• Integrated LC-MS/MS profiling, network pharmacology and experimental validation reveal inhibition of the IL-6/JAK2/STAT3 pathway by Shenqi Compound in comorbid chronic pancreatitis and type 2 diabetes mellitus.
    2 weeks ago
    Shenqi Compound (SQC) is effective in treating type 2 diabetes mellitus (T2DM). Preliminary clinical observations suggest that it may also improve pancreatic fibrosis in T2DM patients with comorbid chronic pancreatitis (CP), which prompted this mechanistic study.

    This study aimed to reveal the multi-component, multi-target, and multi-pathway mechanism of SQC in pancreatic exocrine and endocrine diseases by integrating LC-MS/MS, network pharmacology, molecular docking, molecular dynamics simulation, and in vivo validation.

    Active components and targets of SQC were screened using network pharmacology and LC-MS/MS. Molecular docking and dynamics simulation validated key component target binding. A mouse model of comorbid CP and T2DM was established by feeding a 60% high-fat diet for six weeks, combined with intraperitoneal injection of caerulein (50 μg/kg, six times daily, three days per week, for six weeks) followed by streptozotocin (50 mg/kg daily for five consecutive days). Pancreatic function, histopathology, and protein expression were assessed.

    Network pharmacology identified 145 active components acting on 242 targets, with IL-6, JAK2, and STAT3 as core targets. Quercetin, kaempferol, and luteolin showed good binding to these proteins. The luteolin JAK2 complex remained stable over 100 ns. In animal experiments, SQC improved body weight and food intake, lowered fasting blood glucose, and increased serum glucagon, insulin, lipase, amylase, and fecal elastase 1. SQC also reduced pancreatic IL-6 and TNF-α, alleviated pathological damage and fibrosis, downregulated gp130 and JAK2/STAT3 phosphorylation, and upregulated SOCS3.

    SQC treatment is associated with the suppression of the IL-6/JAK2/STAT3 pathway, accompanied by reduced inflammation, decreased fibrosis, and improvements in both exocrine and endocrine functions in model mice. These findings suggest that the formula potentially acts as a holistic regulator, though the direct causal relationship requires further verification through pathway blockade or genetic ablation.
    Diabetes
    Diabetes type 2
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  • Aggregation kinetics define the temporal window of IAPP proteotoxicity.
    2 weeks ago
    Aggregation of islet amyloid polypeptide (IAPP) to form amyloid contributes to β-cell dysfunction in type 2 diabetes, yet the identity and temporal persistence of the toxic species is unresolved. Competing models attribute toxicity to mature fibrils, fibril growth, or transient prefibrillar intermediates formed during the lag phase or via secondary nucleation. Here, we directly test these models by combining time-resolved β-cell functional assays with concurrent biophysical measurements of IAPP aggregation across multiple perturbations and sequence variants. Across 22 independent experiments spanning more than a 450-fold range in lag times, we find that maximal toxicity occurs during the lag phase and declines as fibrils accumulate. The duration of β-cell dysfunction scales linearly with lag phase length, establishing aggregation kinetics as a quantitative predictor of the onset, peak, and termination of toxicity. Perturbations that alter aggregation kinetics, including concentration, temperature, and sequence, predictably shift the temporal window of toxicity. The diabetes-associated S20G variant produces higher peak toxicity over a compressed time window, whereas the slower-aggregating variants examined prolong toxicity without increasing its magnitude. These results resolve competing models by demonstrating that transient lag-phase intermediates, rather than growth phase processes or mature fibrils, dominate β-cell dysfunction, and establish aggregation kinetics as a predictor of the timing and duration of cellular exposure to toxic intermediates.
    Diabetes
    Diabetes type 2
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  • Assessment of c-Kit immunohistochemical expression in cutaneous basal and squamous cell carcinomas.
    2 weeks ago
    Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most prevalent cutaneous malignancies. C-Kit plays a role in tumor initiation, progress, recurrence, and metastasis. Several medicinal treatments target the c-Kit pathway. The aim of the study was to assess the expression of c-Kit in BCC and cSCC. Furthermore, the study aimed to correlate c-Kit expression with available pathological data of the tumor and clinical data of the patients. A total of 62 excision specimens from patients with BCC (n = 41) and cSCC (n = 21) were histopathologically and immunohistochemically evaluated using anti-c-Kit, a rabbit monoclonal antibody clone IHC526. More than half of BCC cases (63.4%) showed positive c-Kit expression. C-Kit expression was significantly correlated with age (p-value = 0.011). The intensity of positive c-Kit staining was statistically related to tumor size (p-value = 0.028). All cSCC cases (100%) showed negative c-Kit expression. Receiver operating characteristic (ROC) curve analysis demonstrated an area under the curve (AUC) of 0.817 (95% confidence interval: 0.714-0.920, p-value < 0.001), with a sensitivity of 63.4% and a specificity of 100% in differentiating BCC from cSCC. Assessment of c-Kit expression may be beneficial in the diagnosis of BCC and in distinguishing it from cSCC. Its high specificity supports its diagnostic utility; however, due to its moderate sensitivity, it should be interpreted in conjunction with routine histopathological findings. While this study was a diagnostic, it suggested that c-Kit inhibitors may have therapeutic effects in BCC cases that express c-Kit; however, more research is needed to validate this.
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  • Considering the role of shave excision in early melanoma diagnosis.
    2 weeks ago
    Shave excisions are increasingly used in Australian clinical practice for melanoma diagnosis, yet concerns persist regarding margin involvement, diagnostic accuracy and cosmetic outcomes. This study assessed clinician perspectives on the estimated costs, logistics and outcomes of shave versus elliptical excision for melanoma diagnosis.

    An anonymous online survey was distributed to 229 Australian general practitioners and dermatologists involved in skin cancer management. Data on procedure setting, equipment, follow-up, costs and clinical perceptions were analysed.

    Clinicians reported shave excision as faster and less resource-intensive than elliptical excision, with higher rates of same-day procedures and reduced follow-up. Median estimated total cost per procedure was $753 for shave excision versus $1473- $1504 for elliptical excision. Users reported favourable cosmetic outcomes and low incidence of deep margin involvement when performed appropriately.

    Shave excision is likely a cost-saving, diagnostically reliable method for selected lesions. Further prospective research and guideline updates are warranted.
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  • Navigation-Assisted Extra-articular Approach for Curettage of a Subchondral Bone Cyst of the Humeral Trochlea.
    2 weeks ago
    Subchondral bone cysts are intraosseous cystic lesions typically associated with degenerative joint diseases in weight-bearing joints; however, their occurrence in the humeral trochlea is extremely rare. We report a case of a 19-year-old Japanese archer who presented with a 2-year history of right elbow pain. CT revealed an 8- × 4- × 4-mm cystic lesion with partial disruption of the subchondral bone plate on the lateral aspect of the humeral trochlea. As arthroscopic access is technically challenging and intra-articular curettage through the joint surface would damage the cartilage, a navigation-assisted extra-articular approach was selected. A patient-specific three-dimensional surgical plan was designed to achieve cylindrical excision of the lesion and was reconstructed with a β-tricalcium phosphate bone substitute. Postoperative CT scans confirmed complete removal of the cyst. Postoperatively, the patient's elbow pain gradually improved and had completely resolved at 14 months. This case demonstrates that navigation-assisted extra-articular curettage is a feasible technique for treating deep subchondral bone cysts of the humeral trochlea while preserving the articular cartilage.
    Cancer
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  • Multifactorial retrospective analysis of pathological fracture risk and treatment strategies in unicameral bone cysts.
    2 weeks ago
    Unicameral bone cysts (UBCs) are benign fluid-filled bone lesions that primarily affect children and adolescents and carry a clinically relevant risk of pathological fracture. This study explored radiological and clinical variables associated with fracture and recurrence in a histologically confirmed retrospective cohort. Seventy-two patients with histologically confirmed UBCs treated between 2010 and 2021 were retrospectively analysed. Median follow-up was 38 months (range 24-132). Primary outcomes were pathological fracture and radiological recurrence. Because only eight fractures were observed, multivariable analyses were treated as exploratory. Pathological fractures occurred in 8/72 patients (11.1%). Fracture rates were 0/46 (0%), 2/20 (10%) and 6/6 (100%) for Capanna stages 1, 2 and 3, respectively (p < 0.001). Latent cysts had a higher fracture rate than active cysts (21.4% vs 4.5%; p = 0.049). Recurrence occurred in 7/71 evaluable patients (9.9%), exclusively in the interventional group (7/23, 30.4% vs 0/48; p < 0.001). In this retrospective, histologically selected cohort, higher Capanna stage, younger age, latent activity and diaphyseal localisation were associated with fracture risk. Given the limited number of fracture events, the mixed paediatric-adult population and the selection bias inherent to histological inclusion, these findings are best interpreted as exploratory and hypothesis-generating. Overall, they may be more compatible with structured, individualised risk assessment than with a prescriptive Capanna-guided treatment algorithm.
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  • Custom 3D Implant for Hemiarthroplasty of the Third Metacarpal in a Giant Cell Tumor of bone: Functional Outcomes and Hand Stability.
    2 weeks ago
    Giant cell tumor (GCT) of the hand is a rare benign but locally aggressive bone tumor with high recurrence rates. It is commonly treated by curettage with cementation or bone grafting. However, reconstruction after en bloc resection of metacarpal GCT remains challenging, particularly in young patients. Conventional options such as allografts or standard prostheses are associated with notable complications and functional limitations. Custom- made 3D-printed implants have recently emerged as a potential alternative, although current evidence is limited. We report the case of a 19-year-old woman with a recurrent GCT of the third metacarpal following initial curettage and cementation. After neoadjuvant denosumab therapy, an en bloc resection of the third metacarpal was performed. Reconstruction was achieved using a patient-specific 3D-printed titanium hemiarthroplasty featuring an intramedullary stem, screw fixation, porous surfaces for osseointegration, and dedicated structures for ligament reinsertion to ensure hand stability. Early postoperative mobilization was allowed. At mid-term follow-up, the patient demonstrated excellent functional recovery, high total active motion, minimal pain, and no complications, implant instability, or tumor recurrence. Custom-made metacarpal hemiarthroplasty appears particularly suitable for reconstruction of central rays, where transverse stability is supported by adjacent structures. This case supports patient-specific 3D-printed hemiarthroplasty as a promising reconstructive option, providing favorable early functional outcomes while preserving joint biomechanics. Further studies are needed to assess long-term durability.
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  • Outcomes of hemicortical resection and reconstruction with liquid nitrogen-treated autograft for high-grade sarcomas: A retrospective case series.
    2 weeks ago
    Hemicortical resection (HCR) is a limb salvage option for eccentrically located bone sarcomas that allows preservation of native bone stock and nearby joint anatomy. Evidence on outcomes in high-grade extremity sarcomas remains limited. We performed a retrospective case series of consecutive patients undergoing HCR for high-grade primary malignant bone tumors of the extremities. Collected variables included demographics, tumor type and location, systemic therapy, local radiotherapy, radiographic union, time to union, complications, local recurrence, distant metastasis, survival status, and last follow-up. Five patients were included (mean age 14.2 years; 3/5 female). Diagnoses were Ewing sarcoma (n = 3) and osteosarcoma (n = 2). Sites were distal femur (n = 2), proximal tibia (n = 1), distal tibia (n = 1), and tibial shaft (n = 1). One patient received local radiotherapy. Union was achieved in all cases. Median time to union was 8.2 months (mean 11.1; range 4.4-18.9). Median follow-up was 20.8 months (mean 19.3; range 11.7-23.4). Complications included one infection treated with antibiotics and one late implant exposure requiring debridement and flap coverage. No local recurrences, distant metastases, or deaths were observed at last follow-up. In this small series, HCR with biological reconstruction achieved universal union and a low early complication rate. No local recurrence, distant metastasis, or death was observed during the available follow-up; however, oncologic safety cannot be inferred from this limited cohort, and larger studies with longer follow-up are required. INTRODUCTION tumor-bearing autograft devitalized by methods such as liquid nitrogen (LN), pasteurization, irradiation, 5-7 Limb salvage surgery has become the standard of care or ethanol . Among these, LN-treated autograft is for most localized high-grade extremity sarcomas widely used because it delivers rapid, deep cytocidal when wide margins are achievable and function can temperatures while p.
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  • Fibulectomy for primary fibular tumors A Decade of experience at the National Cancer Institute, Egypt.
    2 weeks ago
    Primary fibular tumors, whether benign or malignant, are uncommon and include entities such as osteochondroma, giant cell tumor, aneurysmal bone cyst, Ewing sarcoma, and osteosarcoma. Optimal management depends on careful radiological assessment to guide precise surgical planning and achieve adequate oncological outcomes. This study assessed surgical technique with post-treatment sequelea and survival analysis for fibular tumors. This retrospective study analyzed 22 patients with primary fibular tumors who underwent surgical resection at the National Cancer Institute, Cairo University, Egypt, between January 2013 and January 2023, evaluating clinical characteristics, treatment modalities, surgical techniques, postoperative sequelae, and survival outcomes. All patients presented with leg swelling, and the proximal fibula was the most frequently involved site (81.8%), followed by the distal fibula and diaphysis (each 9.1%). Osteosarcoma was the most common histopathological diagnosis (40.9%), followed by Ewing sarcoma (27.3%), giant cell tumor (22.7%), and chondrosarcoma (9.1%). Neoadjuvant therapy was administered in 68.2% of cases. Surgical management included proximal fibulectomy in 36.4% of patients, segmental resection in 27.3%, and above-knee amputation in 13.6%, with preservation of the common peroneal nerve achieved in 68.2% of patients. With a median follow-up of 32 months, the overall recurrence rate was 50%, including 22.7% among osteosarcoma cases. Overall survival rates at one, two, and three years were 94.4%, 75.4%, and 50.2%, respectively, while event-free survival rates at one, two, and three years were 79.4%, 56.3%, and 42.9%. The fibula presents unique surgical challenges due to its anatomical relationship with critical neurovascular structures, particularly the common peroneal nerve, and its contribution to knee and ankle stability; therefore, meticulous preoperative planning and appropriate surgical techniques are essential to achieve safe tumor res.
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  • Use of Information and Communication Technologies in Patients With Cancer Receiving Antineoplastic or Supportive Therapy: Comparative Cross-Sectional Survey.
    2 weeks ago
    The expansion of information and communication technologies (ICTs) has transformed the way patients access health information and manage their disease. In oncology and hematology care, the use of digital tools and mobile health has increased, especially after the COVID-19 pandemic, although challenges remain regarding adoption, trust, and perceived utility.

    This study aimed to evaluate the current use of ICTs by patients with cancer receiving antineoplastic and/or supportive therapy, to assess their interest in mobile apps for disease management, and to compare these findings with those obtained in a previous survey conducted in 2017.

    A comparative cross-sectional survey was conducted in a 1300-bed university hospital between August and December 2023. Adult patients with solid tumors or hematological malignancies receiving antineoplastic and/or supportive therapy were invited to complete a structured paper questionnaire based on a previous survey conducted in 2017. The questionnaire included 30 items regarding sociodemographic and clinical characteristics, ICT use, preferences concerning health apps, and the impact of the COVID-19 pandemic. Descriptive and inferential analyses were performed to compare results between the prepandemic survey conducted in 2017 (2017 study group; n=612) and the postpandemic survey conducted in 2023 (2023 study group; n=690). Missing responses were reported as "no response" and were not imputed.

    Smartphone use increased from 82.5% (505/612) to 91% (628/690; P<.001), and the proportion of patients with installed health apps rose from 20.3% (124/612) to 53.9% (372/690; P<.001). Familiarity with technological terms and the use of connected devices also improved. However, full trust in online health information remained low (64/690, 9.3%), with most patients reporting trust contingent on source credibility. Preference for videoconferencing as a communication channel with health care professionals increased from 19% (116/612) to 32% (221/690; P<.001), while the use of email and mobile apps for this purpose declined. Willingness to use apps recommended by health care professionals remained high, although it decreased slightly from 81.4% (498/612) to 77.8% (537/690).

    The use of ICTs and digital health tools among patients with cancer has increased significantly in recent years, particularly after the COVID-19 pandemic. Nevertheless, barriers persist in terms of source credibility, usability, digital skills, and alignment with patient preferences. Strategies such as clinician-curated information sources, co-designed apps, simple communication channels, and targeted digital literacy support may help integrate these technologies more effectively and equitably in cancer care.
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