Purpose: Metastatic rectal cancer (mRC) is a highly lethal and complex disease that demands a multidisciplinary treatment approach. However, the clinical effectiveness of radiotherapy (RT) for de novo mRC remains controversial and uncertain. Methods: This retrospective cohort study examined medical records from Kaohsiung Chang Gung Memorial Hospital for patients with histologically confirmed de novo mRC diagnosed between January 2015 and December 2020. All patients received standard systemic therapy and radical surgery when feasible. The primary outcome, overall survival (OS), was assessed using the Kaplan-Meier method. Multivariable analysis was performed using a Cox regression model. Results: Among 271 patients included in the analysis, 117 received RT and 154 did not. The median OS was significantly longer in the RT group compared with the non-RT group (27.8 months vs. 21.9 months; P=0.046). Multivariate analysis identified several independent predictors of OS: age ≥65 years (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.26–2.27; P=0.001), primary tumor resection (HR, 2.62; 95% CI, 1.90–3.61; P<0.001), M1b or M1c disease (HR, 1.97; 95% CI, 1.44–2.69; P<0.001), and receipt of RT (HR, 1.41; 95% CI, 1.02–1.94; P=0.036). Conclusion RT significantly improves OS in patients with mRC, underscoring its role in treatment strategies. These findings support its inclusion in therapeutic protocols and highlight the need for larger, multicenter trials to confirm and extend these results.

Background: Cerebral hypoxia-ischemia impairs brain development in extremely preterm infants and is associated with poor neurological outcomes. Near-infrared spectroscopy (NIRS) is a noninvasive continuous monitoring method for regional cerebral oxygen saturation (rcSO2).Purpose: This study evaluated the clinical feasibility and neurological impact of a neurocritical care bundle that incorporates prolonged multidisciplinary hemodynamic monitoring and a stepwise management algorithm. Methods: Preterm infants with a gestational age (GA) ≤28 weeks or birth weight (BW) ≤1,000 g were prospectively enrolled in a bundle group subjected to NIRS for rcSO2, electrical cardiometry for cardiac output, and daily brain and cardiac echography during the first 72 hours of life. Monitoring was repeated weekly in the first month and then monthly until discharge or the term-equivalent age (TEA) was reached. We implemented a stepwise management algorithm for treating cerebral hypoxia. The primary outcome was a composite of mortality and adverse neurological events (structural abnormalities or electroencephalogram-confirmed seizures) before discharge. The secondary outcomes were the physiological pattern of rcSO2 within the initial 72 hours and up to discharge or TEA. Results: Thirty preterm infants (GA, 27.1±2.0 weeks; BW, 830±225 g) were enrolled in the bundle group. The mean time-averaged rcSO2 (66.8%±10.3%) was not associated with GA or BW. However, postnatal age appeared to influence physiological rcSO2 changes, given that rcSO2 values were higher during the initial 72 hours than at subsequent intervals. Seven infants (23.3%) had poor outcomes and significantly lower time-averaged rcSO2 (51.1% [50.0%–65.2%] vs. 71.8% [67.1%–73.1%], P=0.002). Multivariate regression indicated that a lower rcSO2 was an independent risk factor, and a 65% threshold showed an optimal predictive value for poor outcomes. Conclusion The neurocritical care bundle helped identify preterm infants at risk of cerebral hypoxia, and lower rcSO2 was an independent risk factor for composite mortality and adverse neurological outcomes.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:Based on bioinformatics analysis, this study aimed to identify the complement component 5a receptor 1(C5aR1)and chemokine C-C motif ligand-2(CCL2)genes in vascular dementia(VaD)and to explore the expression and clinical significance of serum C5aR1 and CCL2 levels in VaD patients.Methods:The GSE122063 dataset was selected from the Gene Expression Omnibus(GEO)database to screen for consistently differentially expressed genes in the frontal and temporal lobes of VaD patients and non-dementia patients.The Matascape database was used to analyze the functions and pathways of differentially expressed genes, and the STRING network and Cytoscape software were used to identify key genes.In this case-control study, 53 VaD patients seeking care at the Department of Neurology of the Affiliated Hospital of Jiangsu University between January 2022 and December 2022 were included in the VaD group, and 50 non-dementia individuals were included in the control group.General information, Montreal Cognitive Assessment(MoCA)scores, Mini-Mental State Examination(MMSE)scores, and scores of the total cerebral small vessel disease(CSVD)burden were collected for both groups, and serum C5aR1 and CCL2 expression was detected.The correlation of serum C5aR1 and CCL2 levels with MoCA scores, MMSE scores, and scores of the total CSVD burden in the VaD group was analyzed.Receiver operating characteristic(ROC)curve analysis was used to assess the diagnostic value of serum C5aR1 and CCL2 levels in VaD.Results:In the GSE122063 dataset, compared with non-dementia patients, there were 43 upregulated genes and 63 downregulated genes simultaneously in the frontal and temporal lobes in the VaD group.After importing 106 genes into the Cytoscape software and using the Stress and Betweenness algorithms in the cytoHubba plugin, two key genes, C5aR1 and CCL2, were identified.Serum levels of C5aR1[(57.25±10.34)μg/L vs.(43.26±8.24)μg/L, t=7.607, P<0.001]and CCL2[(210.42±42.19)ng/L vs.(151.73±36.04)ng/L, t=7.570, P<0.001]in the VaD group were higher than those in the control group.Serum levels of C5aR1 and CCL2 were negatively correlated with MoCA scores( r=-0.691, -0.668, P<0.001)and MMSE scores( r=-0.736, -0.729, P<0.001), and positively correlated with scores of the total CSVD burden( r=0.598, 0.582, P<0.001).The areas under the ROC curve for serum C5aR1 and CCL2 levels in diagnosing VaD was 0.838 and 0.845, respectively.The area under the ROC curve with the combination of C5aR1 and CCL2 for the diagnosis of VaD was 0.896. Conclusions:Serum levels of C5aR1 and CCL2 are elevated in VaD patients and closely related to their cognitive function and the total CSVD burden, and may be used as an auxiliary diagnostic tool for VaD patients.

Objective:To establish venetoclax-resistant acute myeloid leukemia(AML)cell lines,assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family,and investigate their resistance mechanisms.Methods:CCK-8 method was used to screen AML cell lines(MV4-11,MOLM13,OCI-AML2)that were relatively sensitive to venetoclax.Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines.Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry.BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients.Results:Venetoclax-resistant cell lines of MV4-11,MOLM13,and OCI-AML2 were successfully established,with IC50 values exceeding 10-fold.Under the same concentration of venetoclax,the apoptosis rate of resistant cells decreased significantly(P＜0.05).BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins(such as BIM,BID and NOXA).RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines.Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results.Conclusion:The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax.The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM,BID,and NOXA,which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Objective:Based on bioinformatics analysis, this study aimed to identify the complement component 5a receptor 1(C5aR1)and chemokine C-C motif ligand-2(CCL2)genes in vascular dementia(VaD)and to explore the expression and clinical significance of serum C5aR1 and CCL2 levels in VaD patients.Methods:The GSE122063 dataset was selected from the Gene Expression Omnibus(GEO)database to screen for consistently differentially expressed genes in the frontal and temporal lobes of VaD patients and non-dementia patients.The Matascape database was used to analyze the functions and pathways of differentially expressed genes, and the STRING network and Cytoscape software were used to identify key genes.In this case-control study, 53 VaD patients seeking care at the Department of Neurology of the Affiliated Hospital of Jiangsu University between January 2022 and December 2022 were included in the VaD group, and 50 non-dementia individuals were included in the control group.General information, Montreal Cognitive Assessment(MoCA)scores, Mini-Mental State Examination(MMSE)scores, and scores of the total cerebral small vessel disease(CSVD)burden were collected for both groups, and serum C5aR1 and CCL2 expression was detected.The correlation of serum C5aR1 and CCL2 levels with MoCA scores, MMSE scores, and scores of the total CSVD burden in the VaD group was analyzed.Receiver operating characteristic(ROC)curve analysis was used to assess the diagnostic value of serum C5aR1 and CCL2 levels in VaD.Results:In the GSE122063 dataset, compared with non-dementia patients, there were 43 upregulated genes and 63 downregulated genes simultaneously in the frontal and temporal lobes in the VaD group.After importing 106 genes into the Cytoscape software and using the Stress and Betweenness algorithms in the cytoHubba plugin, two key genes, C5aR1 and CCL2, were identified.Serum levels of C5aR1[(57.25±10.34)μg/L vs.(43.26±8.24)μg/L, t=7.607, P<0.001]and CCL2[(210.42±42.19)ng/L vs.(151.73±36.04)ng/L, t=7.570, P<0.001]in the VaD group were higher than those in the control group.Serum levels of C5aR1 and CCL2 were negatively correlated with MoCA scores( r=-0.691, -0.668, P<0.001)and MMSE scores( r=-0.736, -0.729, P<0.001), and positively correlated with scores of the total CSVD burden( r=0.598, 0.582, P<0.001).The areas under the ROC curve for serum C5aR1 and CCL2 levels in diagnosing VaD was 0.838 and 0.845, respectively.The area under the ROC curve with the combination of C5aR1 and CCL2 for the diagnosis of VaD was 0.896. Conclusions:Serum levels of C5aR1 and CCL2 are elevated in VaD patients and closely related to their cognitive function and the total CSVD burden, and may be used as an auxiliary diagnostic tool for VaD patients.

Objective:To investigate the application and clinical efficacy of customized, 3D-printed femoral bone marrow stems in the revision of tumor prostheses.Methods:A retrospective analysis was performed for the data of 11 patients (7 males and 4 females) aged 53.1±11.7 years (range, 38-75 years), who underwent 3D-printed customized revision of femoral intramedullary stems due to loosening of femoral tumor prostheses at the 960th Hospital of the Joint Support Force of the PLA from June 2021 to June 2023. The pathological types of tumors associated with the initial surgeries included 4 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 1 case of chondrosarcoma, and 1 case of plasma cell tumor. The tumor was located at the distal femur in 8 cases and the proximal femur in 3 cases. The procedures included 3 initial revisions, 7 secondary revisions, and 1 tertiary revision. The average limb shortening measured 4.6±2.2 cm (range, 2.5-9.0 cm). Prior to revision, all prostheses were fixed with bone cement, revealing enlargement of the femoral medullary cavity and cortical bone thinning. Among them, 5 cases had intramedullary stems permeabilizing the femoral cortex, and 1 case had femoral cleavage fractures. All 11 patients received personalized data for the design and 3D printing of femoral bone marrow stems.Results:The lengths and diameters of the 3D-printed porous femoral bone marrow stems ranged from 80 to 160 mm and 20 to 22 mm, respectively. Ten patients were fitted with cylindrical intramedullary handles, while one received a conical intramedullary handle. A successful revision with the 3D-printed stems was achieved in 10 patients; however, 1 case failed to accommodate the conical handle and was instead revised with a bone cement prosthesis. During the implantation of the intramedullary stems, three patients experienced minor cortical splitting, which was managed with bundling and fixation during the procedure. Immediate stability was attained for all prostheses during surgery, yet postoperative limb shortening did not undergo significant correction. All patients exhibited normal healing of their postoperative incisions. The visual analog scale for limb pain decreased significantly from 8.0±0.8 points before surgery to 1.0±0.4 points three months postoperatively ( t=25.957, P<0.001). By six months after the surgery, none of the patients reported any limb pain. Follow-up data for all 11 patients indicated an average follow-up duration of 25.2±7.5 months (range, 16-36 months), during which limb function improved satisfactorily. The Musculoskeletal Tumor Society (MSTS) score increased from 7.9±1.4 points preoperatively to 20.9±2.7 points at the last follow-up, with this change also being statistically significant ( t=14.229, P<0.001). Imaging evaluations revealed normal lower limb force lines, no rotation or longitudinal displacement of the prosthetic stem, and successful integration with the femur. Conclusion:Personalized intramedullary stems produced through 3D printing demonstrate significant clinical effectiveness in femoral tumor prosthesis revision surgery, making them a viable option for such procedures.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*