Predicting colorectal cancer risk: a novel approach using anemia and blood test markers.

Background and objectives: Colorectal cancer remains an important public health problem in the context of the COVID-19 (Corona virus disease 2019) pandemic. The decline in detection rates and delayed diagnosis of the disease necessitate the exploration of novel approaches to identify individuals with a heightened risk of developing colorectal cancer. The study aids clinicians in the rational allocation and utilization of healthcare resources, thereby benefiting patients, physicians, and the healthcare system. Methods: The present study retrospectively analyzed the clinical data of colorectal cancer cases diagnosed at the Affiliated Hospital of Guilin Medical University from September 2022 to September 2023, along with a control group. The study employed univariate and multivariate logistic regression as well as LASSO (Least absolute shrinkage and selection operator) regression to screen for predictors of colorectal cancer risk. The optimal predictors were selected based on the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. These predictors were then utilized in constructing a Nomogram Model for predicting colorectal cancer risk. The accuracy of the risk prediction Nomogram Model was assessed through calibration curves, ROC curves, and decision curve analysis (DCA) curves. Results: Clinical data of 719 patients (302 in the case group and 417 in the control group) were included in this study. Based on univariate logistic regression analysis, there is a correlation between Body Mass Index (BMI), red blood cell count (RBC), anemia, Mean Corpuscular Volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), Red Cell Distribution Width-Standard Deviation (RDW-SD), and the incidence of colorectal cancer. Based on the findings of multivariate logistic regression analysis, the variables of BMI and RBC exhibit a decrease, while anemia and PLT demonstrate an increase, all of which are identified as risk factors for the occurrence of colorectal cancer. LASSO regression selected BMI, RBC, anemia, and PLT as prediction factors. LASSO regression and multivariate logistic regression analysis yielded the same results. A nomogram was constructed based on the 4 prediction factors identified by LASSO regression analysis to predict the risk of colorectal cancer. The AUC of the nomogram was 0.751 (95% CI, OR: 0.708-0.793). The calibration curves in the validation and training sets showed good performance, indicating that the constructed nomogram model has good predictive ability. Additionally, the DCA demonstrated that the nomogram model has diagnostic accuracy. Conclusion: The Nomogram Model offers precise prognostications regarding the likelihood of Colorectal Cancer in patients, thereby helping healthcare professionals in their decision-making processes and promoting the rational categorization of patients as well as the allocation of medical resources.

Prognosis and immunotherapy response prediction based on M2 macrophage-related genes in colon cancer.

BACKGROUND: M2 macrophage were revealed to play a crucial role in immune evasion and immunotherapies. This study aims to explore the potential significance of M2 macrophage-related genes in colon adenocarcinoma (COAD) by analysizing the transcriptome data in a comprehensive way. METHODS: We collected RNA-sequencing (RNA-seq) data of COAD from The Cancer Genome Atlas (TCGA) and Gene Expression Ominibus (GEO) databases. We calculated the immune infiltration scores of every sample using CIBERSORT algorithm. Through weighted gene co-expression network analysis (WGCNA), we picked out M2 macrophage-related genes. With these genes we screened out prognosis related genes which were utilized to construct a signature to assess the prognosis of patients. To extend the potential application of the signature, we also calculated the correlations with immune infiltration. Finally, we applied techniques such as quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblotting (Western Blotting) to validate the RNF32 gene in cellular in vitro assays. RESULTS: Seven M2 macrophage-related genes signature was constructed, which was an excellent prognostic predictor in two independent groups. The high-risk group showed lower immune infiltration and poorer response to immunotherapies than those of the low-risk group. The cell vitro experiments showed that the expression level of RNF32 was upregulated in colon cancer cell lines compared with normal cell lines. Moreover, we found that RNF32 may promote the proliferation, migration and invasion of cancer cells in vitro by inhibiting apoptosis. CONCLUSION: A novel M2 macrophage-related gene signature affects the prognosis and immune characteristics of colon cancer.

Laparoscopic cholecystectomy for giant gallbladder: A case report.

RATIONALE: An overdistended gallbladder is usually observed in cases of distal bile obstruction due to malignancy. The gallbladder may also become enlarged and distended during cystic duct or gallbladder neck obstruction due to gallstones. However, a grossly distended gallbladder ( > 14 cm in length) without any pathology is rare. We present the case of a 46-year-old female patient who suffered from acute right lower quadrant pain for 4 days. Initially, a liver cyst and a choledochal cyst were diagnosed by the local hospital. Then, the diagnosis of giant gallbladder (measuring approximately 20.0 cm × 7.0 cm and containing more than 30 gallbladder stones) was made by magnetic resonance cholangiopancreatography at our hospital. Finally, we successfully performed a laparoscopic cholecystectomy and the patient had an uneventful recovery. PATIENT CONCERNS: A 46-year-old female patient presented with acute right lower quadrant pain lasting 4 days. At first, the abdominal pain was severe and paroxysmal, and then it subsided spontaneously. Computed tomography of the abdomen at another hospital revealed a hepatic cyst and a choledochal cyst. Come to our hospital for surgical treatment. DIAGNOSES: giant gallbladder with gallstones. INTERVENTIONS: Laparoscopic cholecystectomy was successfully performed in this patient after decompressing the gallbladder. OUTCOMES: On the third postoperative day, the patient recovered well, and the abdominal pain resolved following the operation. At the 3-year postoperative follow-up, the patient was symptom-free, with no obvious abnormalities seen in liver function and hepatobiliary color Doppler ultrasound. LESSONS: The patient was successfully treated using laparoscopic cholecystectomy. This rare case may contribute to the development of mechanisms for treating giant gallbladders.

Voltage-dependent modulation of TRPA1 currents by diphenhydramine.

Diphenhydramine (DPH) has been broadly used to treat allergy. When used as a topical medicine, DPH temporarily relieves itching and pain. Although transient receptor potential type A1 (TRPA1) channel is known to play roles in both acute and chronic itch and pain, whether DPH affects the activities of TRPA1 remains unclear. Using whole-cell patch clamp recordings, we demonstrated that DPH modulates the voltage-dependence of TRPA1. When co-applied with a TRPA1 agonist, DPH significantly enhanced the inward currents while suppressing the outward currents of TRPA1, converting the channel from outwardly rectifying to inwardly rectifying. This effect of DPH occurred no matter TRPA1 was activated by an electrophilic or non-electrophilic agonist and for both mouse and human TRPA1. The modulation of TRPA1 by DPH was maintained in the L906C mutant, which by itself also causes inward rectification of TRPA1, indicating that additional acting sites are present for the modulation of TRPA1 currents by DPH. Our recordings also revealed that DPH partially blocked capsaicin evoked TRPV1 currents. These data suggest that DPH may exert its therapeutic effects on itch and pain, through modulation of TRPA1 in a voltage-dependent fashion.

Mammalian STE20­like kinase 1 regulates pancreatic cancer cell survival and migration through Mfn2­mediated mitophagy.

Mammalian STE20-like kinase 1 (MST1) plays an important role in pancreatic cancer progression, but its downstream targets are still unknown. In the present study, our results indicated that MST1 expression was significantly downregulated in pancreatic cancer cell lines (PANC­1, BxPC­3 and HPAC) compared with that in the normal ductal epithelial cell line (hTERT­HPNE). Moreover, MST1 overexpression in PANC­1 cells led to increased apoptosis as determined by MTT and TUNEL assays and inhibited cellular migration. Mechanistically, upregulation of MST1 expression caused mitochondrial dysfunction, decreased ATP production, and activation of the mitochondrial­dependent apoptotic pathway via inhibition of mitofusin 2 (Mfn2)­mediated mitophagy, which ultimately resulted in increased cellular apoptosis and decreased cellular migration. Collectively, the present study demonstrated that MST1 may regulate pancreatic cancer PANC­1 cell survival, invasion and migration through Mfn2­mediated mitophagy, laying the foundation for the exploration of novel therapeutic targets for pancreatic cancer.

RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-κB pathways.

This study aimed to investigate the function and the molecular mechanism of Ribophorin II (RPN2) in regulating Hepatocellular carcinoma (HCC) cell growth, metastasis, and autophagy. Quantitative real-time PCR (qPCR), western blotting analysis, and immunofluorescence assay were utilized to detect the RPN2 expression in HCC cell lines and specimens of HCC patients. We discovered that RPN2 expression was upregulated in HCC cell lines and tissues of HCC patients, which correlated with the low histological grade and low survival rate. Enhanced RPN2 expression stimulated cell proliferation, metastasis, invasion, and epithelial-mesenchymal transition (EMT), and decreased Microtubule-associated protein light chain 3B (LC3B) synthesis and reduced the expression of p62 protein. Further studies suggested that matrix metalloproteinase 9 (MMP-9) was partially upregulated by RPN2 via Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65. Interestingly, we found that phosphorylated RPN2 activated the signal transducer and activator of transcription 3 (STAT3) in HCC cells. It was also accountable for RPN2-stimulated elevated expression of MMP-9 and for invading HCC cells. It can be concluded that over-expression of RPN2 in HCC aggravated the malignant progression into cancerous cells. This research provided new evidences that RPN2 could facilitate tumor invasion by increasing the expression of MMP-9 in HCC cells.

Laminarin enhances the activity of natural killer cells in immunosuppressed mice.

The aim of the study was to investigate the effects of laminarin on natural killer (NK) cell cytotoxicity of immunosuppressive mice and its mechanism. Cyclophosphamide (cy) was used to make an immunosuppressive model of mice. The mice of two groups were given interventions by gavage with laminarin 500 mg/kg and 1000 mg/kg every day for 10 days. MACS was adopted to isolate spleen NK cells, and cytotoxicity of NK cells and IL-12, IFN-γ level in serum were detected in vivo. Cytotoxicity of NK92-MI cells, activating receptors (NKp30, NKp44, NKp46 and NKG2D) and perforin and granzyme B expression were detected in vitro. Compared to the normal control group, the cytotoxicity of NK cells, IL-12 and IFN-γ level in serum in the cy model group were all reduced significantly (p < 0.01). Compared to the cy model group, laminarin increased the cytotoxicity of NK cells, IL-12 and IFN-γ levels in serum significantly (p < 0.05). In vitro, laminarin increased the cytotoxicity, NKp30 and NKG2D, perforin and granzyme B expressions of NK92-MI cells (p < 0.01). This research showed that laminarin can promote NK cell cytotoxicity in immunosuppressive mice by increasing the levels of IL-12 and IFN-γ in serum and expressions of NKp30 and NKG2D, perforin and granzyme B.

Long Non-coding RNA LINC00114 Facilitates Colorectal Cancer Development Through EZH2/DNMT1-Induced miR-133b Suppression.

This study aimed to identify the roles of the long non-coding RNA LINC00114 in colorectal cancer (CRC) development. The expression levels of LINC00114 and miR-133b in CRC were determined by reverse transcription (RT)-polymerase chain reaction (PCR) and the functions of LINC00114 in CRC were evaluated in vitro and in vivo. Methylation-specific PCR assay was performed to detect the miR-133b promoter methylation in CRC cells. Bioinformatics analysis, RNA immunoprecipitation, dual luciferase assay, RNA pull-down, co-immunoprecipitation (IP), and chromatin IP (ChIP) assays were used to elucidate whether LINC00114 could recruit EZH2/DNMT1 and bind to the miR-133b promoter region, leading to dysregulated methylation and the depression of miR-133b. The expression levels of DNA methyltransferases (DNMTs), EZH2, and nucleoporin 214(NUP214) were analyzed by western blotting. Data showed that LINC00114 was highly expressed, whereas miR-133b was downregulated in the CRC tissues and cells. In vitro, silencing LINC00114 inhibited cell proliferation and impeded cell cycle at the G1/S phase by upregulating miR-133b. In vivo, LINC00114 knockdown reduced tumor growth. Further analysis showed that the methylation in miR-133b promoter region was increased in the CRC and silencing LINC00114 increased miR-133b expression through depressing methylation of its promoter region. ChIP-PCR experiments demonstrated that EZH2 and DNMT1 could bind to the miR-133b promoter region and it was abolished by LINC00114 knockdown. sh-EZH2 reversed the overexpression of DNMTs and CRC cell cycle progression induced by the LINC00114 upregulation. LINC00114 could regulate the NUP214 protein expression by sponging miR-133b. These results demonstrated that LINC00114 suppressed miR-133b expression via EZH2/DNMT1-mediated methylation of its promoter region, indicating that LINC00114 might be a potential novel target for CRC diagnosis and treatment.

Transumbilical single-incision laparoscopic-assisted technique for removal of ileocecal foreign body.

The aim of this paper is to present the case of a 40-year-old man who accidentally ingested a piece of metal. The patient complained of having intermittent right lower quadrant abdominal pain for 2 days. An abdominal X-ray was performed, and a piece of metal was found in the right lower quadrant of the abdomen. There was no gas in the abdominal cavity. Surgical treatment was therefore needed. Single-incision laparoscopic surgery (SILS) was attempted with conventional laparoscopic instruments. The foreign body was identified around the ileocecal region, an enterostomy was made and the foreign body was successfully removed. Subsequently, the incised ileocecal was wall sutured. The time for this surgery was 1 h with little bleeding. The patient made a quick recovery with a good cosmetic outcome. Based on this case, the use of SILS-assisted technique in the removal of an ileocecal foreign body proves to be safe and feasible.

Combination therapy versus pharmacotherapy, endoscopic variceal ligation, or the transjugular intrahepatic portosystemic shunt alone in the secondary prevention of esophageal variceal bleeding: a meta-analysis of randomized controlled trials.

Patients with liver cirrhosis and variceal hemorrhage are at increased risk of rebleeding. We performed a meta-analysis toassess the clinical efficacy of combination therapy (pharmacotherapy and endoscopic variceal ligation (EVL)) compared with pharmacotherapy, EVL, or transjugular intrahepatic portosystemic shunt (TIPS) alone in the prevention of rebleeding and mortality. A literature search of MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, up until November 2016, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0. Regarding overall mortality, combination therapy was as effective as EVL, pharmacotherapy, and TIPS (relative risk (RR) = 0.62, 95% confidence interval (CI): 0.36-1.08, RR=1.05, 95% CI: 0.68-1.63, and RR=1.39, 95% CI: 0.92-2.09, respectively). Combination therapy was as effective as EVL and pharmacotherapy alone in reducing blood-related mortality (RR=0.43, 95% CI: 0.15-1.25, and RR=0.42, 95% CI: 0.17-1.06), whereas TIPS was more effective than combination therapy (RR=5.66, 95% CI: 1.02-31.40). This was also the case for rebleeding; combination therapy was more effective than EVL and pharmacotherapy alone (RR=0.57, 95% CI: 0.41-0.79, and RR=0.65, 95% CI: 0.48-0.88), whereas TIPS was more effective than combination therapy (RR=9.42, 95% CI: 2.99-29.65). Finally, regarding rebleeding from esophageal varices, combination therapy was as effective as EVL alone (RR=0.59, 95% CI: 0.33-1.06) and was more effective than pharmacotherapy alone (RR=0.58, 95% CI: 0.40-0.85), although was less effective than TIPS (RR=2.20, 95% CI: 1.22-3.99). TIPS was recommended as the first choice of therapy in the secondary prevention of esophageal variceal bleeding.

Regulatory role of miR-211-5p in hepatocellular carcinoma metastasis by targeting ZEB2.

Hepatocellular carcinoma (HCC) is the most common type of cancer and the rapid tumor growth, drug resistance and metastasis are the major problems for HCC therapy. MicroRNAs (miRNAs) involve in various cell biological processes in HCC. ZEB2 plays crucial roles in HCC progression. ZEB2 is regulated by some identified miRNAs, but there needs to find new miRNAs regulating ZEB2 expression for better understanding the molecular mechanism of HCC. In the present study, ZEB2 was identified as a direct target of miR-211-5p, which was a potential oncogene in cancer. We found that miR-211-5p levels in HCC tissues were lower than the compared normal tissues. ZEB2 expression was higher in HCC tissues and was negatively related to miR-211-5p levels. Overexpression of miR-211-5p in human HCC cell lines (HepG2 and 7721) caused the delay of cell proliferation, apoptosis and drug sensitivity. Summarily, our study demonstrates that miR-211-5p may play a suppressing role in HCC by inhibiting ZEB2 expression.

miR-204-5p targeting SIRT1 regulates hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is the most common type of cancer, which presents rapid tumor growth, drug resistance, and metastasis. Recently, microRNAs are shown to be involved in the cell biological processes in HCC, but the underlying molecular mechanisms remain unclear. This study aimed to investigate the cellular function and molecular mechanism of miR-204-5p in HCC. SIRT1 mRNA and miR-204-5p were examined by real-time reverse transcription polymerase chain reaction. SIRT1 protein levels were measured by Western blotting. Cell proliferation assay was performed to confirm colony formation. Invasion assay was performed by transwell system. SPSS 15.0 for Windows was used for statistical analysis. SIRT1 was a potential oncogene in cancer, which was identified as a direct target of miR-204-5p. Overexpression of miR-204-5p in human HCC cell lines (BEL-7405 and QGY-7701) caused the suppression of cell survival ability, the increase of apoptosis, and drug sensitivity. SIRT1 was overexpressed in human HCC tissues and was negatively related to miR-204-5p levels. These results indicate that miR-204-5p and SIRT1 may play an important role in the development of HCC.

Promoter Methylation of the Retinoic Acid Receptor Beta2 (RARß2) Is Associated with Increased Risk of Breast Cancer: A PRISMA Compliant Meta-Analysis.

BACKGROUND: Epigenetic studies demonstrate that an association may exist between methylation of the retinoic acid receptor beta2 (RARß2) gene promoter and breast cancer onset risk, tumor stage, and histological grade, however the results of these studies are not consistent. Hence, we performed this meta-analysis to ascertain a more comprehensive and accurate association. MATERIALS AND METHODS: Relevant studies were retrieved from the PubMed, Embase and Chinese National Knowledge Infrastructure databases up to February 28, 2015. After two independent reviewers screened the studies and extracted the necessary data, meta-analysis was performed using Review Manager 5.2 software. RESULTS: Nineteen eligible articles, including 20 studies, were included in our analysis. Compared to non-cancerous controls, the frequency of RARß2 methylation was 7.27 times higher in patients with breast cancer (odds ratio (OR) = 7.27, 95% confidence interval (CI) = 3.01-17.52). Compared to late-stage RARß2 methylated patients, the pooled OR of early-stage ones was 0.81 (OR = 0.81, 95% CI = 0.55-1.17). The OR of low-grade RARß2 methylated patients was 0.96 (OR = 0.96, 95% CI = 0.74-1.25) compared to high-grade RARß2 methylated patients. CONCLUSION: RARß2 methylation is significantly increased in breast cancer samples when compared to non-cancerous controls. RARß2 could serve as a potential epigenetic marker for breast cancer detection and management.

Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid) electrospun fibrous scaffold for bone regeneration.

A mesoporous bioactive glass (MBG) surface modified with poly(lactic-co-glycolic acid) (PLGA) electrospun fibrous scaffold for bone regeneration was prepared by dip-coating a PLGA electrospun fibrous scaffold into MBG precursor solution. Different surface structures and properties were acquired by different coating times. Surface morphology, chemical composition, microstructure, pore size distribution, and hydrophilicity of the PLGA-MBG scaffold were characterized. Results of scanning electron microscopy indicated that MBG surface coating made the scaffold rougher with the increase of MBG content. Scaffolds after MBG modification possessed mesoporous architecture on the surface. The measurements of the water contact angles suggested that the incorporation of MBG into the PLGA scaffold improved the surface hydrophilicity. An energy dispersive spectrometer evidenced that calcium-deficient carbonated hydroxyapatite formed on the PLGA-MBG scaffolds after a 7-day immersion in simulated body fluid. In vitro studies showed that the incorporation of MBG favored cell proliferation and osteogenic differentiation of human mesenchymal stem cells on the PLGA scaffolds. Moreover, the MBG surface-modified PLGA (PLGA-MBG) scaffolds were shown to be capable of providing the improved adsorption/release behaviors of bone morphogenetic protein-2 (BMP-2). It is very significant that PLGA-MBG scaffolds could be effective for BMP-2 delivery and bone regeneration.

Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma.

The association between hepatocellular carcinoma (HCC) and the epidermal growth factor (EGF) 61A/G polymorphism has been analyzed in several studies, but results remain inconsistent. Therefore, the aim of the present study was to quantitatively summarize the association between the EGF 61A/G polymorphism and the risk of HCC. The PubMed and EMBASE databases were searched for studies published prior to May 1, 2014. The overall, subgroup and sensitivity analyses were conducted using Comprehensive Meta-Analysis software, version 2.2. In total, 12 published case-control studies, consisting of 2,095 patients with HCC and 3,766 control individuals, were included in the present study. Meta-analysis of the included studies revealed that EGF 61A/G polymorphism contributed to the risk of HCC under all four genetic models, consisting of the G vs. A (OR, 1.25; 95% CI, 1.11-1.40), GG vs. AA (OR, 1.53; 95% CI, 1.26-1.85), GG vs. AG + AA (OR, 1.34; 95% CI, 1.13-1.58) and GG + AG vs. AA (OR, 1.27; 95% CI, 1.08-1.49) comparisons. Subgroup analysis further suggested that EGF 61A/G polymorphism was associated with the risk of HCC in patients and control individuals with liver disease, based on ethnicity and source of control, respectively. No other significance in residual subgroup analysis was observed. The present meta-analysis suggests that the EGF 61A/G polymorphism is associated with an increased risk of HCC and may be a potential marker for liver disease, such as hepatitis B virus infection, hepatitis C virus infection and liver cirrhosis.

XIAP is related to the chemoresistance and inhibited its expression by RNA interference sensitize pancreatic carcinoma cells to chemotherapeutics.

OBJECTIVES: To explore the exact role does the x-linked inhibitor of apoptosis (XIAP) play in chemoresistance of pancreatic carcinoma cell and the cell sensitivity to chemotherapeutic drugs changed after XIAP is inhibited by RNA interference (RNAi). METHODS: Pancreatic carcinoma cell line SW1990 was exposed to 5-fluorouracil (5-fu) with the concentrations of 1.0 and 10 mug/mL to increase the expression of XIAP. Then 4 RNAi plasmid vectors against XIAP were designed and constructed, then transfected into SW1990. Repressive effect was evaluated by reverse transcriptase polymerase chain reaction and Western blot; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry were performed to determine cell sensitivity to 5-fu and gemcitabine; furthermore, apoptosis is confirmed by Hoechst 33258 stain. RESULTS: XIAP of SW1990 can be up-regulated with the chemoresistance increasing 1.5- and 4-fold after 10 and 30 days induced by 5-fu. Two of the 4 vectors can inhibit the expression of XIAP protein more than 60%. The cells apoptosis index induced by 5-fu and gemcitabine increased greatly after XIAP is inhibited by the RNAi plasmid vectors. CONCLUSIONS: XIAP is one of the most important factors in the pancreatic carcinoma chemoresistance, and inhibition of XIAP in pancreatic carcinoma can enhance the cancer sensitivity to chemotherapeutic drugs.