Loss of walking independence one year after primary total hip arthroplasty for osteonecrosis of the femoral head: incidence and risk prediction model.

BACKGROUND: Assessment of postoperative ambulation in osteonecrosis of the femoral head (ONFH) patients treated with total hip arthroplasty (THA) is limited. This study aimed to define the incidence and risk factors for losing walking independence (LWI) at one-year postoperatively in patients with ONFH undergoing primary THA, and to establish and validate a predictive nomogram. METHODS: This was a retrospective analysis of prospective collected data from patients admitted to a tertiary referral hospital with ONFH who underwent primary unilateral THA from October 2014 to March 2018. The Functional Independence Measure-Locomotion scale was used to quantify walking independence and was documented at a one-year continuous postoperative follow-up, which classified patients with a final score below 6 as LWI. Multivariate logistic regression identified independent risk factors for LWI, and a predictive nomogram was constructed based on the analysis results. The stability of the model was assessed using patients from April 2018 to April 2019 as an external validation set. RESULTS: 1152 patients were enrolled in the study, of which 810 were used in the training cohort and the other 342 for the validation cohort. The incidence of LWI was 5.93%. Multivariate analysis revealed that age 62 years or older (odd ratio (OR) = 2.37, 95% confidence interval (CI) 1.07-5.24), Charlson's comorbidity index 3 or higher (OR = 3.64, 95% CI 1.09-12.14), Association Research Circulation Osseous stage IV (OR = 2.16, 95% CI 1.03-4.54), reduced femoral offset (OR = 2.41, 95% CI 1.16-5.03), and a higher controlling nutritional status score (OR = 1.14, 95% CI 1.01-1.30) were independent risk factors of LWI. The nomogram had a concordance index of 0.773 and a Brier score of 0.049 in the training set, with corrected values of 0.747 and 0.051 after internal validation. The receiver-operating characteristic curve, calibration curve, Hosmer-Lemeshow test, and decision curve analysis all performed well in both the training and validation cohorts. CONCLUSIONS: This study reported a 5.93% incidence of LWI and established a risk prediction model in patients undergoing THA for ONFH, supporting targeted screening and intervention to assist surgeons in assessing ambulation capacity and managing rehabilitation.

Genetic association and functional implications of TLR4 rs1927914 polymorphism on colon cancer risk.

BACKGROUND: Colon cancer remains a major health concern worldwide, with genetic factors playing a crucial role in its development. Toll-like receptors (TLRs) has been implicated in various cancers, but their role in colon cancer is not well understood. This study aims to identify functional polymorphisms in the promoter and 3'UTR regions of TLRs and evaluate their association with colon cancer susceptibility. METHODS: We conducted a case-control study involving 410 colon cancer patients and 410 healthy controls from the Chinese population. Genotyping of polymorphisms in TLR3, TLR4, TLR5 and TLR7 was performed using PCR-RFLP and TaqMan MGB probes. Using logistic regression analysis, we evaluated the association of TLRs polymorphisms and the susceptibility to colon cancer. To understand the biological implications of the TLR4 rs1927914 polymorphism, we conducted functional assays, including luciferase reporter assay and electrophoretic mobility shift assay (EMSA). RESULTS: Our results demonstrated that the G-allele of the TLR4 rs1927914 polymorphism is significantly associated with a decreased risk of colon cancer (OR = 0.68, 95%CI = 0.50-0.91). Stratified analysis showed that TLR4 rs1927914 AG or GG genotype contributed to a decreased risk of colon cancer among younger individuals (OR = 0.52, 95%CI = 0.34-0.81), males (OR = 0.58, 95%CI = 0.38-0.87), non-smokers (OR = 0.58, 95%CI = 0.41-0.83) and non-drinker with OR (95%CI) of 0.66 (0.46-0.93). Functional assays demonstrated that in HCT116 and LOVO colon cancer cells, the luciferase activity driven by the TLR4 promoter with the rs1927914A allele was 5.43 and 2.07 times higher, respectively, compared to that driven by the promoter containing the rs1927914G allele. Electrophoretic mobility shift assay (EMSA) results indicated that the rs1927914G allele enhanced transcription factor binding. Using the transcription factor prediction tool, we found that the G allele facilitates binding of the repressive transcription factor Oct1, while the A allele does not. CONCLUSION: The TLR4 rs1927914 polymorphism influence the susceptibility to colon cancer, with the G allele offering a protective effect through modulation of gene expression. These insights enhance our understanding of the genetic determinants of colon cancer risk and highlight TLR4 as a promising target for cancer prevention strategies.

Duration of surgical antibiotic prophylaxis and surgical site infection in orthopaedic surgery: A prospective cohort study.

BACKGROUND: The optimal duration for surgical antibiotic prophylaxis (SAP) for preventing surgical site infection (SSI) in orthopaedic surgeries remains poorly supported by high-level evidence. This study aimed to assess the association between SAP duration and the occurrence of SSI within one year postoperatively. METHODS: This prospective cohort study was based on the database from Surgical Site Infection Surveillance and Improvement Project (SISIP) of a tertiary orthopaedic university hospital from October 2014 to December 2020. The main outcome was SSI, defined according to the CDC/NHSN criteria, determined by review of index hospitalization medical records, microbiology laboratory reports, and readmission records for SSI treatment within one-year after discharge. Adjusted Generalized additive models (GAMs) were performed to assess the relationships between SAP duration and SSI, determined the cut-off point of SAP duration, and estimate the relative contribution of each included variable, across the overall cohort and the three subgroups (open fracture, closed fracture, and non-traumatic group). Multivariable logistic regression models were used to estimate the association between prolonging SAP duration based on the cut-off point and SSI. RESULTS: There were 37,046 patients (55.1% male) included, with the overall SSI incidence of 2.35% (871/37,046). In adjusted GAMs, no statistically significant relationships were observed in overall cohort and open or closed group (P>0.05), but a nonlinear relationship was exhibited non-traumatic group (P=0.03); the cut-off point were 2.4 days for overall cohort and 3.6 days (open), 2.6 days (closed), 1.1 days (non-trauma) for three subgroups. In adjusted logistic regression, prolonging SAP duration did not demonstrate a statistically significant protective effect in overall cohort (aOR=0.868; 95% CI, 0.746-1.011) and three groups (open: aOR=0.867; 95% CI, 0.668-1.124; closed: aOR=0.925; 95% CI, 0.754-1.135; non-trauma: aOR=1.184; 95% CI, 0.832-1.683). The relative contribution ranks of SAP duration were 21st overall among 34 factors, 14th for open fractures, 28th for closed fractures, and 3rd for non-traumatic group among 33 factors. CONCLUSION: Prolonged postoperative SAP duration has no protective effect against SSI in orthopaedic surgery. Our findings support current guidelines against the practice of continuing SAP postoperatively.

Risk factors of preoperative deep vein thrombosis in patients with non-traumatic osteonecrosis of the femoral head.

PURPOSE: This study aims to identify independent risk factors for preoperative lower extremity deep venous thrombosis (DVT) in patients with non-traumatic osteonecrosis of the femoral head (NONFH), and to develop a prediction nomogram. METHODS: Retrospective analysis of prospectively collected data on patients presenting with non-traumatic osteonecrosis of the femoral head between October 2014 and April 2019 was conducted. Duplex ultrasonography (DUS) was routinely used to screen for preoperative DVT of bilateral lower extremities. Data on demographics, chronic comorbidities, preoperative characteristics, and laboratory biomarkers were collected. Univariate analyses and multivariate logistic regression analyses were used to identify the independent risk factors associated with DVT which were combined and transformed into a nomogram model. RESULT: Among 2824 eligible patients included, 35 (1.24%) had preoperative DVT, including 15 cases of proximal thrombosis, and 20 cases of distal thrombosis. Six independent risk factors were identified to be associated with DVT, including Sodium ≤ 137 mmol/L (OR = 2.116, 95% confidence interval [CI]: 1.036-4.322; P = 0.040), AGE ≥ 49 years (OR = 7.598, 95%CI: 1.763-32.735; P = 0.008), D-Dimer > 0.18 mg/L (OR = 2.351, 95%CI: 1.070-5.163; P = 0.033), AT III ≤ 91.5% (OR = 2.796, 95%CI: 1.387-5.634; P = 0.006), PLT ≥ 220.4*109 /L (OR = 7.408, 95%CI: 3.434-15.981; P = 0.001) and ALB < 39 g/L (OR = 3.607, 95%CI: 1.084-12.696; P = 0.042). For the nomogram model, AUC was 0.845 (95%CI: 0.785-0.906), and C-index was 0.847 with the corrected value of 0.829 after 1000 bootstrapping validations. Moreover, the calibration curve and DCA exhibited the tool's good prediction consistency and clinical practicability. CONCLUSION: These epidemiologic data and the nomogram may be conducive to the individualized assessment, risk stratification, and development of targeted prevention programs for preoperative DVT in patients with NONFH.

CSPG4P12 polymorphism served as a susceptibility marker for esophageal cancer in Chinese population.

BACKGROUND: Chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) has been implicated in the pathogenesis of various cancers. This study aimed to evaluate the association of the CSPG4P12 polymorphism with esophageal squamous cell carcinoma (ESCA) risk and to explore the biological impact of CSPG4P12 expression on ESCA cell behavior. METHODS: A case-control study was conducted involving 480 ESCA patients and 480 healthy controls to assess the association between the rs8040855 polymorphism and ESCA risk. The CSPG4P12 rs8040855 genotype was identified using the TaqMan-MGB probe method. Logistic regression model was used to evaluate the association of CSPG4P12 SNP with the risk of ESCA by calculating the odds ratios (OR) and 95% confidence intervals (95%CI ). The effects of CSPG4P12 overexpression on cell proliferation, migration, and invasion were examined in ESCA cell lines. Co-expressed genes were identified via the CBioportal database, with pathway enrichment analyzed using SangerBox. The binding score of CSPG4P12 to P53 was calculated using RNA protein interaction prediction (RPISeq). Additionally, Western Blot analysis was performed to investigate the impact of CSPG4P12 overexpression on the P53/PI3K/AKT signaling pathway. RESULTS: The presence of at least one rs8040855 G allele was associated with a reduced susceptibility to ESCA compared to the CC genotype (OR = 0.51, 95%CI = 0.28-0.93, P = 0.03). Stratification analysis revealed that the CSPG4P12 rs8040855 C allele significantly decreased the risk of ESCA among younger individuals (≤ 57 years) and non-drinkers (OR = 0.31, 95%CI = 0.12-0.77, P = 0.01; OR = 0.42, 95%CI=0.20-0.87, P = 0.02, respectively). CSPG4P12 expression was found to be downregulated in ESCA tissues compared to adjacent normal tissues. Overexpression of CSPG4P12 in ESCA cells inhibited their proliferation, migration, and invasion capabilities. Furthermore, Western Blot analysis indicated that CSPG4P12 overexpression led to a reduction in PI3K and p-AKT protein expression levels. P53 silencing rescues the inhibitory effect of CSPG4P12 on p-AKT. CONCLUSION: The CSPG4P12 rs8040855 variant is associated with reduced ESCA risk and the overexpression of CSPG4P12 inhibited the migration and invasion of ESCA cells by P53/PI3K/AKT pathway. These findings suggest that CSPG4P12 may serve as a novel biomarker for ESCA susceptibility and a potential target for therapeutic intervention.

The effect of distal locking mode on postoperative mechanical complications in intertrochanteric fractures: a retrospective cohort study of five hundred and seven patients.

PURPOSE: The optimal choice of distal locking modes remains a subject due to limited available data, and therefore, this study aims to investigate the relationship between distal locking mode and postoperative mechanical complications in an intertrochanteric fracture (ITF) population who underwent closed reduction and intramedullary fixation with a PFNA-II. METHODS: Patients aged 65 years or older who underwent surgery with PFNA-II fixation in a university teaching hospital between January 2020 and December 2021 were potentially eligible. Based on the distal locking mode, patients were classified into static, dynamic, and limited dynamic groups, among which the differences were tested using univariate analysis. Multivariate logistic regression was used to examine whether the distal locking mode was independently associated with the risk of postoperative one year mechanical complications, adjusting for covariates and potential confounders. Subgroup analyses were performed to evaluate the robustness of the findings. RESULT: Among 507 eligible patients, 33 (6.5%) developed postoperative mechanical complications. In the univariate analysis, sex (P = 0.007), fracture type (P = 0.020), LAT Parker ratio (P = 0.023), and lateral femoral (P = 0.003) wall showed that the differences were significant. Compared to the static group, the limited dynamic group and the dynamic group showed higher odds of postoperative mechanical complications (OR = 3.314, 95% CI: 1.215-9.041; and OR = 3.652, 95% CI: 1.451-9.191, respectively). These associations were robust across a series of analyses, including adjusting for confounders and subgroup analyses. CONCLUSION: Using a distal non-static locking mode significantly increases the risk of postoperative mechanical complications, and static locking could be a preferable option when treating an intertrochanteric fracture.

Comparison of outcomes after total hip arthroplasty between patients with osteonecrosis of the femoral head in Association Research Circulation Osseous stage III and stage IV: a five-year follow-up study.

BACKGROUND: No large cohort study has evaluated the surgical outcomes of THA between different stages of ONFH patients. This study aimed to compare the surgical outcomes of ONFH patients who underwent THA in ARCO stage III versus IV, in terms of operative parameters, one-year hip function assessments and postoperative at least five-year complications, to inform optimized management of ONFH. METHOD: From our prospectively collected database, 876 patients undergoing THA between October 2014 and April 2017 were analyzed and divided into ARCO stage III group (n = 383) and ARCO stage IV group(n = 493). Details of demographics, medical record information, adverse events and clinical scores of both groups were collected and compared. Proper univariate analysis was used for the analysis. RESULT: There were no statistically significant differences in baseline characteristics between the two groups. Compared to ARCO stage IV patients, ARCO stage III patients showed a shorter operative time (p < 0.01), less bleeding (p < 0.01), fewer one-year readmissions (p = 0.026) and complications (p = 0.040), and significantly higher HHS (p < 0.01) one year after THA. In addition, ARCO stage IV patients seem more likely to suffer prosthesis dislocation (p = 0.031). CONCLUSION: Although ARCO stage IV patients in the study cohorts appeared to suffer more one-year complications, no significant difference was observed at long-term follow-up. Enhanced clinical guidance on preventing early prosthesis dislocation may help improve the prognosis of final-stage ONFH patients.

One-year unplanned readmission after total hip arthroplasty in patients with osteonecrosis of the femoral head: rate, causes, and risk factors.

BACKGROUND: The primary objectives of this study were to focus on one - year unplanned readmissions after THA in ONFH patients and to investigate rates, causes, and independent risk factors. METHODS: Between October 2014 and April 2019, eligible patients undergoing THA were enrolled and divided into unplanned readmission within one year and no readmission in this study. All unplanned readmissions within 1 year of discharge were reviewed for causes and the rate of unplanned readmissions was calculated. Demographic information, ONFH characteristics, and treatment-related variables of both groups were compared and analysed. RESULTS: Finally, 41 out of 876 patients experienced unplanned readmission. The readmission rate was 1.83% in 30 days 2.63% in 90 days, and 4.68% in 1 year. Prosthesis dislocation was always the most common cause at all time points studied within a year. The final logistic regression model revealed that higher risks of unplanned readmission were associated with age > 60 years (P = 0.001), urban residence (P = 0.001), ARCO stage IV (P = 0.025), and smoking (P = 0.033). CONCLUSIONS: We recommend the introduction of a strict smoking cessation program prior to surgery and the development of comprehensive management strategies, especially for the elderly and end-stage ONFH patients, and pay more attention to preventing prosthesis dislocation in the early days after surgery.

Association of preoperative nutritional status evaluated by the controlling nutritional status score with walking independence at 180 days postoperatively: a prospective cohort study in Chinese older patients with hip fracture.

BACKGROUND: Malnutrition is significantly associated with unfavorable outcomes, but there is little high-level evidence to elucidate the association of malnutrition with losing walking independence (LWI) after hip fracture surgery. This study aimed to assess the association between preoperative nutritional status evaluated by the Controlling Nutritional Status (CONUT) score and walking independence at 180 days postoperatively in Chinese older hip fracture patients. METHODS: This prospective cohort study included 1958 eligible cases from the SSIOS database. The restricted cubic spline was used to assess the dose-effect relationship between the CONUT score and the recovery of walking independence. Propensity score matching was performed to balance potential preoperative confounders, and multivariate logistic regression analysis was applied to assess the association between malnutrition and LWI with perioperative factors for further adjustment. Furthermore, inverse probability treatment weighting and sensitivity analyses were performed to test the robustness of the results and the Fine and Gray hazard model was applied to adjust the competing risk of death. Subgroup analyses were used to determine potential population heterogeneity. RESULTS: The authors found a negative relationship between the preoperative CONUT score and recovery of walking independence at 180 days postoperatively, and that moderate-to-severe malnutrition evaluated by the CONUT score was independently associated with a 1.42-fold (95% CI, 1.12-1.80; P =0.004) increased risk of LWI. The results were overall robust. And in the Fine and Gray hazard model, the result was still statistically significant despite the apparent decrease in the risk estimate from 1.42 to 1.21. Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, American Society of Anesthesiologists score, Charlson's comorbidity index, and surgical delay ( P for interaction < 0.05). CONCLUSION: Preoperative malnutrition is a significant risk factor for LWI after hip fracture surgery, and nutrition screening on admission would generate potential health benefits.

Autogenous bone-guided induced membrane technique in closed/small-sized open high-energy fractures in benign inflammatory environment: a case series.

OBJECTIVE: Infection and nonunion are the two most challenging issues for high-energy fractures. This study aimed to explore the clinical effect of benign inflammation-cultivated bone growth activity in the treatment of closed/small-sized open and high-energy fractures. METHODS: This study is a case series of closed/small-sized open and high-energy fractures of the lower limbs treated at our hospital from April 2009 to February 2017. All patients underwent debridement and external fixation in the early stage, followed by internal fixation in the second stage. After the operation, fracture healing was monitored by X-ray, and early-stage knee function training was initiated. Also, bone grafting was performed to stimulate the healing reaction, eliminating the atrophic nonunion factors. RESULTS: The operation in all 75 cases was carried out after the inflammatory responses completely subsided, leading to secondary wound healing. Bony union appeared in 71 patients who did not suffer from any pain and could stand up and walk without any restriction. Among them, 68 patients could flex their knee > 100°, and three patients had knee flexion ranging from 80 to 100°. No infections occurred after the second operation. CONCLUSION: This two-stage treatment for high-energy fractures could avoid the damage caused by excessive inflammatory responses that occurred following early-stage one-time internal fixation. This method protected benign inflammatory-callus reactions induced by the primary injury and utilized the advantages of closed reduction in AO fixation with open reduction, thereby avoiding potential infection and nonunion caused by one-time fixation during the early stage.

Three Potential Tumor Markers Promote Metastasis and Recurrence of Colorectal Cancer by Regulating the Inflammatory Response: ADAM8, LYN, and S100A9.

Metastasis and recurrence are major causes of colorectal cancer (CRC) death, but their molecular mechanisms are unclear. In this study, genes associated with CRC metastasis and recurrence were identified by weighted gene coexpression network analysis, selecting the top 25% most variant genes in the dataset GSE33113. By average linkage hierarchical clustering, a total of 21 modules were generated. One key module was identified as the most relevant to the prognosis of CRC. Gene Ontology analysis indicated that genes associated with tumor metastasis and recurrence in this module were significantly enriched in inflammatory biological functions. Functional analysis was performed on the key module, and candidate hub genes (ADAM8, LYN, and S100A9) were screened out by expression and survival analysis. In summary, the three core genes identified in this study could greatly improve our understanding of CRC metastasis and recurrence. The results also provide a theoretical basis for the use of three core genes (ADAM8, LYN, and S100A9) as a combined marker for early diagnosis, which could benefit CRC patients.

The genetic and epigenetic regulation of CD55 and its pathway analysis in colon cancer.

Background: CD55 plays an important role in the development of colon cancer. This study aims to evaluate the expression of CD55 in colon cancer and discover how it is regulated by transcriptional factors and miRNA. Methods: The expression of CD55 was explored by TIMER2.0, UALCAN, and Human Protein Atlas (HPA) databases. TRANSFAC and Contra v3 were used to predict the potential binding sites of transcription factors in the CD55 promoter. TargetScan and starBase v2.0 were used to predict the potential binding ability of miRNAs to the 3' untranslated region (3'UTR) of CD55. SurvivalMeth was used to explore the differentially methylated sites in the CD55 promoter. Western blotting was used to detect the expression of TFCP2 and CD55. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were performed to determine the targeting relationship of TFCP2, NF-κB, or miR-27a-3p with CD55. CD55-related genes were explored by constructing a protein-protein interaction (PPI) network and performing pathway analysis by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: CD55 was highly expressed in colon cancer tissues. The mRNA and protein expression levels of TFCP2 were reduced by si-TFCP2. NF-κB mRNA was obviously reduced by NF-κB inhibitor and increased by NF-κB activator. CD55 protein was also inhibited by miR-27a-3p. Dual-luciferase reporter assays showed that after knocking down TFCP2 or inhibiting NF-κB, the promoter activity of CD55 was decreased by 21% and 70%, respectively; after activating NF-κB, the promoter activity of CD55 increased by 2.3 times. As TFCP2 or NF-κB binding site was mutated, the transcriptional activity of CD55 was significantly decreased. ChIP assay showed that TFCP2 and NF-κB combined to the promoter of CD55. The luciferase activity of CD55 3'UTR decreased after being co-transfected with miR-27a-3p mimics and increased by miR-27a-3p antagomir. As the miR-27a-3p binding site was mutated, we did not find any significant effect of miR-27a-3p on reporter activity. PPI network assay revealed a set of CD55-related genes, which included CFP, CFB, C4A, and C4B. GO and KEGG analyses revealed that the target genes occur more frequently in immune-related pathways. Conclusion: Our results indicated that CD55 is regulated by TFCP2, NF-κB, miR-27a-3p, and several immune-related genes, which in turn affects colon cancer.

Inspiration for the prevention and treatment of neuropsychiatric disorders: New insight from the bone-brain-axis.

Bone is the main supporting structure of the body and the main organ involved in body movement and calcium and phosphorus metabolism. Recent studies have shown that bone is also a potential new endocrine organ that participates in the physiological and pathophysiological processes of the cardiovascular, digestive, and endocrine systems through various bioactive cytokines secreted by bone cells and bone marrow. Bone-derived active cytokines can also directly act on the central nervous system and regulate brain function and individual behavior. The bidirectional regulation of the bone-brain axis has gradually attracted attention in the field of neuroscience. This paper reviews the regulatory effects of bone-derived active cytokines and bone-derived cells on individual brain function and brain diseases, as well as the occurrence and development of related neuropsychiatric diseases. The central regulatory mechanism function is briefly introduced, which will broaden the scope for mechanistic research and help establish prevention and treatment strategies for neuropsychiatric diseases based on the bone-brain axis.

XPF -673C>T variation is associated with the susceptibility to breast cancer.

PURPOSE: XPF variations might decrease the DNA repair capacity and further contribute to cancer development. This study aimed to investigate the association of XPF polymorphisms with risk of developing breast cancer. METHODS: TCGA, the Human Protein Atlas and Kaplan-Meier plotter were used to analyze the expression of XPF in breast cancer tissues and its effect on the survival of breast cancer patients. The expression of XPF in breast cancer tissues was detected by qRT-PCR. This case-control study included 467 breast cancer patients and 467 healthy controls. The genotype of genetic variation was detected by polymerase chain reaction restriction fragment length polymorphism. Odds ratios and 95 % confidence intervals were calculated. Correlations between XPF variation and clinicopathological parameters were assessed through Kendall's Tau-b test. The relationship between XPF gene function variation and XPF gene expression was analyzed by GTEx. RESULTS: The expression of XPF in breast cancer tissues is higher than that in normal tissues. Breast cancer patients with high XPF expression have a higher relapse free survival rate (HR = 0.88, 95 % CI = 0.80-0.97), but have no effect on the overall survival rate (logrank P = 0.28). XPF -673C > T variant can reduce the risk of breast cancer patients (OR = 0.35, 95 %CI = 0.20-0.63 for codominant mode; OR = 0.66, 95 %CI = 0.51-0.85 for dominant model; OR = 0.40, 95 %CI = 0.23-0.70 for recessive model). The XPF 11985 GG genotype reduced the risk of early breast cancer (OR = 0.49, 95 %CI = 0.24-0.97), but not the risk of advanced breast cancer (OR = 1.20, 95 % CI = 0.58-2.48). XPF 11985A > G variant can also reduce the risk of ERBB2 expression in patients (OR = 0.50, 95 %CI = 0.27-0.94). There is no correlation between XPF -673C > T/XPF11985A > G variants and ER and PR. XPF -673C > T variant can reduce XPF expression (P < 0.05). CONCLUSIONS: Genetic variations of XPF gene may affect its expression and the risk of breast cancer in the Chinese population.

Phlorizin from sweet tea inhibits the progress of esophageal cancer by antagonizing the JAK2/STAT3 signaling pathway.

Phlorizin, an important member of the dihydrochalcone family, has been widely used as a Chinese Traditional Medicine for treatment of numerous diseases. The present study aimed to investigate the potential therapeutic effects of phlorizin on esophageal cancer. Phlorizin, extracted from sweet tea, was used to treat esophageal cancer cells. Cell proliferation, migration and invasion were determined using Cell Counting Kit­8 and colony formation assays, and wound healing and Transwell assays, respectively. RNA sequencing and bioinformatics analysis was used to investigate the potential mechanism of phlorizin in the development of esophageal cancer. Fluorescent staining and flow cytometry was used to measure the level of apoptosis. The expression level of the proteins, P62/SQSTM1 and LC3 Ð†/II, and the effect of phlorizin on the JAK2/STAT3 signaling pathway was detected using western blot analysis. The results demonstrated that phlorizin could inhibit cell proliferation, migration and invasion. Bioinformatics analysis showed that phlorizin might be involved in pleiotropic effects, such as the 'JAK/STAT signaling pathway' (hsa04630), 'MAPK signaling pathway'(hsa04010) and 'apoptosis' (hsa04210). It was also confirmed that phlorizin promoted apoptosis and inhibited autophagy in the esophageal cancer cells. Notably, phlorizin might inhibit the proteins in the JAK/STAT signaling pathway, which would affect cancer cells. Taken together, the present data showed that phlorizin inhibited the progression of esophageal cancer by antagonizing the JAK2/STAT3 signaling pathway.

Integration of transcriptomics and metabolomics reveals anlotinib-induced cytotoxicity in colon cancer cells.

BACKGROUND: Mounting evidences suggested that anlotinib exhibits effective anti-tumor activity in various cancer types, such as lung cancer, glioblastoma and medullary thyroid cancer. However, its function in colon cancer remains to be further revealed. METHODS: Colon cancer cells (HCT-116) were treated with or without anlotinib. Transcript and metabolite data were generated through RNA sequencing and liquid chromatography-tandem mass spectrometry, respectively. The integrated analysis transcriptomics and metabolomics was conducted using R programs and online tools, including ClusterProfiler R program, GSEA, Prognoscan and Cytoscape. RESULTS: We found that differentially expressed genes (DEGs) were mainly involved in metabolic pathways and ribosome pathway. Structural maintenance of chromosome 3 (SMC3), Topoisomerase II alpha (TOP2A) and Glycogen phosphorylase B (PYGB) are the most significant DEGs which bring poor clinical prognosis in colon cancer. The analysis of metabolomics presented that most of the differentially accumulated metabolites (DAMs) were amino acids, such as L-glutamine, DL-serine and aspartic acid. The joint analysis of DEGs and DAMs showed that they were mainly involved in protein digestion and absorption, ABC transporters, central carbon metabolism, choline metabolism and Gap junction. Anlotinib affected protein synthesis and energy supporting of colon cancer cells by regulating amino acid metabolism. CONCLUSIONS: Anlotinib has a significant effect on colon cancer in both transcriptome and metabolome. Our research will provide possible targets for colon cancer treatment using anlotinib.

XAB2 TagSNP Is Associated with the Risk of Gastric Cancer in Chinese Population: A Case-Control Study.

XAB2 protein (xeroderma pigmentosum group A-binding protein 2) plays a significant role in the nucleotide excision repair pathway. Polymorphisms in the XAB2 gene may have an effect on the capability of DNA repair and further contribute to the risk of developing various cancers. In order to investigate the relationship between XAB2 genetic variants and the risk of gastric cancer, we performed a hospital-based case-control study. XAB2 tagSNPs were selected and then genotyped by iPlex Gold Genotyping Assay and Sequenom MassArray. By performing logistic regression analysis, odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association of XAB2 tagSNPs with the risk of gastric cancer. Our results showed that XAB2 rs794078AA genotype was associated with a significantly lower risk of gastric cancer compared with GG genotype with OR (95% CI) of 0.33 (0.12-0.91). Stratified analysis indicated a significantly decreased risk for gastric cancer among smokers with rs794078AA genotype compared with nonsmokers with GG genotype (OR = 0.11, 95% CI = 0.01-0.91, p = 0.040). The gene-gene interactions by multifactor dimensionality reduction (MDR) showed that tagSNP rs794078 was the best predictive element for gastric cancers (Testing Bal. Acc = 51.68%, p = 0.055, cross-validation consistency = 9). Therefore, the XAB2 tagSNP rs794078 may play an important role in the development of gastric cancer.

Impact of Genetic Variation in TLR4 3'UTR on NSCLC Genetic Susceptibility.

Toll-like receptors (TLRs) are expressed not only in immune cells but also in a variety of tumor cells. Single-nucleotide polymorphisms (SNPs) located in the TLRs' promoter or the 3' untranslated region may affect gene expression by affecting the activity of the promoter or regulating the binding of mRNA to miRNA. This study aimed to investigate the association of the SNPs in TLR genes with the susceptibility to NSCLC. This case-control study involved 700 lung cancer patients and 700 healthy controls. All individuals were genotyped for all selected SNPs in TLR genes using polymerase chain reaction (PCR) test-based restriction fragment length polymorphism (PCR-RFLP) and TaqMan SNP genotyping assay. The association of genetic variations in TLRs with the susceptibility to NSCLC was evaluated by unconditional logistic regression with OR (95% CI). After evaluating transcriptional factor or miRNA binding capability by bioinformatics methods, six TLRs were identified for further analysis. We did not find that TLR3 rs5743303, TLR4 rs1927914, TLR4 rs11536891, TLR5 rs1640816, and TLR7 rs3853839 were associated with NSCLC risk (P > 0.05). Our data showed that TLR4 rs7869402 C > T polymorphism reduced the risk of NSCLC with OR (95% CI) of 0.63 (0.45-0.89). When stratified by gender and age, the individuals carrying at least one rs7869402T allele significantly decreased the NSCLC risk among males (OR = 0.58, 95% CI = 0.38-0.87) and among youngsters (OR = 0.43, 95% CI = 0.27-0.69). Smoking stratification analysis showed that the rs7869402T allele-containing genotype reduced the risk of NSCLC with OR (95% CI) of 0.50 (0.29-0.87) among smokers but not among nonsmokers (P > 0.05). When the individuals were classed by the pathological type, we found that the rs7869402T-containing genotype was associated with the risk of adenocarcinoma (OR = 0.62, 95% CI = 0.41-0.92) but not with that of squamous cell carcinoma (OR = 0.71, 95% CI = 0.44-1.13) and other types (OR = 0.23, 95% CI = 0.03-1.70). Compared with the TLR4 Ars1927914-Crs7869402-Trs11536891 haplotype, the Grs1927914-Trs7869402-Trs11536891 haplotype was associated with a decreased risk for developing NSCLC with OR (95% CI) of 0.57 (0.41-0.80). These results indicated that the TLR4 rs7869402 variation affects the genetic susceptibility to NSCLC.

Xenon produces rapid antidepressant- and anxiolytic-like effects in lipopolysaccharide-induced depression mice model.

Onset delay of current antidepressants is always the most significant limitation for the treatment of depression. More attention has been given to the glutamate acid system for developing fast-onset antidepressants. Xenon, acting as a well-known N-methyl-D-aspartate receptors antagonist, has been widely used clinically as anesthetics and was reported to exert antidepressant-like effects in rats under normal condition. The robust and rapid-acting antidepressant- and anxiolytic-like activities of xenon through the use of depression rodent model are still elusive. By using lipopolysaccharide-induced depression mice models, the present study aimed to evaluate the fast-acting antidepressant-like effects of xenon pretreatment. Behavioral tests, mainly including open-field test, novelty-suppressed feeding test, sucrose preference test, tail suspension test, and forced swimming test, were conducted respectively. Our results showed that both xenon gas and xenon-rich saline pretreatment intraperitoneally produced significant antidepressant- and anxiolytic-like activities in mice under normal condition. Further, xenon gas pretreatment (intraperitoneally) rapidly blocked lipopolysaccharide-induced depression- and anxiety-like behaviors of mice. These findings provide direct evidence that xenon could produce fast-onset antidepressant- and anxiolytic-like activities, which highlights the possibility to develop xenon as a promising fast-acting drug for treatment of depression, anxiety, and even other stress-related diseases.