to survive treatment. Tumor-bearing mouse experiments demonstrated that bergamottin (BGM), a competitive inhibitor of CYP1A1, can enhance the efficacy of both lenvatinib and combination therapy. Our research revealed one mechanism by which hepatoma cells can survive the combination therapy, providing a theoretical basis for the refined treatment of HCC.

Analysis of condylar positioning in the temporomandibular joint following mandibular reconstruction: Introduction of a new classification system and assessment of influencing factors on displacement.

This study investigates the unsatisfactory outcomes observed in mandibular reconstruction procedures attributed to improper condylar positioning in the Temporomandibular Joint. It also proposes a systematic classification for post-reconstruction condylar positioning dissatisfaction. A retrospective analysis was conducted on 337 patients who underwent tumor removal and mandibular reconstruction with vascularized osteocutaneous flaps. Reconstruction techniques included conventional surgery (43.3%) and 3D technology-guided procedures (56.7%). Evaluation utilized preoperative and postoperative CT scans to assess mandibular vertical ramus length (V) and condylar alignment in both sagittal (S) and coronal (C) planes. Accordingly, a classification system for condylar positioning was developed and abbreviated as VSC. It includes four classes: Class I, proper condylar reconstruction; Class II, short ramus length; Class III, one or two aspects of sagittal/coronal condylar positions dissatisfaction; and Class IV, two or three aspects dissatisfaction. The overall success rate for condylar reconstruction was 85.16%. Though not statistically significant, the success rate was marginally higher in the 3D-assisted group (85.86%) compared to the conventional group (84.25%). In terms of the VSC classification, the distribution of cases across Class I, II, III, and IV were 287, 4, 9, and 37 cases, respectively. Notably, condylar dislocation was significantly associated with the defect site, particularly the body and condyle (p < 0.001, OR = 49.734, 95% CI 12.995-190.342), and the number of reconstructed segments (p = 0.025, OR = 3.480, 95% CI 1.173-10.328). The findings highlight the importance of accurate reconstruction methods and reveal implications of the defect site and the number of reconstructed segments in condylar dislocation. Consequently, we propose a classification system to refine condylar positioning assessment and enhance surgical outcomes in mandibular reconstruction.

Efficacy and safety of peroral endoscopic myotomy for pediatric achalasia: A nationwide study.

Achalasia, a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter to relax and loss of esophageal peristalsis, significantly impacts pediatric patient quality of life through symptoms like dysphagia, chest pain, and weight loss. This nationwide retrospective cohort study evaluates the efficacy and safety of peroral endoscopic myotomy (POEM) for pediatric achalasia in Mongolia, contributing to the limited global data on this minimally invasive treatment in children. Conducted between February 2020 and March 2022 at 2 tertiary centers, the study included symptomatic achalasia patients, treatment-naive or those with unsatisfactory outcomes from previous esophageal dilations. The POEM procedure was assessed for its impact on esophageal structure and function, symptom severity via the Eckardt score, and procedure-related safety, with outcomes measured at baseline, 3 days, and 12 months post-procedure. The study demonstrated notable post-procedure improvements across all measured outcomes: abnormal contraction length and esophageal width significantly reduced, underscoring the procedure's effectiveness. More precisely, the integrated relaxation pressure showed a significant improvement from a mean of 26.8 mm Hg (standard deviation [SD], 5.4 mm Hg) pre-procedure to 10.8 mm Hg (SD, 1.1 mm Hg) 12 months (P < .001). Similarly, Eckardt scores, which assess symptom severity, improved significantly from a pre-procedure mean of 7.0 (SD, 1.0) to a substantially lower score post-procedure (P < .001), reflecting enhanced patient quality of life and symptom alleviation. This study underscores POEM's role as an effective, minimally invasive option for pediatric achalasia management within the Mongolian population, offering significant symptomatic relief and improved esophageal function.

Conservative treatment of intraperitoneal bladder perforations: a conscious choice or forced measure

Intraperitoneal traumatic perforations of the bladder of any origin (e.g., external trauma, iatrogenic injuries) and spontaneous ruptures are conditions that, according to the canons of surgery, require emergency surgical intervention by one or another access. However, some studies have indicated the possibility of conservative management of such patients — both adults and children. A review of publications describing the results of conservative treatment of patients with intraperitoneal bladder perforations was performed. Overall, 2,679 publications related to intraperitoneal perforations of the bladder were found in the available scientific databases, of which only 72 focused on issues of conservative treatment. In 13 of them, the possibility of such an approach is denied, but without reference to their own material. Analysis of the literature demonstrated that conservative management of intraperitoneal perforations of the may be feasible in certain circumstances, sometimes being a crucial measure. Indications for conservative treatment techniques include the absence of peritonitis, small perforation size, and short periods from the moment of perforation. However, all these indications are in the nature of opinions and assumptions and are not part of algorithmic tactics. The effectiveness of this approach remains unclear. The frequency of unsatisfactory outcomes ranges from 10% to 50%, which indicates the inappropriateness of conservative treatment. With the small number of studies and conflicting results obtained prohibits us to consider this technique as the method of choice for treating patients with intraperitoneal perforations of the bladder.

Endoscopic retrograde cholangiopancreatography using a pediatric colonoscope in patients with Roux‑en‑Y gastrectomy and an intact major duodenal papilla.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastrectomy and an intact major duodenal papilla is challenging and difficult, with unsatisfactory outcomes using various endoscopes. Limited data are available regarding the outcomes of ERCP using a pediatric colonoscope in such patients. To evaluate the efficacy of a pediatric colonoscope in patients with Roux-en-Y gastrectomy and an major duodenal intact papilla, 93 consecutive patients with Roux-en-Y gastrectomy and an intact major duodenal papilla who underwent ERCP using a pediatric colonoscope at the Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, (Nanjing, China) between January 2018 and December 2022 were retrospectively reviewed. Following the failure of bile duct cannulation, a double-guidewire or precut technique was utilized for advanced cannulation. Interventions were performed using standard ERCP therapeutic accessories. The results indicated that distal gastrectomy with Roux-en-Y reconstruction was performed in 38 out of 93 patients, while 55 patients underwent total gastrectomy with Roux-en-Y reconstruction. The success rates associated with endoscope insertion, endoscopic cannulation and therapeutic ERCP were 88.17% (82/93), 85.37% (70/82) and 95.71% (67/70), respectively, while the clinical intervention success and complication rates were 72.04% (67/93) and 7.53% (7/93), respectively. The endoscope insertion time was 40.78±10.04 min, and the ERCP procedure time was 88.55±16.38 min. Student's t-test showed that the endoscope insertion time and the ERCP procedure time in patients undergoing distal gastrectomy were longer than those in patients undergoing total gastrectomy (P<0.05). Binary logistic regression analysis showed that age and number of previous abdominal surgeries were independent risk factors associated with endoscope insertion failure. In conclusion, the present study demonstrated that the use of a pediatric colonoscope is efficacious and safe for patients with Roux-en-Y gastrectomy and an intact major duodenal papilla undergoing ERCP.

Acidity-Responsive Fe-PDA@CaCO3 Nanoparticles for Photothermal-Enhanced Calcium-Overload- and Reactive-Oxygen-Species-Mediated Tumor Therapy.

Calcium-overload-mediated tumor therapy has received considerable interest in oncology. However, its efficacy has been proven to be inadequate due to insufficient calcium ion concentration at the tumor site coupled with challenges in facilitating efficient calcium uptake by tumors, leading to unsatisfactory therapeutic outcomes. In the present study, calcium carbonate nanoshell mineralized ferric polydopamine nanoparticles (Fe-PDA@CaCO3 NPs) were prepared for achieving Ca2+-overload-mediated tumor therapy. Upon entering the tumor site, the pH-responsive CaCO3 layer, acting as a "Ca2+ storage pool", rapidly degraded and released high quantities of free Ca2+ within the weakly acidic environment. The Fe-PDA core, with its excellent photothermal conversion properties, could significantly increase the temperature upon exposure to near-infrared (NIR) light irradiation, thereby activating the TRPV1 channel and leading to a large influx of released Ca2+ into the cytoplasm. Furthermore, the exposed Fe-PDA core could react with the tumor-overexpressed hydrogen peroxide (H2O2) to efficiently produce hydroxyl radicals (•OH), significantly increasing intracellular reactive oxygen species (ROS) levels and thus inhibiting the activity of the Ca2+ efflux pump, resulting in a high intracellular Ca2+ concentration. Ultimately, the increase in calcium/ROS levels could disrupt mitochondrial homeostasis and activate the apoptosis pathway. The current work presents a promising approach for tumor therapy using photothermal-enhanced calcium-overload-mediated ion interference therapy and chemodynamic therapy.

Clinical efficacy of gamma-oryzanol combined with Femoston for perimenopausal syndrome.

Perimenopausal syndrome (PMS) is a chronic disease associated with estrogen deficiency. Because of the unsatisfactory outcomes of current conventional treatments for this condition, its treatment must be continuously explored and optimized. To assess the clinical effectiveness of γ-oryzanol in combination with Femoston for PMS. A total of 119 patients with PMS were selected from June 2023 to December 2023, which included 59 and 60 patients in the control and observation group, respectively. The control and observation groups were treated with Femoston and γ-oryzanol + Femoston, respectively. Comparative analyses were performed in terms of clinical effectiveness, safety (dizziness and headache, nausea and vomiting, and breast tenderness), sex hormones [estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)], lumbar spine (L1-4) and bilateral femoral bone mineral density (BMD), and sleep quality (sleeping time and frequency of awakenings from sleep). Compared with the control group, the observation group had statistically higher total effective rates of treatment; lower overall incidence of adverse events; higher post-treatment E2 levels and L1-4 and bilateral femoral BMD; and lower LH and FSH levels, sleeping time, and frequency of awakenings from sleep after treatment. Therefore, for the treatment of PMS, γ-oryzanol combined with Femoston is significantly better than Femoston alone in terms of clinical effectiveness, exhibiting more pronounced clinical advantages in improving safety, sex hormone levels, BMD, and sleep quality.