Osteosarcoma neutrophil extracellular trap network-associated gene recurrence and metastasis model.

Osteosarcoma (OS) is the most common malignancy in children and adolescents and has a high probability of recurrence and metastasis. A growing number of studies have shown that neutrophil extracellular traps (NETs) are strongly associated with cancer metastasis, but in osteosarcoma, genes associated with NETs that promote osteosarcoma recurrence and metastasis remain to be explored. We systematically investigated the gene expression patterns of NETs in OS samples from the GEO database. NETs molecular typing was evaluated based on NETs expression profiles, and the association between NETs molecular subtypes and immune microenvironment and metastatic features were explored. Ultimately, we constructed a signature model and column line graph associated with metastasis prediction and screened possible potential drugs for metastatic osteosarcoma. We established two different molecular subtypes of NETs, which showed significant differences in metastatic status, metastasis time, tumor immune microenvironment, and biological effects. We also constructed a NETs-related gene metastasis signature(NRGMS) to assess the expression pattern of NETs in patients to predict metastatic recurrence in osteosarcoma patients. We screened for TOMM40 and FH associated with metastatic recurrence in osteosarcoma patients. Overall, this study constructs a predictive model for osteosarcoma metastasis of NETs-related genes, which is expected to provide new insights into the metastasis of osteosarcoma.

Subcutaneously Engineered Decalcified Bone Matrix Xenografts Promote Bone Repair by Regulating the Immune Microenvironment, Prevascularization, and Stem Cell Homing.

Immunoregulatory and vascularized microenvironments play an important role in bone regeneration; however, the precise regulation for vascularization and inflammatory reactions remains elusive during bone repair. In this study, by means of subcutaneous preimplantation, we successfully constructed demineralized bone matrix (DBM) grafts with immunoregulatory and vascularized microenvironments. According to the current results, at the early time points (days 1 and 3), subcutaneously implanted DBM grafts recruited a large number of pro-inflammatory M1 macrophages with positive expression of CD68 and iNOS, while at the later time points (days 7 and 14), these inflammatory cells gradually subsided, accompanying increased presence of anti-inflammatory M2 macrophages with positive expression of CD206 and Arg-1, indicating a gradually enhanced anti-inflammatory microenvironment. At the same time, the gradually increased angiogenesis was observed in the DBM grafts with implantation time. In addition, the positive cells of CD105, CD73, and CD90 were observed in the inner region of the DBM grafts, implying the homing of mesenchymal stem cells. The repair results of cranial bone defects in a rat model further confirmed that the subcutaneous DBM xenografts at 7 days significantly improved bone regeneration. In summary, we developed a simple and novel strategy for bone regeneration mediated by anti-inflammatory microenvironment, prevascularization, and endogenous stem cell homing.

[Experimental study on the stimulation effect of temperature and capsaicin on oral mucosa of rats].

PURPOSE: This study evaluated the effect of hot etching with two acid solutions on the surface topography and bond strength of zirconia. METHODS: Firstly, twenty-four pieces of zirconia with a size of 10 mm×10 mm×2 mm and 20 pieces of zirconia with a size of 3 mm×3 mm×2 mm were prepared. Then pieces were divided into four groups, and dealt with separately according to the following groups: no treatment (group A), sandblasting (group B), hot etching with HCl(group C), hot etching with HF(group D). Finally, the surface topography and bond strength were tested by atomic force microscopy(AFM), scanning electron microscope(SEM), X-ray diffraction(XRD) and universal testing machine, etc. Statistical analysis of the experimental data was performed with SPSS 26.0 software package. The final results of XRD were analyzed using MDI Jade 6 combined with Origin 2019 software. RESULTS: Groups C and D produced completely different topographical changes on the surface of zirconia than group B. Obvious interfacial cracks were observed in group B. Group D achieved the highest roughness value (78.17±4.94) nm and highest shear bond strength (25.09±4.09) MPa. CONCLUSIONS: Compared with HCl, hot etching with HF could achieve more uniform and dense porous morphology, greater roughness and shear bond strength. There were no obvious cross-section interfacial cracks and crystal phase transformations on the surface of zirconia.

A systematic review and meta-analysis: clinical outcomes of recurrent pregnancy failure resulting from preimplantation genetic testing for aneuploidy.

Background: Preimplantation genetic testing for aneuploidy (PGT-A) is an emerging technology that aims to identify euploid embryos for transfer, reducing the risk of embryonic chromosomal abnormalities. However, the clinical benefits of PGT-A in recurrent pregnancy failure (RPF) patients, particularly in young RPF patients, remains uncertain. Objective and rationale: This meta-analysis aimed to determine whether RPF patients undergoing PGT-A had better clinical outcomes compared to those not undergoing PGT-A, thus assessing the value of PGT-A in clinical practice. Search methods: We systematically searched PubMed, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Database for Chinese Technical Periodicals (VIP) from 2002 to 2022. Thirteen published studies involving 930 RPF patients screened using PGT-A and over 1,434 RPF patients screened without PGT-A were included in this meta-analysis. Clinical outcomes were evaluated based on embryo transfers after PGT-A (n=1,015) and without PGT-A (n=1,799). Clinical outcomes: The PGT-A group demonstrated superior clinical outcomes compared to the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) group. The PGT-A group had a significantly higher implantation rate (IR) (RR=2.01, 95% CI: [1.73; 2.34]), clinical pregnancy rate (CPR) (RR=1.53, 95% CI: [1.36; 1.71]), ongoing pregnancy rate (OPR) (RR=1.76, 95% CI: [1.35; 2.29]), live birth rate (LBR) (RR=1.75, 95% CI: [1.51; 2.03]), and significantly lower clinical miscarriage rate (CMR) (RR=0.74, 95% CI: [0.54; 0.99]). Subgroup analysis based on patient age (under 35 years and 35 years or older) showed that both PGT-A subgroups had significantly better CPR (P<0.01) and LBR (P<0.05) values compared to the IVF/ICSI groups. Summary: This meta-analysis demonstrates that PGT-A in RPF patients, is associated with improved clinical outcomes, including higher IR, CPR, OPR, and LBR values, and lower CMR compared to the IVF/ICSI group. These findings support the positive clinical application of PGT-A in RPF patients. Systematic Review Registration: http://INPLASY.com, identifier INPLASY 202320118.

A Positive Feedback Loop of E2F4-Mediated Activation of MNX1 Regulates Tumour Progression in Colorectal Cancer.

Purpose: Colorectal cancer (CRC) is the 3rd most prevalent malignant tumour globally. Although significant strides have been made in diagnosis and treatment, its prognosis at the moment remains unpromising. Therefore, there is an urgent and desperate need to identify novel biomarkers of CRC and evaluate its mechanism of tumourigenesis and development. Methods: JASPAR and RNAinter databases are used to analyze target genes associated with colorectal cancer. Western blotting, q-PCR and immunohistochemistry et, al. were used to detect the level of MNX1 in patients with colorectal cancer, and Chip-PCR was used to detect the targeted binding ability of E2F4 and MNX1. The cells and animal models overexpressed MNX1 and E2F4 were constructed by shRNA transfection. Results: Herein, MNX1 was highly expressed and linked to favourable overall survival curves in colorectal cancer. The functional assay revealed that MNX1 overexpression could promote proliferation, migration, and invasion of CRC cells. Based on the prediction of the JASPAR and RNAinter databases, the transcription factor, E2F4, was bound to the MNX1 promoter region. The Chromatin Immunoprecipitation (ChIP) assay verified the interactions between MNX1 and E2F4 in CRC. Additionally, we found that sh-E2F4 markedly downregulated the MNX1 levels and reduced CRC progression in vivo and in vitro, which reversed MNX1 overexpression. Conclusion: Therefore, our research discovered that E2F4-mediated abnormal MNX1 expression promotes CRC progression and could become a novel diagnostic or therapeutic target of CRC.

BMP6 participates in the pathogenesis of adolescent idiopathic scoliosis by regulating osteopenia.

Adolescent idiopathic scoliosis (AIS) is a complex disease characterized by three-dimensional structural deformities of the spine. Its pathogenesis is associated with osteopenia. Bone-marrow-derived mesenchymal stem cells (BMSCs) play an important role in bone metabolism. We detected 1919 differentially expressed mRNAs and 744 differentially expressed lncRNAs in BMSCs from seven patients with AIS and five patients without AIS via high-throughput sequencing. Multiple analyses identified bone morphogenetic protein-6 (BMP6) as a hub gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS. BMP6 expression was found to be decreased in AIS and its knockdown in human BMSCs significantly altered the degree of osteogenic differentiation. Additionally, CAP1-217 has been shown to be a potential upstream regulatory molecule of BMP6. We showed that CAP1-217 knockdown downregulated the expression of BMP6 and the osteogenic differentiation of BMSCs. Simultaneously, knockout of BMP6 in zebrafish embryos significantly increased the deformity rate. The findings of this study suggest that BMP6 is a key gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS via the CAP1-217/BMP6/RUNX2 axis.

Research progress on the regulation of bone marrow stem cells by noncoding RNAs in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in young women, but its pathogenesis remains unclear. The primary pathogenic factors contributing to its development include genetics, abnormal bone metabolism, and endocrine factors. Bone marrow stem cells (BMSCs) play a crucial role in the pathogenesis of AIS by regulating its occurrence and progression. Noncoding RNAs (ncRNAs) are also involved in the pathogenesis of AIS, and their role in regulating BMSCs in patients with AIS requires further evaluation. In this review, we discuss the relevant literature regarding the osteogenic, chondrogenic, and lipogenic differentiation of BMSCs. The corresponding mechanisms of ncRNA-mediated BMSC regulation in patients with AIS, recent advancements in AIS and ncRNA research, and the importance of ncRNA translation profiling and multiomics are highlighted.

Construction of 3D-Bioprinted cartilage-mimicking substitute based on photo-crosslinkable Wharton's jelly bioinks for full-thickness articular cartilage defect repair.

Three-dimensional (3D) bioprinted cartilage-mimicking substitutes for full-thickness articular cartilage defect repair have emerged as alternatives to in situ defect repair models. However, there has been very limited breakthrough in cartilage regeneration based on 3D bioprinting owing to the lack of ideal bioinks with printability, biocompatibility, bioactivity, and suitable physicochemical properties. In contrast to animal-derived natural polymers or acellular matrices, human-derived Wharton's jelly is biocompatible and hypoimmunogenic with an abundant source. Although acellular Wharton's jelly can mimic the chondrogenic microenvironment, it remains challenging to prepare both printable and biologically active bioinks from this material. Here, we firstly prepared methacryloyl-modified acellular Wharton's jelly (AWJMA) using a previously established photo-crosslinking strategy. Subsequently, we combined methacryloyl-modified gelatin with AWJMA to obtain a hybrid hydrogel that exhibited both physicochemical properties and biological activities that were suitable for 3D bioprinting. Moreover, bone marrow mesenchymal stem cell-loaded 3D-bioprinted cartilage-mimicking substitutes had superior advantages for the survival, proliferation, spreading, and chondrogenic differentiation of bone marrow mesenchymal stem cells, which enabled satisfactory repair of a model of full-thickness articular cartilage defect in the rabbit knee joint. The current study provides a novel strategy based on 3D bioprinting of cartilage-mimicking substitutes for full-thickness articular cartilage defect repair.

Catheter ablation of ventricular premature depolarizations originating from the mid interventricular septum: Significance of electrocardiographic morphology for predicting origin.

BACKGROUND: Ventricular premature depolarizations (VPDs) originating from the mid interventricular septum (IVS) adjacent to the atrioventricular annulus between the His bundle and the coronary sinus ostium (mid IVS VPDs) have not been characterized. OBJECTIVE: The aim of this study was to investigate the electrophysiological characteristics of mid IVS VPDs. METHODS: Thirty-eight patients with mid IVS VPDs were enrolled. VPDs were divided into different types according to precordial transition of the electrocardiogram (ECG) and QRS morphology in lead V1. RESULTS: Four types of VPDs were divided. The precordial transition zone appeared earlier and earlier from types 1 to 4. The notch in lead V1 moved gradually backward, and its amplitude gradually became higher, resulting in the transition from left to right bundle branch block morphology in lead V1 from types 1 to 4. Based on activation and pace mapping, ablation response, and 3830 electrode pacing morphology in the mid IVS, the 4 types of ECG morphology corresponded to an origin in the right endocardial side, right/mid intramural region, left intramural region, and left endocardial side of the mid IVS, respectively. An intramural origin was identified for 50% of VPDs. Eighty-nine percent of mid IVS VPDs could be eliminated. Bilateral ablation (waiting for delayed efficacy) or bipolar ablation was sometimes needed for intramural VPDs. CONCLUSION: Mid IVS VPDs were found to have unique electrophysiological characteristics. The ECG characteristics of mid IVS VPDs were important in terms of prediction of its exact origin, the choice of ablation method, and the likelihood of treatment being successful.

Regeneration of articular cartilage defects: Therapeutic strategies and perspectives.

Articular cartilage (AC), a bone-to-bone protective device made of up to 80% water and populated by only one cell type (i.e. chondrocyte), has limited capacity for regeneration and self-repair after being damaged because of its low cell density, alymphatic and avascular nature. Resulting repair of cartilage defects, such as osteoarthritis (OA), is highly challenging in clinical treatment. Fortunately, the development of tissue engineering provides a promising method for growing cells in cartilage regeneration and repair by using hydrogels or the porous scaffolds. In this paper, we review the therapeutic strategies for AC defects, including current treatment methods, engineering/regenerative strategies, recent advances in biomaterials, and present emphasize on the perspectives of gene regulation and therapy of noncoding RNAs (ncRNAs), such as circular RNA (circRNA) and microRNA (miRNA).

PECAM1 plays a role in the pathogenesis and treatment of bone metastases.

Bone is the third most common metastatic site for all primary tumors, the common primary focus of bone metastases include breast cancer, prostate cancer, and so on. And the median survival time of patients with bone metastases is only 2-3 years. Therefore, it is urgent to develop new targets to diagnose and treat bone metastases. Based on two data sets GSE146661 and GSE77930 associated with bone metastases, it was found that 209 genes differentially expressed in bone metastases group and control group. PECAM1 was selected as hub-gene for the follow-up research after constructing protein-protein interaction (PPI) network and enrichment analysis. Moreover, q-PCR analysis verified that the expression of PECAM1 decreased in bone metastatic tumor tissues. PECAM1 was believed to be possibly related to the function of osteoclasts, we knocked down the expression of PECAM1 with shRNA in lymphocytes extracted from bone marrow nailed blood. The results indicated that sh-PECAM1 treatment could promote osteoclast differentiation, and the sh-PECAM1-treated osteoclast culture medium could significantly promote the proliferation and migration of tumor cells. These results suggested that PECAM1 may be a potential biomarker for the diagnosis and treatment of bone metastases of tumor.

Photobiomodulation provides neuroprotection through regulating mitochondrial fission imbalance in the subacute phase of spinal cord injury.

Increasing evidence indicates that mitochondrial fission imbalance plays an important role in delayed neuronal cell death. Our previous study found that photobiomodulation improved the motor function of rats with spinal cord injury. However, the precise mechanism remains unclear. To investigate the effect of photobiomodulation on mitochondrial fission imbalance after spinal cord injury, in this study, we treated rat models of spinal cord injury with 60-minute photobiomodulation (810 nm, 150 mW) every day for 14 consecutive days. Transmission electron microscopy results confirmed the swollen and fragmented alterations of mitochondrial morphology in neurons in acute (1 day) and subacute (7 and 14 days) phases. Photobiomodulation alleviated mitochondrial fission imbalance in spinal cord tissue in the subacute phase, reduced neuronal cell death, and improved rat posterior limb motor function in a time-dependent manner. These findings suggest that photobiomodulation targets neuronal mitochondria, alleviates mitochondrial fission imbalance-induced neuronal apoptosis, and thereby promotes the motor function recovery of rats with spinal cord injury.

Potential targets and mechanisms of photobiomodulation for spinal cord injury.

As a classic noninvasive physiotherapy, photobiomodulation, also known as low-level laser therapy, is widely used for the treatment of many diseases and has anti-inflammatory and tissue repair effects. Photobiomodulation has been shown to promote spinal cord injury repair. In our previous study, we found that 810 nm low-level laser therapy reduced the M1 polarization of macrophages and promoted motor function recovery. However, the mechanism underlying this inhibitory effect is not clear. In recent years, transcriptome sequencing analysis has played a critical role in elucidating the progression of diseases. Therefore, in this study, we performed M1 polarization on induced mouse bone marrow macrophages and applied low-level laser therapy. Our sequencing results showed the differential gene expression profile of photobiomodulation regulating macrophage polarization. We analyzed these genes using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Networks of protein-protein interactions and competing RNA endogenous networks were constructed. We found that photobiomodulation inhibited STAT3 expression through increasing the expression of miR-330-5p, and that miR-330-5p binding to STAT3 inhibited STAT3 expression. Inducible nitric oxide synthase showed trends in changes similar to the changes in STAT3 expression. Finally, we treated a mouse model of spinal cord injury using photobiomodulation and confirmed that photobiomodulation reduced inducible nitric oxide synthase and STAT3 expression and promoted motor function recovery in spinal cord injury mice. These findings suggest that STAT3 may be a potential target of photobiomodulation, and the miR-330-5p/STAT3 pathway is a possible mechanism by which photobiomodulation has its biological effects.

Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic osteoarthropathy characterized by the progressive degeneration of articular cartilage and synovial inflammation. Early OA clinical treatments involve intra-articular injection of glucocorticoids, oral acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), which are used for anti-inflammation and pain relief. However, long-term use of these agents will lead to inevitable side effects, even aggravate cartilage loss. At present, there are no disease-modifying OA drugs (DMOADs) yet approved by regulatory agencies. Polarization regulation of synovial macrophages is a new target for OA treatment. Inhibiting M1 polarization and promoting M2 polarization of synovial macrophages can alleviate synovial inflammation, relieve joint pain and inhibit articular cartilage degradation, which is a promising strategy for OA treatment. In this study, we describe the molecular mechanisms of macrophage polarization and its key role in the development of OA. Subsequently, we summarize the latest progress of strategies for OA treatment through macrophage reprogramming, including small molecule compounds (conventional western medicine and synthetic compounds, monomer compounds of traditional Chinese medicine), biomacromolecules, metal/metal oxides, cells, and cell derivatives, and interprets the molecular mechanisms, hoping to provide some information for DMOADs development.

Correlative increasing expressions of KIF5b and Nav1.7 in DRG neurons of rats under neuropathic pain conditions.

Nav1.7, one of tetrodotoxin-sensitive voltage-gated sodium channels, mainly expressed in the small diameter dorsal root ganglion (DRG) neurons. The expression and accumulation on neuronal membrane of Nav1.7 increased following peripheral tissue inflammation or nerve injury. However, the mechanisms for membrane accumulation of Nav1.7 remained unclear. We report that KIF5b, a highly expressed member of the kinesin-1 family in DRGs, promoted the translocation of Nav1.7 to the plasma membrane in DRG neurons of the rat. Following nociceptive behaviors in rats induced by peripheral spared nerve injury (SNI), synchronously increased KIF5b and Nav1.7 expressions were observed in DRGs. Immunohistochemistry staining demonstrated the co-expressions of KIF5b and Nav1.7 in the same DRG neurons. Immunoprecipitation experiments further confirmed the interactions between KIF5b and Nav1.7. Moreover, intrathecal injections of KIF5b shRNA moderated the SNI-induced both mechanical and thermal hyperalgesia. The rescued analgesic effects also alleviated SNI-induced anxiety-like behaviors. In sum, KIF5b was required for the membrane localizations of Nav1.7, which suggests a novel mechanism for the trafficking of Nav1.7 involved in neuropathic pain.

Electrocardiographic and electrophysiological characteristics of ventricular arrhythmias from the right bundle branch of the moderator band.

BACKGROUND: There are little data on ventricular arrhythmias (VAs) originating from the right bundle branch (RBB) of the moderator band (MB) (MB-RBB VAs) in a cohort of patients. OBJECTIVE: The purpose of this study was to investigate the electrocardiographic and electrophysiological characteristics of MB-RBB VAs. METHODS: Sixteen patients with MB-RBB VAs and 5 patients with right ventricular (RV) anterior papillary muscle (APM) VAs (RV-APM VAs) were studied under the guidance of intracardiac echocardiography. RESULTS: The MB-RBB VAs group demonstrated a typical left bundle branch block pattern with left superior axis deviation and a narrower QRS complex during VAs (P < .001) as compared with the RV-APM VAs group. Furthermore, the MB-RBB VAs group had a shorter rS interval, a sharper slope of the S wave downstroke without notching in leads V1 and V2, and a shorter r wave duration in lead V2. A leading RBB potential at the target during VAs was observed for all patients in the MB-RBB VAs group, which was also present during sinus rhythm for all patients, except for 2 with RBB block at baseline. Ablation of the leading RBB potential effectively eliminated the arrhythmia. In the RV-APM VAs group, no Purkinje potential at the target was identified in any patient during VAs. CONCLUSION: QRS morphology of MB-RBB VAs is characterized by a typical left bundle branch block pattern with a relatively narrow QRS complex, short r wave and rS durations, and a sharp S wave downstroke without notching in leads V1 and V2. Mapping and ablation of the leading RBB potential are effective in eliminating VAs.

Malignant transformation of rectal endometriosis: Preoperative diagnosis by endorectal ultrasound guided biopsy.

The prevalence of malignant transformation of endometriotic lesions is estimated between 0.3% and 1%. Malignant transformations of endometriosis occur in the colorectum is rarer, accounting for 0.25%. Because the malignant transformation of colorectal endometriosis rarely involves mucosa, it is difficult to obtain abnormal tissue by routine endoscopic biopsy. In this case, we evaluated a patient with a rectal mass by endorectal ultrasound (ERUS) and performed endorectal ultrasound-guided biopsy (EGB). Malignant transformations of endometriosis were confirmed by histological result. For patients with rectal tumors but with negative findings on colonoscopy and biopsy, ERUS and EGB contribute to preoperative diagnosis.

Clinical and imaging associations for non-ketotic hyperglycemic chorea: a case-control study.

Background: The non-ketotic hyperglycemic chorea (NKHC) was a rare complication for patients with diabetes mellitus, but not been well studied. In the present research, we aimed to investigate the clinical and imaging characteristics of NKHC and explore the potential association. Methods: We performed a case-control study with patients diagnosed as NKHC. The patients with group of NKHC were retrospectively recruited, while the matched group were set to screened patients with diabetes mellitus but no NKHC at a 1:3 ratio. The clinical and imaging data were collected for all the participants of the two groups. Firstly, Correlation analysis was conducted to test the difference of all the variables between the NKHC group and matched group. Then, the putative associated factors for NKHC were further identified. Results: Eleven men and 9 women with NKHC and 60 matched participants were analyzed. The mean age of the NKHC group was 68.5 ± 14.9 years. Participants with NKHC were more likely to have a higher glycosylated hemoglobin (HbA1c) level (13 ± 2.82 vs. 10.57 ± 2.71, P<0.001), and a higher frequency of renal dysfunction (estimated glomerular filtration rates <60 ml/min/1.73m2) (55% vs. 20%, P=0.005). Logistic regression analyses showed that both higher HbA1c and renal dysfunction were significantly correlated with NKHC. Conclusion: A higher value of HbA1c and renal dysfunction may be associated with the occurrence of NKHC.

Effects of Infection-Induced Fever and the Interaction with IL6 rs1800796 Polymorphism on the Prognosis of Breast Cancer.

BACKGROUND: Previous studies have found that acute febrile infection may decrease the risk of breast cancer. Meanwhile, it is well known that interleukin-6 (IL6) played dual roles in the tumor microenvironment. Fever may stimulate IL6 production, and IL6 rs1800796 also influences the expression of IL6. However, the impact of fever and its interaction with IL6 rs1800796 on breast cancer survival remains to be explored. METHODS: This was a prospective cohort study of 4,223 breast cancer patients. Exposures were pre-/postdiagnostic infection-induced fever and rs1800796 polymorphism. The endpoints were overall survival (OS) and progression-free survival (PFS). Adjusted hazard ratios were obtained using multivariate Cox proportional hazards regression models. RESULTS: Compared with women without prediagnostic fever, the adjusted hazard ratio (HR) of progression for those with prediagnostic fever was 0.81 (95% CI, 0.66-0.99), particularly for the CC genotype of IL6 rs1800796 (HR, 0.53; 95% CI, 0.36-0.79). OS was also better (HR, 0.59; 95% CI, 0.36-0.99) among women with the CC genotype exposed to prediagnostic fever, accompanied by a significant interaction (P = 0.021). Postdiagnostic fever conferred better PFS for breast cancer (HR, 0.72; 95% CI, 0.52-1.00). Irrespective of the genotype of IL6, lymph node-positive women with postdiagnostic fever (HR, 0.57; 95% CI, 0.37-0.89) had a lower risk of progression than lymph node-negative women (HR, 1.12; 95% CI, 0.70-1.79). CONCLUSIONS: Infection-induced fever was beneficial to breast cancer survival, particularly for women who were the CC genotype of IL6 rs1800796 or node positive. IMPACT: This study provides new insight into the roles of infection-induced fever as a potential prognostic marker and therapy regimen for breast cancer.