Coal power activities could cause regional fluctuations of trace elements, but the distribution information of these trace elements in arid and semi-arid areas is insufficient. In this study, the soil trace elements (As, B, Be, Cd, Co, Cr, Cu, Fe, Ga, Ge, Mn, Mo, Ni, Pb, Sb, Sn, Sr, Ti, Tl, and Zn) of Ningdong Coal Power Production Base in China were monitored. Results showed that the concentrations of B, Tl, Mn, Pb, Cr, K, Cu, and Co exceeded background values. The maximum risk index reached 265.66, while the trace elements posed a cancer risk to children. Combining correlation analyses (CA), principal component analysis (PCA), and positive matrix factorization (PMF) techniques, it indicated that trace elements were mainly coming from coal combustion (34.15%), livestock farming (17.44%), traffic emissions (12.42%), and natural factors (35.99%). This study reveals the sources and potential ecological risks of soil trace elements in the Ningdong Coal and Power Production Base. It provides a scientific basis for developing targeted environmental management measures and reducing human health risks.
Coal , Environmental Monitoring , Soil Pollutants , Soil , Trace Elements , China , Trace Elements/analysis , Soil Pollutants/analysis , Soil/chemistry , Power Plants , Humans
OBJECTIVE: Management of extensive acetabular bone defects in total hip arthroplasty (THA) remains challenging. This study aims to investigate the feasibility and preliminary outcomes of 3D-printed personalized porous acetabular components for the reconstruction of acetabular defects in primary THA. METHODS: This retrospective study involved seven patients who received 3D-printed acetabular components in primary THA between July 2018 and March 2021. Preoperatively, acetabular bone defects were evaluated by referencing the Paprosky classification. There were two "Paprosky type IIIA" defects and five "Paprosky type IIIB" defects. The acetabular components were custom-made for each patient to reconstruct the extensive acetabular defects. The hip function was assessed according to the Harris hip score (HHS). Clinical and radiographic outcomes were assessed. RESULTS: The average follow-up period was 40 months, ranging from 26 to 57 months. There were no patients lost to follow-up. The HHS improved from 44 (range: 33-53) before the operation to 88 (range: 79-93) at the final follow-up. Postoperative X-rays showed that the 3D-printed personalized components were properly fitted with the acetabulum. The average center of rotation (COR) discrepancy was 2.3 mm horizontally and 2.1 mm vertically, respectively. Tomosynthesis-Shimadzu metal artifact reduction technology images showed that the implant was in close contact with the host bone. Moreover, no complications were observed during the follow-up period, including loosening, dislocation, or component protrusion. CONCLUSION: The implantation of 3D-printed personalized acetabular components showed accurate reconstruction, stable mechanical support, and favorable function at short-term follow-up. This may be a viable alternative method for reconstructing extensive acetabular defects in THA.
Objective: Little is known about the association between whole-blood nicotinamide adenine dinucleotide (NAD +) levels and nabothian cysts. This study aimed to assess the association between NAD + levels and nabothian cysts in healthy Chinese women. Methods: Multivariate logistic regression analysis was performed to analyze the association between NAD + levels and nabothian cysts. Results: The mean age was 43.0 ± 11.5 years, and the mean level of NAD + was 31.3 ± 5.3 µmol/L. Nabothian cysts occurred in 184 (27.7%) participants, with single and multiple cysts in 100 (15.0%) and 84 (12.6%) participants, respectively. The total nabothian cyst prevalence gradually decreased from 37.4% to 21.6% from Q1 to Q4 of NAD + and the prevalence of single and multiple nabothian cysts also decreased across the NAD + quartiles. As compared with the highest NAD + quartile (≥ 34.4 µmol/L), the adjusted odds ratios with 95% confidence interval of the NAD + Q1 was 1.89 (1.14-3.14) for total nabothian cysts. The risk of total and single nabothian cysts linearly decreased with increasing NAD + levels, while the risk of multiple nabothian cysts decreased more rapidly at NAD + levels of 28.0 to 35.0 µmol/L. Conclusion: Low NAD + levels were associated with an increased risk of total and multiple nabothian cysts.
NAD , Humans , Female , Adult , Middle Aged , NAD/blood , NAD/metabolism , Cysts/blood , Cysts/epidemiology , China/epidemiology
Gastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi-regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking-associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra-patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra-patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD-L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis-to-metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland.
Stroke is a major threat to life and health in modern society, especially in the aging population. Stroke may cause sudden death or severe sequela-like hemiplegia. Although computed tomography (CT) and magnetic resonance imaging (MRI) are standard diagnosis methods, and artificial intelligence models have been built based on these images, shortage in medical resources and the time and cost of CT/MRI imaging hamper fast detection, thus increasing the severity of stroke. Here, we developed a convolutional neural network model by integrating four networks, Xception, ResNet50, VGG19, and EfficientNetb1, to recognize stroke based on 2D facial images with a cross-validation area under curve (AUC) of 0.91 within the training set of 185 acute ischemic stroke patients and 551 age- and sex-matched controls, and AUC of 0.82 in an independent data set regardless of age and sex. The model computed stroke probability was quantitatively associated with facial features, various clinical parameters of blood clotting indicators and leukocyte counts, and, more importantly, stroke incidence in the near future. Our real-time facial image artificial intelligence model can be used to rapidly screen and prediagnose stroke before CT scanning, thus meeting the urgent need in emergency clinics, potentially translatable to routine monitoring.
KRAS is frequently mutated in cancer, contributing to 20% of all human cancer especially pancreatic, colorectal and lung cancer. Signaling of the constitutively active KRAS oncogenic mutants is mostly compartmentalized to proteolipid nanoclusters on the plasma membrane (PM). Signaling nanoclusters of many KRAS mutants selectively enrich phosphatidylserine (PS) lipids with unsaturated sn-2 acyl chains, but not the fully saturated PS species. Thus, remodeling PS acyl chains may suppress KRAS oncogenesis. Lysophosphatidylcholine acyltransferases (LPCATs) remodel sn-2 acyl chains of phospholipids, with LPCAT1 preferentially generating the fully saturated lipids. Here, we show that stable expression of LPCAT1 depletes major PS species with unsaturated sn-2 chains while decreasing minor phosphatidylcholine (PC) species with the corresponding acyl chains. LPCAT1 expression more effectively disrupts the nanoclustering of oncogenic GFP-KRAS G12V , which is restored by acute addback of exogenous unsaturated PS. LPCAT1 expression compromises signaling and oncogenic activities of the KRAS-dependent pancreatic tumor lines. LPCAT1 expression sensitizes human pancreatic tumor MiaPaCa-2 cells to KRAS G12C specific inhibitor, Sotorasib. Statistical analyses of patient data further reveal that pancreatic cancer patients with KRAS mutations express less LPCAT1. Higher LPCAT1 expression also improves survival probability of pancreatic and lung adenocarcinoma patients with KRAS mutations. Thus, PS acyl chain remodeling selectively suppresses KRAS oncogenesis.
PURPOSE: The spinopelvic reconstruction poses significant challenges following total sacrectomy in patients with malignant or aggressive benign bone tumours encompassing the entire sacrum. In this study, we aim to assess the functional outcomes and complications of an integrated 3D-printed sacral endoprostheses featuring a self-stabilizing design, eliminating the requirement for supplemental fixation. METHODS: We retrospectively analyzed patients with sacral tumours who underwent total sacrectomy followed by reconstruction with 3D-printed self-stabilizing endoprosthesis. Clinically, we evaluated functional outcomes using the 1993 version of the musculoskeletal tumour society (MSTS-93) score. Perioperative and postoperative complications were also documented. RESULTS: 10 patients met final inclusion criteria. The median age was 49 years (range, 31-64 years). The median follow-up time was 26.5 months (range, 15-47 months). Median postoperative functional MSTS-93 was 22.5 (range, 13-25). The median operation time was 399.5 min (305-576 min), and the median intraoperative blood loss was and 3200 ml (2400-7800 ml). Complications include wound dehiscence in one patient, bowel, bladder, and sexual dysfunction in four patients, cerebrospinal fluid leak in one patient, and tumour recurrence in one patient. There were no mechanical complications related to the endoprosthesis at the last follow-up. CONCLUSION: The utilization of 3D-printed self-stabilizing endoprosthesis proved to be a viable approach, yielding satisfactory short-term outcomes in patients undergoing total sacral reconstruction without supplemental fixation.
Recombinant human erythropoietin (rhEPO) is a glycoprotein that acts as the main hormone involved in regulating red blood cell production to treat anemia caused by chronic kidney disease or chemotherapy, which has three N-glycosylation sites and one O-glycosylation site. It contains a variety of different glycosylation modifications, such as sialyation, O-acetylation on sialic acids, etc., which causes a big challenge for the glycosylation analysis of rhEPO. In this study, a liquid chromatography-mass spectrometry (LC-MS) method combined with electron-activated dissociation (EAD) technology was used in qualitative and quantitative characterization of rhEPO N-glycosylation and O-glycosylation in just one injection. The usage of EAD not only generated abundant MS/MS fragment ions of glycopeptides and improved the MS/MS sequence coverage but also preserved the glycan structures in the MS/MS fragment ions and the integrity of the glycosidic bond between the glycans and peptides. Three N-glycosylation sites (N24, N38, and N83) and one O-glycosylation site (S126) of rhEPO samples were successfully identified. Among them, the glycosylation ratios of N24, N38, and N83 sites were 82.7%, 100%, and 100% respectively, and 15, 10, and 12 different N-glycans could be identified at the glycopeptide level. The total average number of sialic acids, N-hydroxyacetylneuraminoic acid, and O-acetylation on sialic acid were 7.28, 4.21, and 0.66 at the intact protein level, respectively. For O-glycosylation site S126, O-glycosylation ratios analyzed at the intact protein level and the glycopeptide level were 80.2% and 80.3%, respectively, and two O-glycans were identified, including Core1_S1 and Core1_S2. This study also compared the difference of the glycans and their relative contents in batch-to-batch rhEPO samples. The results proved that the workflow using EAD fragmentation in LC-MS method could be effectively applied for characterizing the glycosylation analysis of rhEPO samples and batch-to-batch consistency analysis, which would help to reasonably guide the optimization of rhEPO production process.
Background: In the context of surgical interventions for lung adenocarcinoma (LADC), precise determination of the extent of LADC infiltration plays a pivotal role in shaping the surgeon's strategic approach to the procedure. The prevailing diagnostic standard involves the expeditious intraoperative pathological diagnosis of areas infiltrated by LADC. Nevertheless, current methodologies rely on the visual interpretation of tissue images by proficient pathologists, introducing an error margin of up to 15.6%. Methods: In this study, we investigated the utilization of Micro-Raman technique on isolated specimens of human LADC with the objective of formulating and validating a workflow for the pathological diagnosis of LADC featuring diverse degrees of infiltration. Our strategy encompasses a thorough pathological characterization of LADC, spanning different tissue types and levels of infiltration. Through the integration of Raman spectroscopy with advanced deep learning models for simultaneous diagnosis, this approach offers a swift, precise, and clinically relevant means of analysis. Results: The diagnostic performance of the convolutional neural network (CNN) model, coupled with the microscopic Raman technique, was found to be exceptional and consistent, surpassing the traditional support vector machine (SVM) model. The CNN model exhibited an area under the curve (AUC) value of 96.1% for effectively distinguishing normal tissue from LADC and an impressive 99.0% for discerning varying degrees of infiltration in LADCs. To comprehensively assess its clinical utility, Raman datasets from patients with intraoperative rapid pathologic diagnostic errors were utilized as test subjects and input into the established CNN model. The results underscored the substantial corrective capacity of the Micro-Raman technique, revealing a misdiagnosis correction rate exceeding 96% in all cases. Conclusions: Ultimately, our discoveries highlight the Micro-Raman technique's potential to augment the intraoperative diagnostic precision of LADC with varying levels of infiltration. And compared to the traditional SVM model, the CNN model has better generalization ability in diagnosing different infiltration levels. This method furnishes surgeons with an objective groundwork for making well-informed decisions concerning subsequent surgical plans.
The globally prevalent pests, Diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae) and Beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae), pose significant threats to cruciferous vegetables. They have rapidly developed resistance to a wide range of insecticides, leading to significant yield losses and increased control expenses. In this study, we have established an efficient approach utilizing amplicon sequencing to detect the frequency of 15 target resistance mutant sites in 6 molecular targets, acetylcholinesterase 1 (ACE1), chitin synthase 1 (CHS1), the γ-aminobutyric acid receptor (GABAR), glutamate-gated chloride channel (GluCl), voltage-gated sodium channels (NaV), and ryanodine receptor (RyR) in P. xylostella and the frequency of 11 mutations in 5 molecular targets (except GluCl) in S. exigua in China. Our findings indicate that P. xylostella exhibits remarkably high frequency (over 88.67%) in pyrethroid resistance-related mutations T929I and L1014F of NaV. In S. exigua, the frequencies of L659F mutation were ranging from 41.92% to 74.89%. In addition, the organophosphorus resistance-related mutations A298S and G324A of ACE1 were detected at frequencies ranging from 34.29% to 75.66%, and these 2 mutations occurred simultaneously (from 29.22% to 65.79%) in P. xylostella. An interannual variation in mutation frequency from 2019 to 2021 was found for P. xylostella in HNCS. The frequency of A298S and G324A mutations steadily increased while the frequency of G4946E and I4790M mutations continuously decreased. These results unveil a worrisome scenario of multiple resistance sites in these 2 pests in China and provide valuable insights for the practical application of pesticides in the field.
PURPOSE: Resection of pelvic bone tumours and subsequent pelvic girdle reconstruction pose formidable challenges due to the intricate anatomy, weight-bearing demands, and significant defects. 3D-printed implants have improved pelvic girdle reconstruction by enabling precise resections with customized guides, offering tailored solutions for diverse bone defect morphology, and integrating porous surface structures to promote osseointegration. Our study aims to evaluate the long-term efficacy and feasibility of 3D-printed hemipelvic reconstruction following resection of malignant pelvic tumours. METHODS: A retrospective review was conducted on 96 patients with primary pelvic malignancies who underwent pelvic girdle reconstruction using 3D-printed custom hemipelvic endoprostheses between January 2017 and May 2022. Follow-up duration was median 48.1 ± 17.9 months (range, 6 to 76 months). Demographic data, imaging examinations, surgical outcomes, and oncological evaluations were extracted and analyzed. The primary endpoints included oncological outcomes and functional status assessed by the Musculoskeletal Tumor Society (MSTS-93) score. Secondary endpoints comprised surgical duration, intraoperative bleeding, pain control and complications. RESULTS: In 96 patients, 70 patients (72.9%) remained disease-free, 15 (15.6%) had local recurrence, and 11 (11.4%) succumbed to metastatic disease. Postoperatively, function improved with MSTS-93 score increasing from 12.2 ± 2.0 to 23.8 ± 3.8. The mean operating time was 275.1 ± 94.0 min, and the mean intraoperative blood loss was 1896.9 ± 801.1 ml. Pain was well-managed, resulting in substantial improvements in VAS score (5.3 ± 1.8 to 1.4 ± 1.1). Complications occurred in 13 patients (13.5%), including poor wound healing (6.3%), deep prosthesis infection (4.2%), hip dislocation (2.1%), screw fracture (1.0%), and interface loosening (1.0%). Additionally, all patients achieved precise implantation of customized prosthetics according to preoperative plans. T-SMART revealed excellent integration at the prosthesis-bone interface for all patients. CONCLUSION: The use of a 3D-printed custom hemipelvic endoprosthesis, characterized by anatomically designed contours and a porous biomimetic surface structure, offers a potential option for pelvic girdle reconstruction following internal hemipelvectomy in primary pelvic tumor treatment. Initial results demonstrate stable fixation and satisfactory mid-term functional and radiographic outcomes.
Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term in vivo gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and High Sedimentation Coefficient Substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF( high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the RSD (relative standard deviation) could be within 5%. Even for empty or partial less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4×1011 cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Due to the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control)laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with hyperlipidemia, which is closely related to high levels of sugar and fat. ß-sitosterol is a natural product with significant hypolipidemic and cholesterol-lowering effects. However, the underlying mechanism of its action on aquatic products is not completely understood. METHODS: A high-fat diet (HFD)-induced NAFLD zebrafish model was successfully established, and the anti-hyperlipidemic effect and potential mechanism of ß-sitosterol were studied using oil red O staining, filipin staining, and lipid metabolomics. RESULTS: ß-sitosterol significantly reduced the accumulation of triglyceride, glucose, and cholesterol in the zebrafish model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differential lipid molecules in ß-sitosterol mainly regulated the lipid metabolism and signal transduction function of the zebrafish model. ß-sitosterol mainly affected steroid biosynthesis and steroid hormone biosynthesis in the zebrafish model. Compared with the HFD group, the addition of 500 mg/100 g of ß-sitosterol significantly inhibited the expression of Ppar-γ and Rxr-α in the zebrafish model by at least 50% and 25%, respectively. CONCLUSIONS: ß-sitosterol can reduce lipid accumulation in the zebrafish model of NAFLD by regulating lipid metabolism and signal transduction and inhibiting adipogenesis and lipid storage.
Purpose: The complicated pathogenesis and poor prognosis of breast cancer have become a major difficulty in medical research. This study aims to explore new lncRNA as prognostic markers for breast cancer and explore their roles and molecular mechanisms to lay a foundation for the treatment of cancer patients. Patients and Methods: The expression of LINC02418 and miR-766-5p in breast cancer tissues and cells was first identified using polymerase chain reaction, and Pearson was used to examine the correlation between the two. The cancer cells activities under different transfection conditions were detected using the Transwell assay and CCK8 assay. The correlation between LINC02418 and patient prognosis was analyzed using multifactor Cox regression and Kaplan-Meier. Results: It was shown that LINC02418 expression was upregulated in breast cancer tissues and cells. There are significant differences in lymph node metastasis and TNM stage between high and low LINC02418 expression groups. The higher the expression of LINC02418, the higher the mortality rate of breast cancer patients. miR-766-5p expression was downregulated and negatively correlated with LINC02418. There are binding sites between LINC02418 and miR-766-5p; Transfection with miR-766-5p inhibitor boosted LINC02418 luciferase activity, but transfection with miR-766-5p mimic decreased it. Knockdown of LINC02418 promoted miR-766-5p expression and inhibited cancer progression, which was alleviated to some extent by transfection with miR-766-5p inhibitors. Conclusion: LINC02418 has the potential to serve as a poor prognostic marker for breast cancer and plays a pro-oncogenic role by targeting miR-766-5p.
OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.
BACKGROUND: Talar malignant tumor is extremely rare. Currently, there are several alternative management options for talus malignant tumor including below-knee amputation, tibio-calcaneal arthrodesis, and homogenous bone transplant while their shortcomings limited the clinical application. Three-dimensional (3D) printed total talus prosthesis in talus lesion was reported as a useful method to reconstruct talus, however, most researches are case reports and its clinical effect remains unclear. Therefore, the current study was to explore the application of 3D printed custom-made modular prosthesis in talus malignant tumor. METHODS: We retrospectively analyzed the patients who received the 3D printed custom-made modular prosthesis treatment due to talus malignant tumor in our hospital from February 2016 to December 2021. The patient's clinical data such as oncology outcome, operation time, and volume of blood loss were recorded. The limb function was evaluated with the Musculoskeletal Tumor Society 93 (MSTS-93) score, The American Orthopedic Foot and Ankle Society (AOFAS) score; the ankle joint ranges of motion as well as the leg length discrepancy were evaluated. Plain radiography and Tomosynthesis-Shimadzu Metal Artefact Reduction Technology (T-SMART) were used to evaluate the position of prosthesis and the osseointegration. Postoperative complications were recorded. RESULTS: The average patients' age and the follow-up period were respectively 31.5 ± 13.1 years; and 54.8 months (range 26-72). The medium operation time was 2.4 ± 0.5 h; the intraoperative blood loss was 131.7 ± 121.4 ml. The mean MSTS-93 and AOFAS score was 26.8 and 88.5 respectively. The average plantar flexion, dorsiflexion, varus, and valgus were 32.5, 9.2, 10.8, and 5.8 degree respectively. One patient had delayed postoperative wound healing. There was no leg length discrepancy observed in any patient and good osseointegration was observed on the interface between the bone and talus prosthesis in all subjects. CONCLUSION: The modular structure of the prosthesis developed in this study seems to be convenient for prosthesis implantation and screws distribution. And the combination of solid and porous structure improves the initial stability and promotes bone integration. Therefore, 3D printed custom-made modular talus prosthesis could be an alternative option for talus reconstruction in talus malignant tumor patients.
Bone Neoplasms , Printing, Three-Dimensional , Prosthesis Design , Talus , Humans , Talus/surgery , Talus/diagnostic imaging , Male , Adult , Female , Bone Neoplasms/surgery , Bone Neoplasms/diagnostic imaging , Retrospective Studies , Middle Aged , Young Adult , Prosthesis Implantation/methods , Prosthesis Implantation/instrumentation , Adolescent , Ankle Joint/surgery , Ankle Joint/diagnostic imaging , Osseointegration , Treatment Outcome , Range of Motion, Articular , Prostheses and Implants
Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.
Introduction: Desmoid fibromatosis is an aggressive fibroblastic neoplasm with a high propensity for local recurrence. Targeted therapy for Desmoid fibromatosis represents a novel avenue in systemic treatment. Anlotinib, a novel multitargeted angiogenesis inhibitor, represents a novel approach for targeted therapy. Therefore, this study aims to assess the efficacy and safety of anlotinib in patients with Desmoid fibromatosis. Methods: We retrospectively gathered the clinical medical records of Desmoid fibromatosis patients who underwent anlotinib treatment between June 2019 and November 2023 at our center. Anlotinib was initiated at a daily dose of 12 mg and adjusted based on drug-related toxicity. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Progression-free survival served as the primary endpoint and was analyzed utilizing the Kaplan-Meier method. Results: In total, sixty-six consecutive patients were enrolled. No patients achieved a complete response; however, fourteen patients (21.21%) exhibited a partial response, while forty-six patients (70%) experienced disease stability. Progressive disease was observed in 6 patients (9.10%), and the progression-free survival rates at 12 and 36months were 89.71% and 82.81%, respectively. The disease control rate was 90.91%, while the objective response rate was 21.21%. Conclusion: Anlotinib proves effective in managing recurrent and symptomatic patients with Desmoid fibromatosis. However, the toxicity profile of anlotinib presents a higher risk of Hand-Foot Skin Reaction and hypertension. Therefore, given that 41.67% of patients were subjected to dose adjustments associated with the initial dose of 12 mg, implementing dosage reductions may help balance efficacy with side effects.
Introduction: Biliary Infection in patients is a common and important phenomenon resulting in severe complications and high morbidity, while the distributions and drug resistance profiles of biliary bacteria and related risk factors are dynamic. This study explored the characteristics of and risk factors for biliary infection to promote the rational use of antibiotics in clinically. Methods: Bacterial identification and drug susceptibility testing were completed using the Vitek 2 Compact analysis system. The distribution and antibiotic-resistant characteristics of 3,490 strains of biliary bacteria in patients at Nankai Hospital from 2019 to 2021 were analyzed using Whonet 5.6 and SPSS 26.0 software. We then retrospectively analyzed the clinical data and risk factors associated with 2,340 strains of Gram-negative bacilli, which were divided into multidrug-resistant bacteria (1,508 cases) and non-multidrug-resistant bacteria (832 cases) by a multivariate Cox regression model. Results and discussion: A total of 3,490 pathogenic bacterial strains were isolated from bile samples, including 2,340 (67.05%) Gram-negative strains, 1,029 (29.48%) Gram-positive strains, and 109 (4.56%) fungal strains. The top five pathogenic bacteria were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, Enterococcus faecalis, and Pseudomonas aeruginosa. The rate of Escherichia coli resistance to ciprofloxacin increased (p < 0.05), while the resistance to amikacin decreased (p < 0.05). The resistance of Klebsiella pneumoniae to cephalosporins, carbapenems, ß-lactamase inhibitors, cephalases, aminoglycosides, and quinolones increased (p < 0.05), and the resistance of Pseudomonas aeruginosa to piperacillin, piperacillin/tazobactam, ticacillin/clavulanic acid, and amicacin declined significantly (p < 0.05). The resistance of Enterococcus faecium to tetracycline increased by year (p < 0.05), and the resistance of Enterococcus faecalis to erythromycin and high-concentration gentamicin declined (p < 0.05). Multivariate logistic regression analysis suggested that the administration of third- or fourth-generation cephalosporins was an independent risk factor for biliary infection. In summary, Gram-negative bacilli were the most common pathogenic bacteria isolated from biliary infection patients, especially Escherichia coli, and the rates and patterns of drug resistance were high and in constant flux; therefore, rational antimicrobial drug use should be carried out considering risk factors.
Background: The cartilage stem/progenitor cells (CSPC) play a critical role in maintaining cartilage homeostasis. However, the effects of phenotypic fluctuations of CSPC on cartilage degeneration and the role of CSPC in the pathogenesis of OA is largely unknown. Methods: The cartilage samples of 3 non-OA and 10 OA patients were collected. Human CSPC (hCSPC) derived from these patients were isolated, identified, and evaluated for cellular functions. Additionally, chondrocytes derived from OA patients were isolated. The effect of Yes-associated protein (YAP) expression on hCSPC was investigated in vitro. The OA rat model was established by Hulth's method. Lentivirus-mediated YAP (Lv-YAP) or lentivirus-mediated YAP RNAi (Lv-YAP-RNAi) was injected intra-articularly to modulate YAP expression in rat joints. In addition, allogeneic rat CSPC (rCSPC) overexpressing or silencing YAP were transplanted by intra-articularly injection. We also evaluated the functions of rCSPC and the OA-related cartilage phenotype in the rat model. Finally, the transcriptome of OA rCSPC overexpressing YAP was examined to explore the potential downstream targets of YAP in rCSPC. Results: hCSPC derived from OA patients exhibited differential chondrogenesis capacity. Among them, a subset of hCSPC showed pronounced dysfunction, including impaired chondrogenic differentiation, inhibition of proliferation and migration, and downregulation of lubricin. Additionally, YAP was lowly expressed in quiescent non-OA hCSPC, upregulated in activated OA hCSPC, but significantly downregulated in dysfunctional OA hCSPC. Notably, the overexpression of YAP in OA hCSPC improved the proliferation, lubricin production, cell migration, and senescence, while silencing YAP had the opposite effect. In vivo, upregulation of YAP in the joint delayed OA progression and improved the cartilage regeneration capacity of rCSPC. Using transcriptomic analysis, we found that YAP may regulate rCSPC function by upregulating Baculoviral IAP repeat-containing 2 (BIRC2). Importantly, the knockdown of BIRC2 partly blocked the regulation of YAP on the CSPC function. Conclusion: Dysfunction of CSPC compromises the intrinsic repair capacity of cartilage and impairs cartilage homeostasis in OA. Notably, the transcriptional co-activator YAP plays a critical role in maintaining CSPC function through potential target gene BIRC2. The Translational Potential of this Article: In this study, we observed targeting the YAP-BIRC2 axis improved the CSPC function and restored the cartilage homeostasis in OA. This study provides a potential stem cell-modifying OA therapy.
