LRG1 Contributes to the Pathogenesis of Multiple Kidney Diseases: A Comprehensive Review.

Background: The increasing prevalence of kidney diseases has become a significant public health issue, with a global prevalence exceeding 10%. In order to accurately identify biochemical changes and treatment outcomes associated with kidney diseases, novel methods targeting specific genes have been discovered. Among these genes, leucine-rich α-2 glycoprotein 1 (LRG1) has been identified to function as a multifunctional pathogenic signaling molecule in multiple diseases, including kidney diseases. This study aims to provide a comprehensive overview of the current evidence regarding the roles of LRG1 in different types of kidney diseases. Summary: Based on a comprehensive review, it was found that LRG1 was upregulated in the urine, serum, or renal tissues of patients or experimental animal models with multiple kidney diseases, such as diabetic nephropathy, kidney injury, IgA nephropathy, chronic kidney diseases, clear cell renal cell carcinoma, end-stage renal disease, canine leishmaniosis-induced kidney disease, kidney fibrosis, and aristolochic acid nephropathy. Mechanistically, the role of LRG1 in kidney diseases is believed to be detrimental, potentially through its regulation of various genes and signaling cascades, i.e., fibronectin 1, GPR56, vascular endothelial growth factor (VEGF), VEGFR-2, death receptor 5, GDF15, HIF-1α, SPP1, activin receptor-like kinase 1-Smad1/5/8, NLRP3-IL-1b, and transforming growth factor ß pathway. Key Messages: Further research is needed to fully comprehend the molecular mechanisms by which LRG1 contributes to the pathogenesis and pathophysiology of kidney diseases. It is anticipated that targeted treatments focusing on LRG1 will be utilized in clinical trials and implemented in clinical practice in the future.

Glycolysis and tumor progression promoted by the m6A writer VIRMA via m6A-dependent upregulation of STRA6 in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies, highlighting the urgent need to elucidate the underlying oncogenic mechanisms. VIRMA is a classic isoform of methyltransferases that participates in epigenetic transcriptomic modification in eukaryotic mRNAs. However, the exact roles of VIRMA in PDAC remain unclear. Here, we identified that VIRMA is highly expressed in PDAC, and histone modifications of the promoter may partly account for this dysregulation. Moreover, VIRMA is closely related to glycolysis and poor prognosis in PDAC. We further determined that STRA6 is a direct downstream target of VIRMA in PDAC by RNA sequencing (RNA-seq) and m6A sequencing (m6A-seq). VIRMA is involved in gene expression regulation via 3' UTR targeting of STRA6 mRNA. Furthermore, the m6A reader IGF2BP2 was shown to critically contribute to the stability of STRA6 mRNA. We describe the role of VIRMA in promoting signaling via the STRA6/STAT3 axis, which results in increased levels of HIF-1α, a key activator of glycolysis. In vivo and in vitro experiments reveal that the VIRMA-STRA6-STAT3-HIF-1α axis plays an instrumental role in glycolysis and tumor progression in PDAC. In conclusion, we demonstrate that VIRMA can increase glycolysis in PDAC by upregulating STRA6, a cell surface membrane protein that stimulates the STAT3 pathway, thereby activating HIF-1α and leading to pancreatic cancer malignancy. Overall, our data strongly suggest that the VIRMA-STRA6-STAT3-HIF-1α axis is a viable therapeutic target in PDAC.

The role of autophagy in SIM mediated anti-inflammatory osteoclastogenesis through NLRP3 signaling pathway.

BACKGROUND: Inflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti-inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific mechanism of inflammatory bone loss alleviation by SIM remains to be elucidated. We hypothesized that SIM relieves inflammatory bone loss by modulating autophagy and suppressing the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) signaling pathway. METHODS AND RESULTS: RAW264.7 cells were stimulated by lipopolysaccharide (LPS) after being pretreated with various concentrations of SIM. Osteoclast (OC) differentiation, formation and activity were evaluated by tartrate-resistant acid phosphatase staining, F-actin ring staining and bone resorption pit assays, respectively. We observed autophagosomes by transmission electron microscopy. Then NLRP3 inhibitor MCC950 was used to further explore the corresponding molecular mechanism underlying anti-inflammatory bone resorption, the expression of autophagy-related proteins and NLRP3 signaling pathway factors in pre-OCs were evaluated by western blot analysis, and the expression of OC-specific molecules was analyzed using reverse transcription-quantitative polymerase chain reaction. The results showed that SIM decreased the expression of tumor necrosis factor-α, whereas increased Interleukin-10. In addition, SIM inhibited LPS-induced OC differentiation, formation, bone resorption activity, the level of autophagosomes, and OC-specific markers. Furthermore, SIM significantly suppressed autophagy by downregulating LC3II, Beclin1, ATG7, and NLRP3-related proteins expression while upregulating P62 under inflammatory conditions. CONCLUSIONS: SIM may reduce autophagy secretion to attenuate LPS-induced osteoclastogenesis and the NLRP3 signaling pathway participates in this process, thus providing theoretical basis for the application of this drug in peri-implantitis.

Current knowledge of TNF-α monoclonal antibody infliximab in treating Kawasaki disease: a comprehensive review.

Kawasaki disease (KD), an autoinflammatory disease primarily affecting young children, characterized by consisting of acute systemic vasculitis and coronary artery involvement in severe cases. Intravenous immunoglobulin gamma (IVIG) combined with aspirin therapy is the first-line regimen for the prevention of coronary aneurysms in the acute phase of KD. The etiology and pathogenesis of KD are unclear, but its incidence is increasing gradually, especially in the cases of IVIG-naïve KD and refractory KD. Conventional therapies for refractory KD have unsatisfactory results. At present, infliximab (IFX), a human-murine chimeric monoclonal antibody that specifically blocks tumor necrosis factor-α (TNF-α), has made great progress in the treatment of KD. This review revealed that IFX infusion (5 mg/kg) could effectively modulate fever, reduce inflammation, improve arthritis, diminish the number of plasma exchange, decrease hospitalizations, and prevent the progression of coronary artery lesions. The adverse effects of IFX administration included skin rash, arthritis, respiratory disease, infusion reaction, hepatomegaly, and vaccination-associated complications. But the incidence of these adverse effects is low. The clear optimal application protocol of the application of IFX for either initial combination therapy or salvage therapy in KD is still under investigation. In addition, there are no effective biomarkers to predict IFX resistance. Further multicenter trials with large sample size and long-term follow-up are still needed to validate the clinical efficacy and safety of IFX for IVIG-resistant KD or refractory KD.

The multikinase inhibitor axitinib in the treatment of advanced hepatocellular carcinoma: the current clinical applications and the molecular mechanisms.

Advanced hepatocellular carcinoma (HCC) is a formidable public health problem with limited curable treatment options. Axitinib, an oral tyrosine kinase inhibitor, is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3. This anti-angiogenic drug was found to have promising activity in various solid tumors, including advanced HCC. At present, however, there is no relevant review article that summarizes the exact roles of axitinib in advanced HCC. In this review, 24 eligible studies (seven studies in the ClinicalTrials, eight experimental studies, and nine clinical trials) were included for further evaluation. The included randomized or single-arm phase II trials indicated that axitinib could not prolong the overall survival compared to the placebo for the treatment of advanced HCC, but improvements in progression free survival and time to tumor progression were observed. Experimental studies showed that the biochemical effects of axitinib in HCC might be regulated by its associated genes and affected signaling cascades (e.g. VEGFR2/PAK1, CYP1A2, CaMKII/ERK, Akt/mTor, and miR-509-3p/PDGFRA). FDA approved sorafenib combined with nivolumab (an inhibitor of PD-1/PD-L1) as the first line regimen for the treatment of advanced HCC. Since both axitinib and sorafenib are tyrosine kinase inhibitors as well as the VEGFR inhibitors, axitinib combined with anti-PDL-1/PD-1 antibodies may also exhibit tremendous potential in anti-tumoral effects for advanced HCC. The present review highlights the current clinical applications and the molecular mechanisms of axitinib in advanced HCC. To move toward clinical applications by combining axitinib and other treatments in advanced HCC, more studies are still warranted in the near future.

IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis.

IKKα has been shown to be responsible of multiple pro-tumorigenic functions and therapy resistance independent of canonical NF-κB, but its role in acquired chemotherapy resistance in breast cancer remains unclarified. In this study, we obtained pre-treatment biopsy and post-treatment mastectomy specimens from a retrospective cohort of triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy(NAC) (n = 43). Immunohistochemical methods were used to detect the expression of IKKα before and after NAC, and the relationship between IKKα and the pathologic response to NAC was examined. In addition, we developed a new ADR-resistant MDA-MB-231 cell line(MDA-MB-231/ADR) and analyzed these cells for changes in IKKα expression, the role and mechanisms of the increased IKKα in promoting drug resistance were determined in vitro and in vivo. We demonstrated that the expression of IKKα in residual TNBC tissues after chemotherapy was significantly higher than that before chemotherapy, and was positively correlated with lower pathological reaction. IKKα expression was significantly higher in ADR-resistant TNBC cells than in ADR-sensitive cells, IKKα knockdown results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, IKKα knockdown promotes chemotherapeutic drug-induced tumor cell death in an transplanted tumor mouse model. Functionally, we demonstrated that IKKα knockdown significantly upregulated the expression of cleaved caspase 3 and Bax and inhibited the expression of Bcl-2 upon ADR treatment. Our findings highlighted that IKKα exerts an important and previously unknown role in promoting chemoresistance in TNBC, combining IKKα inhibition with chemotherapy may be an effective strategy to improve treatment outcome in chemoresistant TNBC patients.

The positive relationship between androgen receptor splice variant-7 expression and the risk of castration-resistant prostate cancer: A cumulative analysis.

Background: At present, androgen deprivation therapy (ADT) is still the standard regimen for patients with metastatic and locally advanced prostate cancer (PCa). The level of androgen receptor splice variant-7 (AR-V7) in men with castration-resistant prostate cancer (CRPC) has been reported to be elevated compared with that in patients diagnosed with hormone-sensitive prostate cancer (HSPC). Aim: Herein, we performed a systematic review and cumulative analysis to evaluate whether the expression of AR-V7 was significantly higher in patients with CRPC than in HSPC patients. Methods: The commonly used databases were searched to identify the potential studies reporting the level of AR-V7 in CRPC and HSPC patients. The association between CRPC and the positive expression of AR-V7 was pooled by using the relative risk (RR) with the corresponding 95% confidence intervals (CIs) under a random-effects model. For detecting the potential bias and the heterogeneity of the included studies, sensitivity analysis and subgroup analysis were performed. Publication bias was assessed Egger's and Begg's tests. This study was registered on PROSPERO (ID: CRD42022297014). Results: This cumulative analysis included 672 participants from seven clinical trials. The study group contained 354 CRPC patients, while the other group contained 318 HSPC patients. Pooled results from the seven eligible studies showed that the expression of positive AR-V7 was significantly higher in men with CRPC compared to those with HSPC (RR = 7.55, 95% CI: 4.61-12.35, p < 0.001). In the sensitivity analysis, the combined RRs did not change substantially, ranging from 6.85 (95% CI: 4.16-11.27, p < 0.001) to 9.84 (95% CI: 5.13-18.87, p < 0.001). In the subgroup analysis, a stronger association was detected in RNA in situ hybridization (RISH) measurement in American patients, and those studies were published before 2011 (all p < 0.001). There was no significant publication bias identified in our study. Conclusion: Evidence from the seven eligible studies demonstrated that patients with CRPC had a significantly elevated positive expression of AR-V7. More investigations are still warranted to clarify the association between CRPC and AR-V7 testing. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022297014.

Construction and systematic evaluation of a machine learning-based cuproptosis-related lncRNA score signature to predict the response to immunotherapy in hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is a common malignant cancer with a poor prognosis. Cuproptosis and associated lncRNAs are connected with cancer progression. However, the information on the prognostic value of cuproptosis-related lncRNAs is still limited in HCC. Methods: We isolated the transcriptome and clinical information of HCC from TCGA and ICGC databases. Ten cuproptosis-related genes were obtained and related lncRNAs were correlated by Pearson's correlation. By performing lasso regression, we created a cuproptosis-related lncRNA prognostic model based on the cuproptosis-related lncRNA score (CLS). Comprehensive analyses were performed, including the fields of function, immunity, mutation and clinical application, by various R packages. Results: Ten cuproptosis-related genes were selected, and 13 correlated prognostic lncRNAs were collected for model construction. CLS was positively or negatively correlated with cancer-related pathways. In addition, cell cycle and immune related pathways were enriched. By performing tumor microenvironment (TME) analysis, we determined that T-cells were activated. High CLS had more tumor characteristics and may lead to higher invasiveness and treatment resistance. Three genes (TP53, CSMD1 and RB1) were found in high CLS samples with more mutational frequency. More amplification and deletion were detected in high CLS samples. In clinical application, a CLS-based nomogram was constructed. 5-Fluorouracil, gemcitabine and doxorubicin had better sensitivity in patients with high CLS. However, patients with low CLS had better immunotherapeutic sensitivity. Conclusion: We created a prognostic CLS signature by machine learning, and we comprehensively analyzed the signature in the fields of function, immunity, mutation and clinical application.

Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation.

Emerging evidence shows that the biomechanical environment is required to support cancer stem cells (CSCs), which play a crucial role in drug resistance. However, how mechanotransduction signals regulate CSCs and its clinical significance has remained unclear. Using clinical-practice ultrasound elastography for patients' lesions and atomic force microscopy for surgical samples, we reveal that increased matrix stiffness is associated with poor responses to neoadjuvant chemotherapy, worse prognosis, and CSC enrichment in patients with breast cancer. Mechanically, TAZ activated by biomechanics enhances CSC properties via phase separation with NANOG. TAZ-NANOG phase separation, which is dependent on acidic residues in the N-terminal activation domain of NANOG, promotes the transcription of SOX2 and OCT4. Therapeutically, targeting NANOG or TAZ reduces CSCs and enhances the chemosensitivity in vivo. Collectively, this study demonstrated that the phase separation of a pluripotency transcription factor links mechanical cues in the niche to the fate of CSCs.

Aloe vera for prevention of radiation-induced dermatitis: A systematic review and cumulative analysis of randomized controlled trials.

Background: Aloe vera were frequently reported to reduce the risk of radiation-induced dermatitis (RID), but the quantitative results from all the relevant studies were not presently available. This study sought to conduct a cumulative analysis to better clarify the preventive effects of aloe vera in RID. Methods: MEDLINE (PubMed), Cochrane, EMBASE, PsychINFO, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang Database were utilized for identifying the eligible randomized controlled trials (RCTs) without language restrictions, up to March 2022. The pooled incidence of RID was conducted by the Relative risk (RR) with its 95% confidence interval (CI) through the STATA software under a random-effects model. This systematic review and cumulative analysis were registered on PROSPERO (ID: CRD42022335188). Results: Fourteen RCTs met our predefined inclusion criteria, enrolling 1,572 participants (mean age: 46.5-56 years). The cumulative results revealed that patients pretreated with aloe vera were associated with a significantly lower risk of RID compared to those without aloe vera usage (RR = 0.76, 95% CI: 0.67-0.88, p < 0.001; heterogeneity: I 2 = 79.8%, p < 0.001). In the subgroup analysis, the pooled incidence of Grade 2-4, Grade 2, and Grade 3 RID was also dramatically lower in the group of aloe vera as compared to the placebo group [RR = 0.44 (0.27, 0.74), 0.58 (0.36, 0.94), and 0.27 (0.12, 0.59) in Grade 2-4, Grade 2, and Grade 3, respectively]. However, in regard to Grade 4 RID, the combined RR indicated that the incidence of RID was comparable between aloe vera and the control group (RR = 0.13, 95% CI: 0.02-1.01, p = 0.051; heterogeneity: I 2 = 0.0%, p = 0.741). The sensitivity analyses showed that there was no substantial change in the new pooled RR after eliminating anyone of the included study. Conclusion: The current cumulative analysis revealed that patients pretreated with aloe vera were less likely to suffer from RID than the controls without using aloe vera. Based on this finding, the prophylactic application of aloe vera might significantly reduce the incidence of RID, especially in Grade 2 and Grade 3 RID. Further large-sample multicenter RCTs are still warranted to confirm these findings and for better clinical application.

Craniopharyngioma resection and aneurysm clipping performed simultaneously by pure endoscopic endonasal approach: A case report and literature review.

Craniopharyngioma is one of the most challenging issues for neurosurgeons as a brain tumor. Among the approaches of neurosurgery, in comparison to craniotomy, the endoscopic endonasal approach (EEA) has risen in popularity over the last two decades; unruptured intracranial aneurysms are relatively commonly found in the general population. The EEA as a new paradigm in the treatment of aneurysm has been reported to successfully clip dozens of cases of intracranial aneurysm. However, when reviewing the domestic and foreign literature, it appeared that cases of craniopharyngioma complicated with intracranial aneurysm purely treated by EEA have not been reported so far. In the present study, the published literature regarding endoscopic endonasal surgery for craniopharyngioma and intracranial aneurysms was reviewed, accompanied with a case of craniopharyngioma complicated with intracranial aneurysm, both of which were simultaneously treated by EEA.

MicroRNA-21: A Critical Pathogenic Factor of Diabetic Nephropathy.

Diabetic nephropathy (DN), one of the most common and intractable microvascular complications of diabetes, is the main cause of terminal renal disease globally. MicroRNA-21 (miR-21) is a kind of miRNA early identified in human circulation and tissues. Mounting studies have demonstrated that miR-21 plays an important role in the development and progression of DN. This collaborative review aimed to present a first attempt to capture the current evidence on the relationship between miR-21 and DN. After a systematic search, 29 relevant studies were included for comprehensively and thoroughly reviewing. All these eligible studies reported that miR-21 was up-regulated in DN, whether in serum or renal tissues of human or animal models. MiR-21 exhibited its pathogenic roles in DN by forming a complex network with targeted genes (e.g. MMP-9, Smad7, TIMP3, Cdk6, FOXO1, IMP3, and MMP2) and the signaling cascades (e.g. Akt/TORC1 signaling axis, TGF-ß/NF-κB signaling pathways, TGF-ß/SMAD pathway, CADM1/STAT3 signaling, and AGE-RAGE regulatory cascade), which resulted in epithelial-to-mesenchymal transition, extracellular matrix deposition, cytoskeletal remodeling, inflammation, and fibrosis. This review highlights that miR-21 is a pivotal pathogenic factor in the development of DN. It may serve as an attractive potential diagnostic, prognostic, and predictive biomarker for DN in clinical practice after further confirmation of the clinicopathological features and molecular mechanisms of miR-21-mediated DN.

Feasibility and advantages analyses of wedge resection without mesentery detached approach applied to closure of loop ileostomy.

OBJECTIVES: To evaluate the feasibility and advantages of wedge resection plus transverse suture without mesentery detached approach applied to loop ileostomy closure by analyzing the surgical data and the incidence of postoperative complications of patients undergoing this procedure. METHODS: We performed a retrospective analysis of the hospitalization data of patients who underwent ileostomy closure surgery and met the research standards from January 2017 to April 2021 in Guangxi Medical University Cancer Hospital; all surgeries were performed by the same surgeon. The perioperative data were statistically analyzed by grouping. RESULTS: In total, 65 patients were enrolled in this study, with 12 in the wedge resection group, 35 in the stapler group, and 18 in the hand suture group. There was no significant difference in operation time between the wedge resection group and stapler group (P > 0.05), but both groups had shorter operation time than that in the hand suture group (P < 0.05). The postoperative exhaustion time of wedge resection group was earlier than that of the others, and cost of surgical consumables in the wedge resection group was significantly lower than that in the stapler group, all with statistically significant differences (P < 0.05). By contrast, there were no statistically significant differences in postoperative complication incidences among the three groups. CONCLUSIONS: The wedge resection plus transverse suture without mesentery detached approach is safe and easy for closure of loop ileostomy in selected patients, and the intestinal motility recovers rapidly postoperatively. It costs less surgical consumables, and is particularly suitable for the currently implemented Diagnosis-Related Groups payment method.

Cerebrospinal fluid leak management in anterior basal skull fractures secondary to head trauma.

OBJECTIVE: To summarize the presentation, diagnosis, and management of cerebrospinal fluid (CSF) leaks in the setting of traumatic anterior skull base fracture. METHODS: Wide literature research has been performed as well as the authors' own clinical experience has been summarized. RESULTS: Articles from the most recent 30 years have been reviewed and a typical case of our own has been presented. Based on the most updated evidence, a treatment algorithm for CSF leaks has been proposed. CONCLUSION: Anterior skull base fracture accounts for about 4% of all head injuries and CSF leaks is a complication that commonly presents with clear fluid emanating from the nasal passage. A positive beta-2-transferrin study is highly specific for diagnosis, while thin-slice CT scanning and MRI cisternography are also useful tools. The majority of the CSF leaks tend to be resolved spontaneously, and conservative management is attempted first with or without the augmentation of a lumbar drain. Surgical management mainly includes open surgery and endoscopic surgery, which have their own pros and cons.

Influence of Pre-treatment Saliva Microbial Diversity and Composition on Nasopharyngeal Carcinoma Prognosis.

Background: The human microbiome has been reported to mediate the response to anticancer therapies. However, research about the influence of the oral microbiome on nasopharyngeal carcinoma (NPC) survival is lacking. We aimed to explore the effect of oral microbiota on NPC prognosis. Methods: Four hundred eighty-two population-based NPC cases in southern China between 2010 and 2013 were followed for survival, and their saliva samples were profiled using 16s rRNA sequencing. We analyzed associations of the oral microbiome diversity with mortality from all causes and NPC. Results: Within- and between-community diversities of saliva were associated with mortality with an average of 5.29 years follow-up. Lower Faith's phylogenetic diversity was related to higher all-cause mortality [adjusted hazard ratio (aHR), 1.52 (95% confidence interval (CI), 1.06-2.17)] and NPC-specific mortality [aHR, 1.57 (95% CI, 1.07-2.29)], compared with medium diversity, but higher phylogenetic diversity was not protective. The third principal coordinate (PC3) identified from principal coordinates analysis (PCoA) on Bray-Curtis distance was marginally associated with reduced all-cause mortality [aHR, 0.85 (95% CI, 0.73-1.00)], as was the first principal coordinate (PC1) from PCoA on weighted UniFrac [aHR, 0.86 (95% CI, 0.74-1.00)], but neither was associated with NPC-specific mortality. PC3 from robust principal components analysis was associated with lower all-cause and NPC-specific mortalities, with HRs of 0.72 (95% CI, 0.61-0.85) and 0.71 (95% CI, 0.60-0.85), respectively. Conclusions: Oral microbiome may be an explanatory factor for NPC prognosis. Lower within-community diversity was associated with higher mortality, and certain measures of between-community diversity were related to mortality. Specifically, candidate bacteria were not related to mortality, suggesting that observed associations may be due to global patterns rather than particular pathogens.

Zoledronic acid inhibits osteoclastogenesis and bone resorptive function by suppressing RANKL­mediated NF­κB and JNK and their downstream signalling pathways.

Targeting excessive osteoclast differentiation and activity is considered a valid therapeutic approach for osteoporosis. Zoledronic acid (ZOL) plays a pivotal role in regulating bone mineral density. However, the exact molecular mechanisms responsible for the inhibitory effects of ZOL on receptor activator of nuclear factor (NF)­κB ligand (RANKL)­induced osteoclast formation are not entirely clear. The present study aimed to investigate the role of ZOL in osteoclast differentiation and function, and to determine whether NF­κB and mitogen­activated protein kinase, and their downstream signalling pathways, are involved in this process. RAW264.7 cells were cultured with RANKL for differentiation into osteoclasts, in either the presence or absence of ZOL. Osteoclast formation was observed by tartrate­resistant acid phosphatase staining and bone resorption pit assays using dentine slices. The expression of osteoclast­specific molecules was analysed using reverse transcription­quantitative polymerase chain reaction and western blotting assays to deduce the molecular mechanisms underlying the role of ZOL in osteoclastogenesis. The results showed that ZOL significantly attenuated osteoclastogenesis and bone resorptive capacity in vitro. ZOL also suppressed the activation of NF­κB and the phosphorylation of c­Jun N­terminal kinase. Furthermore, it inhibited the expression of the downstream factors c­Jun, c­Fos and nuclear factor of activated T cells c1, thereby decreasing the expression of dendritic cell­specific transmembrane protein and other osteoclast­specific markers. In conclusion, ZOL may have therapeutic potential for osteoporosis.

Proliferating cell nuclear antigen clamp associated factor, a potential proto-oncogene with increased expression in malignant gastrointestinal tumors.

Gastrointestinal (GI) cancers, including malignancies in the gastrointestinal tract and accessory organs of digestion, represent the leading cause of death worldwide due to the poor prognosis of most GI cancers. An investigation into the potential molecular targets of prediction, diagnosis, prognosis, and therapy in GI cancers is urgently required. Proliferating cell nuclear antigen (PCNA) clamp associated factor (PCLAF), which plays an essential role in cell proliferation, apoptosis, and cell cycle regulation by binding to PCNA, is a potential molecular target of GI cancers as it contributes to a series of malignant properties, including tumorigenesis, epithelial-mesenchymal transition, migration, and invasion. Furthermore, PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer. In addition to GI cancers, PCLAF is also involved in other types of cancers and autoimmune diseases. Several pivotal pathways, including the Rb/E2F pathway, NF-κB pathway, and p53-p21 cascade, are implicated in PCLAF-mediated diseases. PCLAF also contributes to some diseases through dysregulation of the p53 pathway, WNT signal pathway, MEK/ERK pathway, and PI3K/AKT/mTOR signal cascade. This review mainly describes in detail the role of PCLAF in physiological status and GI cancers. The signaling pathways involved in PCLAF are also summarized. Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.

Open biopsy with posterior instrumentation followed by anterolateral approach for removal of an uncommon tumor in the cervical spine.

The conventional treatment for the resection of cervical spinal tumors comprises anterior, posterior, and combined surgical approaches. However, these approaches have certain limitations when tumors invade the vertebrae, vertebral artery, or spinal nerves. Herein, we report an interesting case where a 45-year-old patient was admitted for neck pain. An invasive cervical spinal tumor was discovered and approached in two stages: stage 1 was open biopsy with posterior instrumentation, which was followed by stage 2 with an anterolateral approach for definitive surgical resection. A series of preoperative tests including angiography as well as a balloon occlusion test of the vertebral artery facilitated stage 2 surgical planning for gross total resection of the tumor while minimizing surgical complications.

Dietary patterns and risk of nasopharyngeal carcinoma: a population-based case-control study in southern China.

BACKGROUND: Dietary factors, such as consumption of preserved foods, fresh vegetables, and fruits, have been linked to the risk of nasopharyngeal carcinoma (NPC). However, little is known about associations between dietary patterns and the risk of NPC in NPC-endemic areas. OBJECTIVES: We aimed to evaluate whether dietary patterns are associated with NPC risk. METHODS: We studied 2554 newly diagnosed NPC patients aged 20-74 y living in 3 endemic regions of southern China, and 2648 population-based controls frequency-matched to case patients by age, sex, and region, between 2010 and 2014. Dietary components were derived from food frequency data in adulthood and adolescence using principal component analysis. Four dietary components were identified and highly similar in adulthood and adolescence. We used multivariable unconditional logistic regression to calculate ORs with 95% CIs for the association between dietary patterns and NPC risk. RESULTS: Compared with the lowest quartile, individuals in the highest quartile of the "plant-based factor" in adulthood had a 52% (OR: 0.48; 95% CI: 0.38, 0.59) decreased risk of NPC, and those in the highest quartile of the "animal-based factor" had a >2-fold (OR: 2.26; 95% CI: 1.85, 2.77) increased risk, with a monotonic dose-response trend (P-trend < 0.0001). Similar but weaker associations were found in adolescence. High intakes of the "preserved-food factor" were associated with increased NPC risk in both periods, although stronger associations were found in adolescence. Results from joint analysis and sensitivity analyses indicated that dietary factors in adulthood might be more stable and robust predictors of NPC risk than those in adolescence. CONCLUSIONS: Our results deliver compelling evidence that plant- and animal-based dietary factors are associated with NPC risk, and provide more insights on the associations of diets and cancer risk that may assist healthy diet recommendations.