The use of longitudinal CT-based radiomics and clinicopathological features predicts the pathological complete response of metastasized axillary lymph nodes in breast cancer.

BACKGROUND: Accurate assessment of axillary status after neoadjuvant therapy for breast cancer patients with axillary lymph node metastasis is important for the selection of appropriate subsequent axillary treatment decisions. Our objectives were to accurately predict whether the breast cancer patients with axillary lymph node metastases could achieve axillary pathological complete response (pCR). METHODS: We collected imaging data to extract longitudinal CT image features before and after neoadjuvant chemotherapy (NAC), analyzed the correlation between radiomics and clinicopathological features, and developed models to predict whether patients with axillary lymph node metastasis can achieve axillary pCR after NAC. The clinical utility of the models was determined via decision curve analysis (DCA). Subgroup analyses were also performed. Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS: A total of 549 breast cancer patients with metastasized axillary lymph nodes were enrolled in this study. 42 independent radiomics features were selected from LASSO regression to construct a logistic regression model with clinicopathological features (LR radiomics-clinical combined model). The AUC of the LR radiomics-clinical combined model prediction performance was 0.861 in the training set and 0.891 in the testing set. For the HR + /HER2 - , HER2 + , and Triple negative subtype, the LR radiomics-clinical combined model yields the best prediction AUCs of 0.756, 0.812, and 0.928 in training sets, and AUCs of 0.757, 0.777 and 0.838 in testing sets, respectively. CONCLUSIONS: The combination of radiomics features and clinicopathological characteristics can effectively predict axillary pCR status in NAC breast cancer patients.

Unraveling Key m6A Modification Regulators Signatures in Postmenopausal Osteoporosis through Bioinformatics and Experimental Verification.

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis-derived BMSCs (OP-BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6-methyladenosine RNA binding protein 3) on the osteogenic traits of OP-BMSCs and identify potential therapeutic targets to boost their bone formation ability. METHODS: We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single-cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. RESULTS: Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single-cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP-BMSCs substantially impedes their proliferation and differentiation. CONCLUSION: YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP-BMSCs.

Decreased sagittal slope of the medial tibial spine and deep concavity of the lateral tibial spine are risk factors for noncontact anterior cruciate ligament injury.

PURPOSE: This study aimed to assess the relationship between the geometric features of tibial eminence and susceptibility to noncontact anterior cruciate ligament (ACL) injuries. METHODS: Patients with unilateral noncontact knee injuries between 2015 and 2021 were consecutively enroled in this study. Based on knee magnetic resonance imaging (MRI) and arthroscopic visualisation, patients were categorised into the case group (ACL rupture) and control group (ACL intact). Using MRI, the geometric features of tibial eminence were characterised by measuring the sagittal slopes, depth of concavity and coronal slopes of the inclined surfaces of the tibial spines. Univariate and multivariate logistic regressions were conducted to explore independent associations between quantified geometric indices of tibial eminence and the risk of noncontact ACL injuries. RESULTS: This study included 187 cases and 199 controls. A decreased sagittal slope of the medial tibial spine (MTSSS) (combined group: odds ratio [OR]: 0.87 [0.82, 0.92], p < 0.001; females: OR: 0.88 [0.80, 0.98], p = 0.020; males: OR: 0.87 [0.81, 0.93], p < 0.001) and an increased depth of concavity in the lateral tibial spine (LTSD) (combined group: OR: 1.51 [1.24, 1.85], p < 0.001; females: OR: 1.65 [1.12, 2.43], p = 0.012; males: OR: 1.44 [1.11, 1.89], p = 0.007) were independent risk factors for noncontact ACL injuries. Moreover, a steeper coronal slope of the inclined surface of the medial tibial spine was a significant predictor of noncontact ACL injuries for males (MTSCS: OR: 1.04 [1.01, 1.08], p = 0.015) but not for females. CONCLUSION: Geometric features of tibial eminence, particularly a decreased MTSSS and an increased LTSD, were identified as independent risk factors for noncontact ACL injuries. These findings will help clinicians identify individuals at high risk of ACL injury and facilitate the development of targeted prevention strategies. LEVEL OF EVIDENCE: Level III.

Poly (lactic-co-glycolic acid)-encapsulated Endostar-loaded calcium phosphate cement as anti-tumor bone cement for the treatment of bone metastasis in lung cancer.

Lung cancer is one of the most common malignant tumors in the world. In approximately 30%-40% of lung cancer patients, bone metastases ensues with osteolytic destruction. Worse still, intractable pain, pathological fracture, and nerve compression caused by bone metastases are currently the bottleneck of research, diagnosis, and treatment of lung cancer. Therefore, the present study aims at investigating the effectiveness of a new composite material made of calcium phosphate cement (CPC) and Endostar on repairing bone defects in vitro and in vivo. As indicated in results, the mechanical properties of CPC+Endostar and CPC+PLGA+Endostar do not differ from those of pure CPC. The PLGA-embedded Endostar slow-release microspheres were designed and prepared, and were combined with CPC. Poly (lactic-co-glycolic acid (PLGA) is a biodegradable polymer material in vivo, so the effect on its mechanical properties is negligible. CPC+Endostar and CPC+PLGA+Endostar have been proved to inhibit cell proliferation, promote apoptosis and block cell cycle in G2 phase; the expression levels of osteoclast-related genes CXCL2, TGF-ß1, IGF-1, IL-6, and RANKL were significantly decreased while osteogenic ability and alkaline phosphatase activity observably enhanced. In vivo studies have revealed that the expression levels of TRAP, RANKL, and Caspase3 in CPC+PLGA+ENDO-treated tumor tissues after 3 weeks were higher than those in other groups with the prolongation of animal treatment time, while the expression levels of OPN and BCL2 were lower than those in other groups. In hematoxylin and eosin and TUNEL staining, 3 weeks of CPC+PLGA+ENDO-treatment yielded higher tissue necrosis and apoptosis than other groups; computed tomography and magnetic resonance imaging results showed the posterior edge bone damage reduced as a result of the CPC+PLGA+ENDO grafting in vertebral pedicle. Overall, the feasibility and reliability of CPC-loaded Endostar in the treatment of bone metastasis in lung cancer were investigated in this study, so as to promote the basic research and treatment of bone metastasis in lung cancer and other malignant tumors.

m6A Methylation-Mediated Stabilization of LINC01106 Suppresses Bladder Cancer Progression by Regulating the miR-3148/DAB1 Axis.

BACKGROUND: The pivotal roles of long noncoding RNAs (lncRNAs) in the realm of cancer biology, inclusive of bladder cancer (BCa), have been substantiated through various studies. Remarkably, RNA methylation, especially m6A modification, has demonstrated its influence on both coding and noncoding RNAs. Nonetheless, the explicit impact of RNA methylation on lncRNAs and its subsequent contribution to the progression of BCa remains to be elucidated. METHODS: In the present investigation, we scrutinized the expression and m6A methylation status of LINC01106, employing quantitative real-time PCR (qRT-PCR) and methylated RNA immunoprecipitation (MeRIP)-qPCR. To decipher the regulatory mechanism underpinning LINC01106, we utilized RNA immunoprecipitation (RIP)-qPCR, methylated RNA immunoprecipitation (MeRIP) assays, and bioinformatic analysis. Furthermore, the CRISPR/dCas13b-METTL3-METTL14 system was implemented to probe the function of LINC01106. RESULTS: The findings of our study indicated that LINC01106 is under expressed and exhibits diminished m6A methylation levels in BCa tissues when compared those of normal controls. A diminished expression of LINC01106 was associated with a less favorable prognosis in BCa patients. Intriguingly, CRISPR-mediated hypermethylation of LINC01106, facilitated by dCas13b-M3-M14, abolished the malignant phenotype of the BCa cells, an effect that could be inverted by Disabled-1 (DAB1) knockdown. From a mechanistic standpoint, we identified an m6A modification site on LINC01106 and highlighted YTHDC1 as a potential reader protein implicated in this process. Additionally, a positive correlation between DAB1 and LINC01106 expression was observed, with miR-3148 potentially acting as a mediator in this relationship. CONCLUSIONS: In summary, our research unveils a suppressive regulatory role of the LINC01106/miR-3148/DAB1 axis in the progression of BCa and underscores the YTHDC1-mediated m6A modification mechanism in regards to LINC01106. These revelations propose a new therapeutic target for the management of BCa.

Associations of the serum vitamin D with mortality in postmenopausal women.

PURPOSE: Current evidence on the association of serum vitamin D with mortality in postmenopausal women is limited and inconsistent. Therefore, the purpose of this study was to examine the relationship between serum vitamin D and mortality in postmenopausal women. METHODS: In this study, we used data from the NHANES (2001-2018) and conducted a multivariate Cox regression model to examine associations between serum vitamin D and all-cause mortality, cardiovascular mortality (CVD), and cancer mortality. RESULTS: In a median follow-up period of 8.3 years, 1905 deaths of all causes were reported, 601 were due to CVD, and 385 deaths were due to cancer. After multivariable adjustment, higher serum vitamin D levels were significantly associated with a reduced risk of death. Compared to participants with lower vitamin D levels (<25 nmol/L), those with higher vitamin D levels (≥75.0 nmol/L) had a lower risk of all-cause mortality (hazard ratio 0.60, 95 % confidence interval 0.49 to 0.74), a lower risk of cardiovascular mortality (0.51, 0.35 to 0.74), and a lower risk of cancer mortality (0.43, 0.28 to 0.67). Moreover, we observed an L-shaped dose-response relationship of serum vitamin D levels with all-cause mortality, and cancer mortality, with this inflexion point being 55.9 nmol/L, and 51.2 nmol/L, respectively. CONCLUSIONS: Higher concentrations of serum vitamin D substantially correlated with a reduction in mortality risk from all-cause, CVD, and cancer in postmenopausal women. These results imply that upholding adequate vitamin D levels may help prevent premature death in postmenopausal women.

MRPL48 is a novel prognostic and predictive biomarker of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer and poses a threat to the health and survival of humans. Mitochondrial ribosomal protein L48 (MRPL48) belongs to the mitochondrial ribosomal protein family, which participates in energy production. Studies have shown that MRPL48 can predict osteosarcoma incidence and prognosis, as well as promotes colorectal cancer progression. However, the role of MRPL48 in HCC remains unknown. METHODS: TCGA, GEO, HCCDB, CPTAC, SMART, UALCAN, Kaplan-Meier plotter, cBioPortal, and MethSurv were performed for bioinformatics purposes. Quantitative RT-PCR, immunoblotting, and functional studies were conducted to validate the methodology in vitro. RESULTS: MRPL48 was greatly overexpressed in HCC tissues, compared with healthy tissue, which was subsequently demonstrated in vitro as well. The survival and regression analyses showed that MRPL48 expression is of significant clinical prognostic value in HCC. The ROC curve and nomogram analysis indicated that MRPL48 is a powerful predictor of HCC. MRPL48 methylation was adversely associated with the expression of MRPL48, and patients with a low level of methylation had poorer overall survival than those with a high level of methylation. GSEA showed that the expression of the MRPL48 was correlated with Resolution of Sister Chromatid Cohesion, Mitotic Prometaphase, Retinoblastoma Gene in Cancer, RHO Gtpases Activate Formins, Mitotic Metaphase and Anaphase, and Cell Cycle Checkpoints. An analysis of immune cell infiltration showed a significant association between MRPL48 and immune cell infiltration subsets, which impacted the survival of HCC patients. Additionally, MRPL48 knockdown reduced HCC cell proliferation, migration, and invasion in vitro. CONCLUSIONS: We demonstrated that MRPL48 expression may be associated with HCC development and prognosis. These findings may open up new research directions and opportunities for the development of HCC treatments.

Isolated traumatic gallbladder injury: A case report.

BACKGROUND: Isolated gallbladder injury (GI) (IGI) directly induced by abdominal trauma is rare. Symptoms, indications, and imaging examinations of IGI are frequently non-specific, posing tremendous diagnostic challenges, which are simple to overlook and may have severe implications. Improving doctors' understanding of gallbladder injury (GI) facilitates early detection and decreases the likelihood of severe consequences, including death. CASE SUMMARY: We report a case of IGI caused by blunt violence (after falling from three meters with the umbilicus as the stress point) and performed laparoscopic repair of the gallbladder rupture, which helps clinicians understand IGI and reduce the severe consequences of delayed diagnosis. Through extensive medical history and dynamic abdominal ultrasound evaluation, doctors can identify GI early and begin surgery, thereby decreasing the devastating repercussions of delayed diagnosis. CONCLUSION: This article aims to improve clinicians' understanding of IGI and propose a method for the diagnosis and treatment of GI.

Bone mineral density is associated with composite dietary antioxidant index among US adults: results from NHANES.

This cross-sectional study investigated the relationship between composite dietary antioxidant index (CDAI) and individual dietary antioxidant intakes, including vitamins A, C, and E, zinc, selenium, and carotenoids, and bone mineral density (BMD) in the US population aged 20 years older. We found a positive correlation between CDAI and femoral BMD. Moreover, higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. INTRODUCTION: While individual dietary antioxidants have shown beneficial effects on bone metabolism, the diverse and potentially interacting nature of dietary components may limit the accuracy of evaluating their impact on bone health. Thus, this study aims to investigate the association between CDAI and BMD. Additionally, we explore the relationship between the intake of individual components of the CDAI and BMD. METHODS: The CDAI is a novel index evaluating total dietary antioxidant intake, considering vitamins A, C, and E, zinc, selenium, and carotenoids. A cross-sectional analysis was conducted using data from participants aged ≥ 20 in the National Health and Nutrition Examination Survey (2005-2010, 2013-2014, and 2017-2018). We utilized multivariate linear regression models to examine the relationship between CDAI, individual dietary antioxidants, including vitamins A, C, and E, zinc, selenium, carotenoids, and femoral BMD. RESULTS: The final analysis included 10,584 participants with a mean age of 50.73 ± 16.65 years. After multivariate adjustment, the second to fourth quartiles of CDAI (- 2.00-0.04, 0.04-2.54, and 2.54-70.78) exhibited higher femoral BMD compared to the first quartile of CADI (- 7.34 to - 2.00). Multiple regression analysis revealed that higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. CONCLUSIONS: CDAI serves as a comprehensive tool for evaluating the overall antioxidant capacity of antioxidants in diets. Additionally, our study shows a positive correlation between CDAI and BMD, which indicates that the combined intake of dietary antioxidants may help reduce the risk of osteoporosis in adults.

A novel primary osteoporosis screening tool (POST) for adults aged 50 years and over.

PURPOSE: This study aimed to develop and validate a simple primary osteoporosis screening tool (POST) based on adults aged 50 years and older. METHODS: This study included participants aged ≥50 from the National Health and Nutrition Examination Survey. Osteoporosis was defined according to bone mineral density values. The POST was developed based on methods from previous studies. Moreover, we plotted the receiver operating characteristic curves to calculate the area under the curve (AUC) and determine the optimal cut-off value according to the weighted Youden index. In addition, we compared the performances in identifying individuals with osteoporosis between the POST and the Osteoporosis Self-assessment Tool (OST). Finally, we also assessed the performance of the POST in the Chinese population. RESULTS: Finally, a total of 6665 individuals were included in this study. The AUC values of the POST for identifying individuals with osteoporosis in the development cohort and the validation cohort were 0.81 (95% CI: 0.79-0.83) and 0.81 (95% CI: 0.77-0.84), respectively. Moreover, a POST-score ≥7 was determined as the threshold to identify individuals with osteoporosis, in which the sensitivity was greater than 90%. In addition, the POST showed significantly higher sensitivity than the OST. Finally, the POST showed an AUC of 0.75 (95% CI: 0.65-0.85) among 94 Chinese subjects aged ≥50 years old. CONCLUSIONS: POST is a convenient and effective tool for osteoporosis screening among adults aged 50 years and over, which might provide new methodological support for future osteoporosis screening.

[Research progress of Codonopsis Radix and prediction of its Q-markers].

Codonopsis Radix is a traditional tonic medicine commonly used in China, which has the effects of strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. The chemical constituents of Codonopsis species are mainly polyacetylenes, alkaloids, phenylpropanoids, lignans, terpenoids and saponins, flavonoids, steroids, organic acids, saccharides, and so on. Modern pharmacological studies showed that Codonopsis Radix also has a variety of pharmacological effects such as enhancing body immunity, protecting gastrointestinal mucosa and resisting ulcers, promoting hematopoietic function, regulating blood sugar, and delaying aging. In this paper, the chemical constituents of Codonopsis species and the pharmacological effects of Codonopsis Radix were summarized, and on this basis, the quality markers of Codonopsis Radix were analyzed. It was predicted that lobetyolin, tangshenoside I, codonopyrrolidium A, and the oligosaccharides were the possible Q-markers of Codonopsis Radix. This paper will provide scientific references for the quality evaluation and profound research and the development of Codonopsis Radix.

Study on Hydrothermal Cracking of Heavy Oil under the Coexisting Conditions of Supercritical Water and Non-condensate Gas.

This study looked at the effects of temperature, water-oil ratio, and the addition of non-condensable gas on the thermal cracking of extra-heavy oil in the lab. The goal was to learn more about the properties and reaction rates of deep extra-heavy oil under supercritical water conditions, which are not well understood. The changes in the composition of the extra-heavy oil were analyzed with and without the presence of non-condensable gas. The reaction kinetics of the thermal cracking of extra-heavy oil were quantitatively characterized and compared between the two conditions of supercritical water alone and supercritical water mixed with non-condensable gas. The results showed that (1) under supercritical water conditions, the extra-heavy oil underwent significant thermal cracking, which led to a significant increase in the amount of light components, the release of CH4, and the formation of a new component, coke, which led to a noticeable decrease in the viscosity of the oil; (2) increasing the water-oil ratio could promote the thermal cracking of extra-heavy oil and led to a significant decrease in oil viscosity, indicating a more complete thermal cracking reaction. Moreover, increasing the water-oil ratio was found to facilitate the flowability of the cracked oil; (3) the addition of non-condensable gas intensified the conversion of coke but inhibited and slowed down the thermal cracking of asphaltene, which is detrimental to the thermal cracking of extra-heavy oil; and (4) the kinetic analysis showed that the addition of non-condensable gas resulted in a decrease in the thermal cracking rate of asphaltene, which is detrimental to the thermal cracking of heavy oil.

[Study on Platelet Adhesion and Aggregation Induced by Gradient Shear Stress Using Microfluidic Chip Technology].

OBJECTIVE: To study the effect of gradient shear stress on platelet aggregation by microfluidic chip Technology. METHODS: Microfluidic chip was used to simulate 80% fixed stenotic microchannel, and the hydrodynamic behavior of the stenotic microchannel model was analyzed by the finite element analysis module of sollidwork software. Microfluidic chip was used to analyze the adhesion and aggregation behavior of platelets in patients with different diseases, and flow cytometry was used to detect expression of the platelet activation marker CD62p. Aspirin, Tirofiban and protocatechuic acid were used to treat the blood, and the adhesion and aggregation of platelets were observed by fluorescence microscope. RESULTS: The gradient fluid shear rate produced by the stenosis model of microfluidic chip could induce platelet aggregation, and the degree of platelet adhesion and aggregation increased with the increase of shear rate within a certain range of shear rate. The effect of platelet aggregation in patients with arterial thrombotic diseases were significantly higher than normal group (P<0.05), and the effect of platelet aggregation in patients with myelodysplastic disease was lower than normal group (P<0.05). CONCLUSION: The microfluidic chip analysis technology can accurately analyze and evaluate the platelet adhesion and aggregation effects of various thrombotic diseases unde the environment of the shear rate, and is helpful for auxiliary diagnosis of clinical thrombotic diseases.

Efficacy and safety of IL inhibitors, TNF-α inhibitors, and JAK inhibitors in patients with ankylosing spondylitis: a systematic review and Bayesian network meta-analysis.

Background: Biologics and Janus kinase (JAK) inhibitors are commonly used to improve ankylosing spondylitis (AS) symptoms if conventional treatments are ineffective or unsuitable. This systematic review aimed to compare the therapeutic effects and safety of JAK inhibitors, tumor necrosis factor-alpha (TNF-α) inhibitors, and interleukin (IL) inhibitors in patients with AS. Methods: We retrieved literature from various databases including Web of Science, Cochrane, Embase, PubMed, China National Knowledge Infrastructure, Weipu Journal Database, SinoMed, and WanFang Data up to February 1, 2023, and evaluated the quality of the included RCTs using the Cochrane risk-of-bias tool. R 4.1.3, STATA 15.1 were employed for network meta-analyses. Results: We identified 48 eligible articles including 8,937 patients. Ten articles were rated as "low risk", 5 as "high risk", and the others as "some concerns". In terms of efficacy, IL-17, IL-6, and JAK inhibitors were compared with TNF-α inhibitors in ASAS20 (RR =0.81, 95% CI: 0.66-0.98; RR =0.57, 95% CI: 0.35-0.95; RR =0.77, 95% CI: 0.60-0.99). IL-6 inhibitors were compared with TNF-α inhibitors in ASAS5/6 (RR =0.39, 95% CI: 0.16-0.98). IL-23, JAK inhibitors were compared with TNF-α inhibitors in BASDAI50 (RR =0.35, 95% CI: 0.20-0.60; RR =0.70, 95% CI: 0.49-0.98). IL-17 inhibitors were compared with IL-23 and IL-6 inhibitors in BASFI (MD =-1.05, 95% CI: -1.65--0.51; MD =-1.46, 95% CI: -2.02--0.97). In terms of safety, IL-6 inhibitors were compared with JAK, TNF-α inhibitors in AEs (RR =1.38, 95% CI: 1.06-1.88; RR =1.30, 95% CI: 1.01-1.70). Conclusions: TNF-α inhibitors are significantly superior to both IL and JAK inhibitors, and may be the preferable option to deal with the rapid progression of AS and severe functional limitations. IL-17 inhibitors may better improve the BASDAI50 response compared with JAK, IL-23, and TNF-α inhibitors. The efficacy and safety of IL-6 inhibitors are inferior to other types of drugs, indicating the low efficacy and high risk of IL-6 inhibitors.

Prognostic nomogram for overall survival in upper urinary tract urothelial carcinoma (UTUC) patients treated with chemotherapy: a SEER-based retrospective cohort study.

OBJECTIVE: To establish a prognostic nomogram among UTUC patients who received chemotherapy. METHODS: 1195 UTUC patients who received chemotherapy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for the period between 2004 and 2015. Patients were randomly divided into a training and a validation set. Nomogram was constructed to predict 1-, 3-, and 5-year overall survival (OS) in those patients. Receiver-operating characteristic curves (ROCs), calibration plots, and Decision curve analysis (DCA) were applied to assess and compare the discrimination, accuracy, and practicability of the nomogram with 8th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system. RESULTS: Six clinical parameters were identified as independent prognostic factors for UTUC patients' OS, including age, marital status, TNM stage, and surgical methods of the primary site. The ROC curves showed a satisfactory discrimination capacity of the nomogram, with 1-, 3-, and 5-year area under curve (AUC) values of 0.789, 0.772, and 0.763 in the training set and 0.772, 0.822, and 0.814 in the validation set, respectively. Calibration curves indicated a good agreement between actual observation and nomogram prediction. ROC and DCA curves showed our nomograms exhibited larger benefits than the 8th AJCC-TNM staging system. CONCLUSIONS: A prognostic nomogram was established and validated to present individual predictions of OS among chemotherapeutic UTUC patients. This nomogram may assist clinicians in accurate survival prognostication, treatment decision-making, and design of future clinical trials.

Efficacy and safety of percutaneous nephrolithotripsy in elderly patients: a retrospective study.

BACKGROUND: Percutaneous nephrolithotripsy (PCNL) is difficult to perform for elderly patients; thus, this study aimed to assess its efficacy and safety in elderly patients aged > 70 years, note any associations between outcomes and patient characteristics, and summarize relevant themes and observations. METHODS: Data from patients older than 70 years who had undergone PCNL for upper urinary tract calculi between January 2016 and January 2021 was retrospectively analyzed. Risk factors for postoperative complications and residual stones were analyzed using multivariate logistic regression. RESULTS: A total of 116 elderly patients underwent 122 PCNL operations, of which six underwent secondary PCNL operations, and all of which were successfully completed. The average age was 74.6 ± 4.3 years; the average stone size and operation time were 3.5 ± 1.8 (1.2-11 cm), and 71.8 ± 34.1 min, respectively. Of the participants, 16 or 13.8% had postoperative complications and 29 (25%) had residual stones after operation. The stone free rate was 75%. Multivariate analysis revealed that an American Score of Anesthesiology III was an independent risk factor for postoperative complications (odds ratio [OR] = 4.453, p = 0.031), and staghorn calculi were independent risk factors for postoperative residual calculi (OR = 31.393, p = 0.001). CONCLUSION: PCNL was shown to be safe and effective for elderly patients aged > 70 years. Further, ASA III was an independent risk factor for postoperative complications, and staghorn calculi were independent risk factors for postoperative residual calculi in elderly patients.

Transcriptomic analysis reveals genetic factors regulating early steroid-induced osteonecrosis of the femoral head.

The present study aimed to explore the signaling pathways involved in development of early steroid-induced osteonecrosis of the femoral head (SONFH) and identify diagnostic biomarkers regulating peripheral blood in SONFH patients. We downloaded transcriptome data and identified differentially expressed genes (DEGs) using the R software. We used ClusterProfiler to perform enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, and analyzed protein-protein interactions using the STRING database. Network X was used to visualize the networks in Python. A total of 584 DEGs were identified, of which 294 and 290 were upregulated and downregulated, respectively. Enrichment analysis showed that the DEGs were mainly involved in red blood cell differentiation, cell protein catabolism, gas transportation, activation of myeloid leukocytes, phagocytosis, and inflammatory response. Pathway analysis revealed that these DEGs were involved in regulation of mitophagy-animal, human T-cell leukemia virus-1 infection, Forkhead box O, phagocytosis, osteoclast differentiation, and cytokine-cytokine receptor interaction. Quantitative real-time polymerase chain reaction results were consistent with findings from protein-protein interaction network analysis. Several genes, including peroxiredoxin 2, haptoglobin, matrix metallopeptidase 8, formyl peptide receptor 2, and integrin subunit alpha X, promote SONFH occurrence by regulating the redox, inflammatory response, and osteoblast and osteoclast structure and function pathways. They may be important targets for designing approaches for early diagnosis and treatment of SONFH.

Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis.

Nocardia rubra cell-wall skeleton (Nr-CWS) is reported as an external immunotherapeutic enhancer with the advantage of antitumor effect on human cancers. However, the immune regulatory role of Nr-CWS is not fully illustrated. We studied mouse CD4+ T lymphocytes isolated from mice spleen were induced by Nr-CWS and observed that the differentiation of Th1 CD4+ T cells and the cytokines of IL-2, TNF-α, IFN-γ were all enhanced by Nr-CWS. Furthermore, RNA sequencing was conducted to investigate the different mRNA profiling induced by Nr-CWS. We observed that paired box 8 (PAX8) was significantly up-regulated in Nr-CWS-treated Th1 cells compared to control. As a transcription factor, chromatin immunoprecipitation sequencing was carried out to study the genome-wide distribution of PAX8. Interestingly, we found that the binding domain of PAX8 was elevated by Nr-CWS, and the target genes associated with these binding sites showed a positive correlation between their transcription and PAX8 binding strength. Finally, we determined that Nr-CWS could enhance the activity of the PI3 K/Akt signaling pathway. Akt agonist could mimic the effect of Nr-CWS for PAX8 up-regulation, while Akt inhibitor compromised the expression of PAX8. Taken together, we determined a novel role of Nr-CWS in boosting the activity of Th1 maturation via the PI3 K/Akt/PAX8 axis.

Facile Synthesis of Multifunctional Magnetoplasmonic Au-MnO Hybrid Nanocomposites for Cancer Theranostics.

Significant attention is paid to the design of magnetoplasmonic nanohybrids, which exploit synergistic properties for biomedical applications. Here, a facile method was employed to prepare plasmonic magnetic Au-MnO heterostructured hybrid nanoparticles for imaging-guided photothermal therapy of cancers in vitro, with the view to reducing the serious drawbacks of chemotherapy and gadolinium-based contrast agents. The biocompatibility of the prepared Au-MnO nanocomposites was further enhanced by Food and Drug Administration (FDA)-approved triblock copolymers Pluronic® F-127 and chitosan oligosaccharide (COS), with complementary support to enhance the absorption in the near-infrared (NIR) region. In addition, synthesized COS-PF127@Au-MnO nanocomposites exhibited promising contrast enhancement in T1 MR imaging with a good r1 relaxivity value (1.2 mM-1 s-1), demonstrating a capable substitute to Gd-based toxic contrast agents. In addition, prepared COS-PF127@Au-MnO hybrid nanoparticles (HNPs) produced sufficient heat (62 °C at 200 µg/mL) to ablate cancerous cells upon 808 nm laser irradiation, inducing cell toxicity, and apoptosis. The promising diagnostic and photothermal therapeutic performance demonstrated the appropriateness of the COS-PF127@Au-MnO HNPs as a potential theranostic agent.