Prognostic model incorporating immune checkpoint genes to predict the immunotherapy efficacy for lung adenocarcinoma: a cohort study integrating machine learning algorithms.

This study aimed to develop and validate a nomogram based on immune checkpoint genes (ICGs) for predicting prognosis and immune checkpoint blockade (ICB) efficacy in lung adenocarcinoma (LUAD) patients. A total of 385 LUAD patients from the TCGA database and 269 LUAD patients in the combined dataset (GSE41272 + GSE50081) were divided into training and validation cohorts, respectively. Three different machine learning algorithms including random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression analysis, and support vector machine (SVM) were employed to select the predictive markers from 82 ICGs to construct the prognostic nomogram. The X-tile software was used to stratify patients into high- and low-risk subgroups based on the nomogram-derived risk scores. Differences in functional enrichment and immune infiltration between the two subgroups were assessed using gene set variation analysis (GSVA) and various algorithms. Additionally, three lung cancer cohorts receiving ICB therapy were utilized to evaluate the ability of the model to predict ICB efficacy in the real world. Five ICGs were identified as predictive markers across all three machine learning algorithms, leading to the construction of a nomogram with strong potential for prognosis prediction in both the training and validation cohorts (all AUC values close to 0.800). The patients were divided into high- (risk score ≥ 185.0) and low-risk subgroups (risk score < 185.0). Compared to the high-risk subgroup, the low-risk subgroup exhibited enrichment in immune activation pathways and increased infiltration of activated immune cells, such as CD8 + T cells and M1 macrophages (P < 0.05). Furthermore, the low-risk subgroup had a greater likelihood of benefiting from ICB therapy and longer progression-free survival (PFS) than did the high-risk subgroup (P < 0.05) in the two cohorts receiving ICB therapy. A nomogram based on ICGs was constructed and validated to aid in predicting prognosis and ICB treatment efficacy in LUAD patients.

Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography.

BACKGROUND: Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage. METHODS: This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage. RESULTS: The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15 mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV. CONCLUSIONS: Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.

Predictive Model to Identify the Long Time Survivor in Patients with Glioblastoma: A Cohort Study Integrating Machine Learning Algorithms.

We aimed to develop and validate a predictive model for identifying long-term survivors (LTS) among glioblastoma (GB) patients, defined as those with an overall survival (OS) of more than 3 years. A total of 293 GB patients from CGGA and 169 from TCGA database were assigned to training and validation cohort, respectively. The differences in expression of immune checkpoint genes (ICGs) and immune infiltration landscape were compared between LTS and short time survivor (STS) (OS<1.5 years). The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify the genes differentially expressed between LTS and STS. Three different machine learning algorithms were employed to select the predictive genes from the overlapping region of DEGs and WGCNA to construct the nomogram. The comparison between LTS and STS revealed that STS exhibited an immune-resistant status, with higher expression of ICGs (P<0.05) and greater infiltration of immune suppression cells compared to LTS (P<0.05). Four genes, namely, OSMR, FMOD, CXCL14, and TIMP1, were identified and incorporated into the nomogram, which possessed good potential in predicting LTS probability among GB patients both in the training (C-index, 0.791; 0.772-0.817) and validation cohort (C-index, 0.770; 0.751-0.806). STS was found to be more likely to exhibit an immune-cold phenotype. The identified predictive genes were used to construct the nomogram with potential to identify LTS among GB patients.

SEU2-Net: multi-scale U2-Net with SE attention mechanism for liver occupying lesion CT image segmentation.

Liver occupying lesions can profoundly impact an individual's health and well-being. To assist physicians in the diagnosis and treatment of abnormal areas in the liver, we propose a novel network named SEU2-Net by introducing the channel attention mechanism into U2-Net for accurate and automatic liver occupying lesion segmentation. We design the Residual U-block with Squeeze-and-Excitation (SE-RSU), which is to add the Squeeze-and-Excitation (SE) attention mechanism at the residual connections of the Residual U-blocks (RSU, the component unit of U2-Net). SEU2-Net not only retains the advantages of U2-Net in capturing contextual information at multiple scales, but can also adaptively recalibrate channel feature responses to emphasize useful feature information according to the channel attention mechanism. In addition, we present a new abdominal CT dataset for liver occupying lesion segmentation from Peking University First Hospital's clinical data (PUFH dataset). We evaluate the proposed method and compare it with eight deep learning networks on the PUFH and the Liver Tumor Segmentation Challenge (LiTS) datasets. The experimental results show that SEU2-Net has state-of-the-art performance and good robustness in liver occupying lesions segmentation.

Construction of a Functional Nucleic Acid-Based Artificial Vesicle-Encapsulated Composite Nanoparticle and Its Application in Retinoblastoma-Targeted Theranostics.

Retinoblastoma (RB) is an aggressive tumor of the infant retina. However, the ineffective targeting of its theranostic agents results in poor imaging and therapeutic efficacy, which makes it difficult to identify and treat RB at an early stage. In order to improve the imaging and therapeutic efficacy, we constructed an RB-targeted artificial vesicle composite nanoparticle. In this study, the MnO2 nanosponge (hMNs) was used as the core to absorb two fluorophore-modified DNAzymes to form the Dual/hMNs nanoparticle; after loaded with the artificial vesicle derived from human red blood cells, the RB-targeted DNA aptamers were modified on the surface, thus forming the Apt-EG@Dual/hMNs complex nanoparticle. The DNA aptamer endows this nanoparticle to target the nucleolin-overexpressed RB cell membrane specifically and enters cells via endocytosis. The nanoparticle could release fluorophore-modified DNAzymes and supplies Mn2+ as a DNAzyme cofactor and a magnetic resonance imaging (MRI) agent. Subsequently, the DNAzymes can target two different mRNAs, thereby realizing fluorescence/MR bimodal imaging and dual-gene therapy. This study is expected to provide a reliable and valuable basis for ocular tumor theranostics.

Prospects for daily online adaptive radiotherapy for cervical cancer: Auto-contouring evaluation and dosimetric outcomes.

BACKGROUND: Training senior radiation therapists as "adapters" to manage influencers and target editing is critical in daily online adaptive radiotherapy (oART) for cervical cancer. The purpose of this study was to evaluate the accuracy and dosimetric outcomes of automatic contouring and identify the key areas for modification. METHODS: A total of 125 oART fractions from five postoperative cervical cancer patients and 140 oART fractions from five uterine cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective study. The same adaptive treatments were replanned using the Ethos automatic contours workflow without manual contouring edits. The clinical target volume (CTV) was subdivided into several separate regions, and the average surface distance dice (ASD), centroid deviation, dice similarity coefficient (DSC), and 95% Hausdorff distance (95% HD) were used to evaluate contouring for the above portions. Dosimetric results from automatic oART plans were compared to supervised oART plans to evaluate target volumes and organs at risk (OARs) dose changes. RESULTS: Overall, the paired CTV had high overlap rates, with an average DSC value greater than 0.75. The uterus had the largest consistency differences, with ASD, centroid deviation, and 95% HD being 2.67 ± 1.79 mm, 17.17 ± 12 mm, and 10.45 ± 5.68 mm, respectively. The consistency differences of the lower nodal CTVleft and nodal CTVright were relatively large, with ASD, centroid deviation, and 95% HD being 0.59 ± 0.53 mm, 3.6 ± 2.67 mm, and 5.41 ± 4.08 mm, and 0.59 ± 0.51 mm, 3.6 ± 2.54 mm, and 4.7 ± 1.57 mm, respectively. The automatic online-adapted plan met the clinical requirements of dosimetric coverage for the target volume and improved the OAR dosimetry. CONCLUSIONS: The accuracy of automatic contouring from the Ethos adaptive platform is considered clinically acceptable for cervical cancer, and the uterus, upper vaginal cuff, and lower nodal CTV are the areas that need to be focused on in training.

LdCyPA attenuates MAPK pathway to assist Leishmania donovani immune escape in host cells.

BACKGROUND: Visceral leishmaniasis is a neglected tropical disease affecting millions of people worldwide. Macrophages serve as the primary host cells for L. donovani, the immune response capability of these host cells is crucial for parasites' intracellular survival. L. donovani peptidyl-prolyl cis/trans isomerase Cyclophilin A (LdCypA) is a key protein for L. donovani intracellular proliferation, while the molecular mechanism conducive to intracellular survival of parasites remains elusive. METHODS: In this study, we generated a macrophage cell line overexpressing LdCyPA to investigate its role in controlling host immunity and promoting intracellular immune escape of L. donovani. RESULTS: It was discovered that the overexpression of the LdCyPA cell line regulated the host immune response following infection by downregulating the proportion of M1-type macrophages, promoting the secretion of the anti-inflammatory factor IL-4, and inhibiting the secretion of pro-inflammatory factors like IL-12, IFN-γ, TNF-α, and INOS. Transcriptome sequencing and mechanistic validation, meanwhile, demonstrated that cells overexpressing LdCyPA controlled the immune responses that followed infection by blocking the phosphorylation of P38 and JNK1/2 proteins in the MAPK signaling pathway and simultaneously increasing the phosphorylation of ERK proteins, which helped the L. donovani escape immune recognition. CONCLUSION: Our findings thus pave the way for the development of host-directed antiparasitic drugs by illuminating the pro-Leishmania survival mechanism of L. donovani cyclophilin A and exposing a novel immune escape strategy for L. donovani that targets host cellular immune regulation.

[Effects of Cytokines on Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia].

OBJECTIVE: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits. RESULTS: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated. CONCLUSION: Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

3WJ RNA Nanoparticles-Aptamer Functionalized Exosomes From M2 Macrophages Target BMSCs to Promote the Healing of Bone Fractures.

Up to now, impaired bone regeneration severely affects the healing of bone fractures, thus bringing tremendous suffering to patients. As a vital mediator between inflammatory response and bone regeneration, M2 macrophage-derived exosomes (M2-Exos) attenuate inflammation and promote tissue repair. However, due to a lack of specific targeting property, M2-Exos will be rapidly eliminated after systematic administration, thus compromising their effectiveness in promoting bone regeneration. To solve this hurdle, we initially harvested and characterized the pro-osteogenic properties of M2-Exos. A bone marrow mesenchymal stem cell (BMSC)-specific aptamer was synthesized and 3-way junction (3WJ) RNA nanoparticles were applied to conjugate the BMSC-specific aptamer and M2-Exos. In vitro assays revealed that M2-Exos bore the representative features of exosomes and significantly promoted the proliferation, migration, and osteogenic differentiation of BMSCs. 3WJ RNA nanoparticles-aptamer functionalized M2-Exos (3WJ-BMSCapt/M2-Exos) maintained the original physical characteristics of M2-Exos, but bore a high specific binding ability to BMSCs. Furthermore, when being systemically administered in the mice model with femoral bone fractures, these functionalized M2-Exos mainly accumulated at the bone fracture site with a slow release of exosomal cargo, thereby significantly accelerating the healing processes compared with the M2-Exos group. Our study indicated that the 3WJ-BMSCapt/M2-Exos with BMSCs targeting ability and controlled release would be a promising strategy to treat bone fractures.

Recent theranostic applications of hydrogen peroxide-responsive nanomaterials for multiple diseases.

It is well established that hydrogen peroxide (H2O2) is associated with the initiation and progression of many diseases. With the rapid development of nanotechnology, the diagnosis and treatment of those diseases could be realized through a variety of H2O2-responsive nanomaterials. In order to broaden the application prospects of H2O2-responsive nanomaterials and promote their development, understanding and summarizing the design and application fields of such materials has attracted much attention. This review provides a comprehensive summary of the types of H2O2-responsive nanomaterials including organic, inorganic and organic-inorganic hybrids in recent years, and focused on their specific design and applications. Based on the type of disease, such as tumors, bacteria, dental diseases, inflammation, cardiovascular diseases, bone injury and so on, key examples for above disease imaging diagnosis and therapy strategies are introduced. In addition, current challenges and the outlook of H2O2-responsive nanomaterials are also discussed. This review aims to stimulate the potential of H2O2-responsive nanomaterials and provide new application ideas for various functional nanomaterials related to H2O2.

[Expression and Prognostic Value of Cytokines in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the expression and prognostic value of cytokines in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: Clinical data of 62 patients diagnosed with DLBCL in the First People's Hospital of Yunnan Province from June 2017 to November 2018 were collected. The differences in expression levels of 14 serum cytokines [interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, TNF-ß] in patients with different survival outcomes, and the impact of the cytokines on 3-year progression-free survival (PFS) and 3-year overall survival (OS) of patients with DLBCL were analyzed retrospectively. RESULTS: Among the 14 cytokines, only the expression of IL-10 was significantly different in patients with different survival outcomes (P =0.007). According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for IL-10 was 11.74 pg/ml. Serum IL-10 was positively correlated with infection markers procalcitonin (PCT) (r =0.321, P =0.029), C-reactive protein (CRP) (r =0.320, P =0.013) and tumor burden index lactate dehydrogenase (LDH) (r =0.439, P <0.001) in newly diagnosed DLBCL patients. The level of IL-10 in patients with pulmonary infection was significantly higher than that in patients without pulmonary infection (P =0.012). However, there was no statistically significant difference on the 3-year survival outcomes between patients with or without pulmonary infection. There was no significant difference in IL-10 level in patients with different Ann Arbor stages (P >0.05). Patients with high IL-10 level (IL-10>11.74 pg/ml) had significantly higher LDH level than those with low IL-10 level (IL-10≤11.74 pg/ml) (P <0.001). The 3-year PFS rate and 3-year OS rate of DLBCL patients with high IL-10 level were significantly lower than those of low IL-10 level group [(44.4±11.7)% vs (81.8±5.8)%, P <0.001; (61.6±11.5)% vs (93.2±3.8)%, P =0.001]. CONCLUSION: Serum IL-10 level in newly diagnosed DLBCL patients can reflect the inflammatory state of the body, which may be related to tumor load. Newly diagnosed DLBCL patients with serum IL-10>11.74 pg/ml have higher early mortality and worse prognosis.

Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1.

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.

Posterior unilateral small fenestration of lamina combined with a custom-made Y-shaped fracture reduction device for the treatment of severe thoracolumbar burst fracture: a prospective comparative study.

BACKGROUND: The purpose was to evaluate the clinical effect of a custom-made Y-shaped fracture fragment reduction device and to assist in posterior unilateral small fenestration of lamina to reduce the fracture fragments. METHODS: In this study, 40 patients were assigned to one of two groups: the traditional reduction device group (TRG) or the Y-shaped reduction device group (YRG). All patients underwent posterior unilateral small fenestration of the lamina and direct decompression through the spinal canal. And the operation time (OT), intraoperative bleeding (IB), preoperative, postoperative, and final follow-up data on the spinal stenosis rate (SSR), Cobb angle, the anterior compression ratio of injured vertebrae (ACRIV), and ASIA neurological function grade were compared between the two groups. RESULT: There were no complications, including vascular and nerve injury, serious postoperative infection, internal fixation fracture, or loosening, for any of the patients. And the average follow-up time of the two groups was 14.2 months, the average operation time of the TRG was 236.6 min, and the average intraoperative blood loss was 357.20 ml. Moreover, the average operation time of the YRG was 190.6 min, and the average intraoperative blood loss was 241.5 ml. There were significant differences between the two groups in terms of operation duration and intraoperative blood loss. The YRG's was lower than that of the TRG. Besides, there was no difference in SSR, Cobb angle, ACRIV, or neurological recovery between the two groups before or immediately after the operation or at the last follow-up. CONCLUSION: The Y-shaped fracture reduction device can reduce the fracture fragments and the OT and IB stably; it also has satisfactory postoperative curative effects and clinical utility.

Personalized Brachytherapy for a Herlyn-Werner-Wunderlich Syndrome Patient with Endometrial Cancer: A Case Report.

Purpose: Endometrial carcinoma (EC) is a common gynecological malignancy. Vaginal cuff brachytherapy (VBT) is an adjuvant treatment for EC. Since a single-channel cylinder sometimes delivers inadequate dose coverage to the vaginal apex, three-dimensional (3D) printing technology can be used to achieve satisfactory dose distribution. Here, we report the first case of an EC patient with Herlyn-Werner-Wunderlich syndrome (HWWS) treated with VBT using 3D-printed applicators. Case Presentation: Here, we present a case study of an endometrial cancer patient with HWWS who underwent surgery. During adjuvant radiotherapy, 3D-printed applicators were used in VBT. To accomplish the reconstruction of the source pathways on magnetic resonance imaging, catheters with copper sulfate were placed in two 3D-printed applicators. The early tolerance of this treatment was positive. During the 6-month follow-up, locoregional recurrence was not detected. Conclusion: Our findings strongly indicate that VBT with 3D-printed applicators may be a reasonable treatment option for EC with HWWS.

Spontaneous rupture of an unscarred uterus during pregnancy: A rare but life-threatening emergency: Case series.

RATIONALE: In most cases, uterine rupture occurs during the third trimester of pregnancy or during labor. Even fewer reports have been published about the occurrence of this condition without a gynecologic history of any surgical procedure. Due to their scarcity and variable clinical presentation, early diagnosis of uterine rupture may be difficult, and if the diagnosis is not timely, the condition may be life-threatening. PATIENT CONCERNS: Herein, 3 cases of uterine rupture from a single institution are described. Three patients are at different gestational weeks and all have no history of uterine surgery. They came to the hospital due to acute abdominal pain, which is characterized by severe and persistent pain in the abdomen, with no apparent vaginal bleeding. DIAGNOSES: All 3 patients were diagnosed with uterine rupture during the operation. INTERVENTIONS: One patient underwent uterine repair surgery; while the other 2 underwent subtotal hysterectomy due to persistent bleeding and pathological examination after surgery confirmed placenta implantation. OUTCOMES: The patients recovered well after the operation, and no discomfort occurred in the follow-up. LESSONS: Acute abdominal pain during pregnancy can pose both diagnostic and therapeutic challenges. It is important to consider the possibility of uterine rupture, even in cases where there is no history of prior uterine surgery. The key to the treatment of uterine rupture is to shorten the diagnosis time as much as possible, this potential complication should be carefully monitored for and promptly addressed to ensure the best possible outcomes for both the mother and the developing fetus.

Optimal cisplatin cycles in locally advanced cervical carcinoma patients treated with concurrent chemoradiotherapy.

PURPOSE: To analyze the effect of cisplatin cycles on the clinical outcomes of patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT). METHODS: This study included 749 patients with LACC treated with CCRT between January 2011 and December 2015. A receiver operating characteristic (ROC) curve was used to analyze the optimal cut-off of cisplatin cycles in predicting clinical outcomes. Clinicopathological features of the patients were compared using the Chi-square test. Prognosis was assessed using log-rank tests and Cox proportional hazard models. Toxicities were compared among different cisplatin cycle groups. RESULTS: Based on the ROC curve, the optimal cut-off of the cisplatin cycles was 4.5 (sensitivity, 64.3%; specificity, 54.3%). The 3-year overall, disease-free, loco-regional relapse-free, and distant metastasis-free survival for patients with low-cycles (cisplatin cycles < 5) and high-cycles (≥ 5) were 81.5% and 89.0% (P < 0.001), 73.4% and 80.1% (P = 0.024), 83.0% and 90.8% (P = 0.005), and 84.9% and 86.8% (P = 0.271), respectively. In multivariate analysis, cisplatin cycles were an independent prognostic factor for overall survival. In the subgroup analysis of high-cycle patients, patients who received over five cisplatin cycles had similar overall, disease-free, loco-regional relapse-free, and distant metastasis-free survival to patients treated with five cycles. Acute and late toxicities were not different between the two groups. CONCLUSION: Cisplatin cycles were associated with overall, disease-free, and loco-regional relapse-free survival in LACC patients who received CCRT. Five cycles appeared to be the optimal number of cisplatin cycles during CCRT.

Modification and application of "zero-line" incision design in total endoscopic gasless unilateral axillary approach thyroidectomy: A preliminary report.

Introduction: Gasless unilateral trans-axillary approach (GUA) thyroidectomy has witnessed rapid development in technologies and applications. However, the existence of surgical retractors and limited space would increase the difficulty of guaranteeing the visual field and disturb safe surgical manipulation. We aimed to develop a novel zero-line method for incision design to access optimal surgical manipulation and outcomes. Methods: A total of 217 patients with thyroid cancer who underwent GUA were enrolled in the study. Patients were randomly classified into two groups (classical incision and zero-line incision), and their operative data were collected and reviewed. Results: 216 enrolled patients underwent and completed GUA; among them, 111 patients were classified into the classical group, and 105 patients were classified into the zero-line group, respectively. Demographic data, including age, gender, and the primary tumor side, were similar between the two groups. The duration of surgery in the classical group was longer (2.66 ± 0.68 h) than in the zero-line group (1.40 ± 0.47 h) (p < 0.001). The counts of central compartment lymph node dissection were higher in the zero-line group (5.03 ± 3.02 nodes) than that in the classical group (3.05 ± 2.68 nodes) (p < 0.001). The score of postoperative neck pain was lower in the zero-line group (1.0 ± 0.36) than that in the classical group (3.3 ± 0.54) (p < 0.05). The difference in cosmetic achievement was not statistically significant (p > 0.05). Conclusion: The "zero-line" method for GUA surgery incision design was simple but effective for GUA surgery manipulation and worth promoting.

A Maximization of the Proton Conductivity of Sulfonated Poly(Ether Ether Ketone) with Grafted Segments Containing Multiple, Flexible Propanesulfonic Acid Groups.

To enhance the proton conductivity of sulfonated poly(ether ether ketone) (SPEEK), proton-conducting groups are required to be covalently connected to SPEEK and form proton-conducting channels. Herein, SPEEK fully grafted with segments containing multiple, flexible propanesulfonic acid groups (MS-SPEEK-102) is successfully prepared. Compared with SPEEK, MS-SPEEK-102 exhibits a higher proton conductivity of 8.3 × 10-2  S cm-1 at 80 °C with 98% relative humidity, and consequently a greater power density of 0.530 W cm-2 at 60 °C. These can be ascribed to the increased number of sulfonic acid groups, and ample, uninterrupted proton-conducting channels constructed by the movement of the maximum content, flexible side-chain segments. This approach offers an idea for obtaining a proton exchange membrane with good proton conductivity based on SPEEK.