Circumventing drug resistance in gastric cancer: A spatial multi-omics exploration of chemo and immuno-therapeutic response dynamics.

BACKGROUND: Gastric Cancer (GC) characteristically exhibits heterogeneous responses to treatment, particularly in relation to immuno plus chemo therapy, necessitating a precision medicine approach. This study is centered around delineating the cellular and molecular underpinnings of drug resistance in this context. METHODS: We undertook a comprehensive multi-omics exploration of postoperative tissues from GC patients undergoing the chemo and immuno-treatment regimen. Concurrently, an image deep learning model was developed to predict treatment responsiveness. RESULTS: Our initial findings associate apical membrane cells with resistance to fluorouracil and oxaliplatin, critical constituents of the therapy. Further investigation into this cell population shed light on substantial interactions with resident macrophages, underscoring the role of intercellular communication in shaping treatment resistance. Subsequent ligand-receptor analysis unveiled specific molecular dialogues, most notably TGFB1-HSPB1 and LTF-S100A14, offering insights into potential signaling pathways implicated in resistance. Our SVM model, incorporating these multi-omics and spatial data, demonstrated significant predictive power, with AUC values of 0.93 and 0.84 in the exploration and validation cohorts respectively. Hence, our results underscore the utility of multi-omics and spatial data in modeling treatment response. CONCLUSION: Our integrative approach, amalgamating mIHC assays, feature extraction, and machine learning, successfully unraveled the complex cellular interplay underlying drug resistance. This robust predictive model may serve as a valuable tool for personalizing therapeutic strategies and enhancing treatment outcomes in gastric cancer.

Diagnosis of Klippel-Trenaunay syndrome and extensive heterotopic ossification in a patient with a femoral fracture: a case report and literature review.

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a rare complex vessel malformation syndrome characterized by venous varicosities, capillary malformations, and limb hypertrophy. However, extensive heterotopic ossification (HO) secondary to this syndrome is extremely rare. CASE PRESENTATION: We report the case of a patient with previously undiagnosed KTS and extensive HO who presented with a femoral fracture secondary to a motor vehicle accident. Extensive ossification, which leads to compulsive contracture deformity and dysfunction of the leg, was distributed on the flexor muscle side, as revealed by the radiograph. The diagnosis was finally established by combining imaging and histological analysis with classical clinical symptoms. Amputation was performed at the fracture site proximal to the infected necrotic foci. Open management of the fracture was challenging owning to the pervasive ossification and tendency for excessive bleeding. Gene sequencing analysis showed homozygous mutation of FoxO1 gene. CONCLUSIONS: Definitive diagnosis of a combination of KTS and extensive HO requires detailed imaging analysis and pathologic evidence. Mutation of the FoxO1 gene, which regulates bone formation by resistance to oxidative stress in osteoblasts, is a potential factor in the microenvironment of malformed vessels caused by KTS.

The Establishment and Verification of a Nomogram Model for Predicting the Overall Survival of Medullary Thyroid Carcinoma: An Analysis Based on the SEER Database.

(1) Background: This study aimed to establish a nomogram model for predicting the overall survival (OS) of medullary thyroid carcinoma (MTC) patients based on the Surveillance, Epidemiology, and End Results (SEER) database. (2) Methods: Patients with MTC in the SEER database from 2004 to 2015 were included and divided into a modeling group and an internal validation group. We also selected MTC patients from our center from 2007 to 2019 to establish an external validation group. Univariate and multivariate Cox regression analyses were used to screen for significant independent variables and to establish a nomogram model. Kaplan-Meier (K-M) curves were plotted to evaluate the influence of the predictors. The C-indexes, areas under the curves (AUCs), and calibration curves were plotted to validate the predictive effect of the model. (3) Results: A total of 1981 MTC patients from the SEER database and 85 MTC patients from our center were included. The univariate and multivariate Cox regression analyses showed that age, tumor size, N stage, and M stage were significant factors, and a nomogram model was established. The C-index of the modeling group was 0.792, and the AUCs were 0.811, 0.825, and 0.824. The C-index of the internal validation group was 0.793, and the AUCs were 0.847, 0.846, and 0.796. The C-index of the external validation group was 0.871, and the AUCs were 0.911 and 0.827. The calibration curves indicated that the prediction ability was reliable. (4) Conclusions: A nomogram model based on age, tumor size, N stage, and M stage was able to predict the OS of MTC patients.

[Comparison of femoral neck system and inverted triangle cannulated screws fixations in treatment of Pauwels typle â ¢ femoral neck fractures].

OBJECTIVE: To compare the effectiveness of the femoral neck system (FNS) and inverted triangle cannulated screws (ITCS) for the treatment of Pauwels type Ⅲ femoral neck fractures. METHODS: The clinical data of 59 patients with Pauwels type Ⅲ femoral neck fractures treated between May 2019 and November 2020 were retrospectively analysed. The patients were divided into FNS group (28 cases) and ITCS group (31 cases) according to the different internal fixation. There was no significant difference in gender, age, affected side, body mass index, cause of injury, smoking history, alcohol abuse history, Pauwels angle, Garden classification, AO/Orthopaedic Trauma Association (AO/OTA) classification, and time from injury to operation between the two groups ( P>0.05). The operation time, incision length, intraoperative blood loss, extra assisted reduction procedures (Kirschner wire prying reduction or open reduction), hospitalization stay, and early complications were recorded and compared between the two groups. Garden index and Haidukewych score were used to evaluate fracture reduction. Fracture healing time, lateral thigh irritation, time of partial or total weight-bearing postoperatively, shortening length and degree of femoral neck, change of caput-collum-diaphysis (CCD) angle (the difference of CCD angle between immediate after operation and last follow-up), incidence of osteonecrosis of femoral head and revision surgery were recorded and compared between the two groups. Hip joint function were evaluated by Harris score. RESULTS: The operation time of FNS group was significantly shorter than ITCS group, and the incision length was significantly longer than ITCS group ( P<0.05). There was no significant difference in intraoperative blood loss, assisted reduction, Garden index, Haidukewych score, and hospitalization stay between the two groups ( P>0.05). All the incisions healed by first intention. There were 2 deep vein thrombosis in the FNS group and 1 pulmonary infection and 1 deep vein thrombosis in the ITCS group. No significant difference was found in the incidence of early postoperative complications (7.1% vs. 6.5%) between the two groups ( P=1.000). Patients in both groups were followed up 3-14 months, and there was no significant difference in follow-up time between the two groups ( t=-0.553, P=0.582). The fracture healing time, Harris score, and the partial weight-bearing time after operation of the FNS group were significantly better than those of the ITCS group ( P<0.05). However, there was no significant difference in total weight-bearing time between the two groups ( Z=-1.298, P=0.194). No lateral thigh irritation was found in the FNS group, while 10 patients in the ITCS group had lateral thigh irritation, and the incidence between the two groups (0 vs. 32.3%) was significant ( P=0.001). At last follow-up, the shortening length and degree of femoral neck and the change of CCD angle in FNS group were significantly less than those in ITCS group ( P<0.05). There was no patient with osteonecrosis of femoral head or reoperation in the FNS group, while 4 patients in the ITCS group underwent reoperation (including 2 cases of osteonecrosis of the femoral head). However, the incidences (0 vs. 6.5%; 0 vs.12.9%) between the two groups were not significant ( P=0.493; P=0.114). CONCLUSION: Using FNS to treat Pauwels type Ⅲ femoral neck fracture is simple as well as able to reduce the shortening of the femoral neck and the change of the CCD angle. Also, FNS is conducive to the recovery of hip joint function, which should be considered as a new choice for the treatment of young femoral neck fracture patients.

Tibial intramedullary nailing in the lateral decubitus position: Technical notes and preliminary clinical outcomes.

BACKGROUND: Traditional intramedullary nailing (IMN) for tibial shaft fractures through an infrapatellar approach is typically performed in the supine position and requires a specially designed operative table and an experienced assistant throughout the surgery. We attempted to perform IMN for tibial fractures in the lateral decubitus position to make the process easier both for surgeons and radiographers. METHODS: A total of 36 tibial IMN procedures were performed with the patient in the lateral position from May 1, 2014 to April 30, 2016. The technical feasibility and early results were evaluated. RESULTS: The mean time to complete the nailing procedure during surgery was 78.4 ±â€Š1.1 min. The mean intraoperative time for fluoroscopy was 36.7 ±â€Š1.1 min. No radiographic angular malalignment or bone non-union was reported. No surgical site infections or other surgery-related complications occurred in our series. CONCLUSION: Tibial IMN through an infrapatellar approach in the lateral decubitus position may be a valuable alternative as it simplifies the procedure for both surgeons and radiographers. This technique is highly effective for surgical operation and fluoroscopy compared to traditional supine position. This technique also seems to provide satisfactory clinical and radiographic outcomes in our preliminary clinical outcomes.

Processing Characteristics of Micro Electrical Discharge Machining for Surface Modification of TiNi Shape Memory Alloys Using a TiC Powder Dielectric.

Titanium-nickel shape memory alloy (SMA) has good biomedical application value as an implant. Alloy corrosion will promote the release of toxic nickel ions and cause allergies and poisoning of cells and tissues. With this background, surface modification of TiNi SMAs using TiC-powder-assisted micro-electrical discharge machining (EDM) was proposed. This aims to explore the effect of the electrical discharge machining (EDM) parameters and TiC powder concentration on the machining properties and surface characteristics of the TiNi SMA. It was found that the material removal rate (MRR), surface roughness, and thickness of the recast layer increased with an increase in the discharge energy. TiC powder's addition had a positive effect on increasing the electro-discharge frequency and MRR, reducing the surface roughness, and the maximum MRR and the minimum surface roughness occurred at a mixed powder concentration of 5 g/L. Moreover, the recast layer had good adhesion and high hardness due to metallurgical bonding. XRD analysis found that the machined surface contains CuO2, TiO2, and TiC phases, contributing to an increase in the surface microhardness from 258.5 to 438.7 HV, which could be beneficial for wear resistance in biomedical orthodontic applications.

IL-1ß promotes osteogenic differentiation of mouse bone marrow mesenchymal stem cells via the BMP/Smad pathway within a certain concentration range.

Inflammatory factors play an important role in the process of fracture healing. The influence of interleukin (IL)-1ß, a key inflammatory factory, on new bone formation has been controversial. The aim of the present study was to investigate whether IL-1ß affects the osteogenic differentiation of mouse bone marrow mesenchymal stem cells (MBMMSCs), and examined its effective concentration range and molecular mechanism of action. MBMMSC proliferation in the presence of IL-1ß was observed using a Cell-Counting Kit-8 assay, and the effect of IL-1ß on MBMMSC apoptosis was examined via flow cytometry. Alkaline phosphatase assay, Alizarin Red staining and quantitative assays were performed to evaluate the osteogenic differentiation of MBMMSCs. The expression levels of osteogenic differentiation markers were detected using reverse transcription-quantitative PCR (RT-qPCR). It was demonstrated that within a concentration range of 0.01-1 ng/ml, IL-1ß promoted osteogenic differentiation of MBMMSCs and did not induce apoptosis. Furthermore, RT-qPCR results indicated that IL-1ß increased osteogenic gene expression within this concentration range. Moreover, Western blotting results identified that the bone morphogenetic protein/Smad (BMP/Smad) signaling pathway was significantly activated by IL-1ß under osteogenic conditions. Therefore, the present results suggested that within a certain concentration range, IL-1ß promoted osteogenic differentiation and function of MBMMSCs via the BMP/Smad signaling pathway.

Combination of a miniplate with tension band wiring for inferior patellar pole avulsion fractures.

BACKGROUND: The tension-band technique, with Kirschner wires or cannulated screws, is one of the most commonly used fixation techniques for patellar fractures. However, it may be not useful for inferior patellar pole fractures as it may lead to fragment reduction loss and fixation failure. We present a surgical technique that combines a miniplate with tension band wiring for inferior patellar pole avulsion fractures and report surgical outcomes. PATIENTS AND METHODS: Between June 2012 and May 2016, 17 consecutive patients (mean age: 51 years) with inferior patellar pole fractures (AO/OTA 34-A1) were treated operatively with a miniature plate in combination with tension band wiring. The final range of motion, bone union time, and Bostman score were the primary outcome measures. RESULTS: The bone union time was 9.5 weeks on average after surgery (range: 8-12 weeks). No patient had loss of reduction or implant failure. There were no cases of irritation or other complications from the implant. At the final follow-up, the average range of motion arc was 128.24° (range: 105-140°). The mean Bostman score at the last follow-up was 28.1 points (range: 25-30 points). All patients showed excellent or good results 1 year after surgery. CONCLUSION: The combination of a miniplate with tension band wiring for inferior patellar pole avulsion fractures provides stable flexion, allows for early range of motion, and provides excellent results in terms of knee function.