Disulfidptosis and ferroptosis related genes predict prognosis and personalize treatment for hepatocellular carcinoma.

Background: Understanding the interplay between disulfidptosis, ferroptosis, and hepatocellular carcinoma (HCC) could provide valuable insights into the pathogenesis of HCC and potentially identify novel therapeutic targets for the treatment of this deadly disease. This study aimed to identify a prognostic signature for HCC by examining the differential expression of genes related to disulfidptosis and ferroptosis (DRG-FRG), and to assess its clinical applicability. Methods: By integrating 23 disulfidptosis and 259 ferroptosis related genes with HCC messenger RNA (mRNA) expression data from The Cancer Genome Atlas (TCGA), differentially expressed DRG-FRG genes were identified. From these, 11 DRG-FRG genes were selected to construct a risk signature model using least absolute shrinkage and selection operator regression analyses. The prognostic performance of this model was evaluated by Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) analysis. Subsequently, a nomogram was built by combining the signature with clinical variables. To further delve into the underlying mechanisms, we performed bioinformatics analysis using a variety of databases. Results: A prognostic signature based on 11 DRG-FRG genes effectively categorized HCC patients into high- and low-risk groups, showing a significant survival difference. Even after considering clinical variables, this signature remained an independent prognostic factor. Furthermore, the signature played a role in various critical biological processes and pathways that drive HCC progression. Potential therapeutic benefits could be derived from small molecule drugs targeting NQO1 and SLC7A11. Interestingly, the high-risk group exhibited resistance to several chemotherapeutic drugs, yet showed sensitivity to others when contrasted with the low-risk group. Lastly, the DRG-FRG genes signature had a strong correlation with the tumor immune microenvironment, marked by an elevated expression of immune checkpoint molecules in the high-risk group. Conclusions: The signature based on 11 DRG-FRG genes stands out as a promising prognostic biomarker for HCC. Beyond its predictive value, it sheds light on the intricate crosstalk between DRG-FRG genes and HCC. Importantly, these findings could pave the way for enhanced prognostic prediction, informed treatment decisions, and the advancement of immunotherapy for HCC patients.

ß -Glucan Improves Protective Qi Status in Adults with Protective Qi Deficiency-A Randomized, Placebo-Controlled, and Double-Blinded Trial.

OBJECTIVE: To test the hypothesis that ß -glucan enhances protective qi (PQi), an important Chinese medicine (CM) concept which stipulates that a protective force circulates throughout the body surface and works as the first line of defense against "external pernicious influences". METHODS: A total of 138 participants with PQi deficiency (PQD) were randomized to receive ß -glucan (200 mg daily) or placebo for 12 weeks. Participants' PQi status was assessed every 2 weeks via conventional diagnosis and a standardized protocol from which a PQD severity and risk score was derived. Indices of participants' immune and general health status were also monitored, including upper respiratory tract infection (URTI), saliva secretory IgA (sIgA), and self-reported measures of physical and mental health (PROMIS). RESULTS: PQi status was not significantly different between the ß -glucan and placebo treatment groups at baseline but improved significantly in the ß -glucan (vs. placebo) group in a time-dependent manner. The intergroup differences [95% confidence interval (CI)] in severity score (scale: 1-5), risk score (scale: 0-1), and proportion of PQD participants (%) at finish line was 0.49 (0.35-0.62), 0.48 (0.35-0.61), and 0.36 (0.25-0.47), respectively. Additionally, ß -glucan improved URTI symptom (scale: 1-9) and PROMIS physical (scale: 16.2-67.7) and mental (scale: 21.2-67.6) scores by a magnitude (95% CI) of 1.0 (0.21-1.86), 5.7 (2.33-9.07), and 3.0 (20.37-6.37), respectively, over placebo. CONCLUSIONS: ß -glucan ameliorates PQi in PQD individuals. By using stringent evidence-based methodologies, our study demonstrated that Western medicine-derived remedies, such as ß -glucan, can be employed to advance CM therapeutics. (ClinicalTrial.Gov registry: NCT03782974).

Proof-of-Concept and Feasibility Study to Evaluate the Effect of ß-Glucan on Protective Qi Deficiency in Adults.

OBJECTIVE: To preliminarily explore the potential effect of ß-glucan on Chinese medicine (CM) concept protective qi deficiency (PQD), and the methodology for future definitive studies. METHODS: To have a standardized assessment of PQD, a list of 13 potentially PQD-relevant parameters were firstly created, each with defined quantitative or categorial scales. Using the data from 37 participants with (21 cases) or without (16 cases) PQD, multivariate logistic modeling was conducted to create a preliminary diagnostic PQD risk score. Subsequently, 21 participants diagnosed with PQD were treated with ß-glucan in a dose of 200 mg/day for 8 weeks. Data were collected for trial acceptability measures (rate of recruitment, withdrawal, and compliance), and the participants were assessed for PQD status at baseline and every 2 weeks thereafter. RESULTS: The preliminary logistic model consisted of 3 parameters (low voice and apathy, aversion to wind and cold, and Cun pulse). The resulting risk score demonstrated a degree of PQD-predicting accuracy that, as evaluated by statistical (discrimination and classification) methods, was higher than those obtained from any of the individual candidate parameters. The 21 PQD participants treated with ß-glucan demonstrated good receptibility and a time-dependent improvement in PQD status as evidenced by the decrease of PQD participant to 9.5% at the end of study. CONCLUSIONS: This study demonstrated the effect of proof-of-concept of ß-glucan on improving PQD and the proof-of-concept of a multivariate-model-derived diagnostic PQD risk score. It also indicated feasibility for future definitive studies. Studies like this embody an innovative approach that uses therapies derived from the mainstream biomedicine to enrich therapeutics guided by CM principle. (Trial registration No. NCT03829228).

Effect of lncRNA­BC200 on proliferation and migration of liver cancer cells in vitro and in vivo.

In recent years, the important role of long non­â€‹coding RNAs (lncRNAs) in the development of liver cancer has received increasing attention. The abnormal expression level of long non­coding RNAs has been associated with the occurrence and development of liver cancer. However, the role and molecular mechanisms of lncRNAs in the development and progression of liver cancer are not fully understood. The present study aimed to clarify the function and molecular mechanism of lncRNA brain cytoplasmic 200 (BC200) in liver cancer. In the present study, it was found that BC200 expression level was higher in hepatocellular carcinoma (HCC) tissues than that in adjacent tissues. Cell function was examined by constructing BC200 knockout (KO) and BC200­overexpression in vitro models. It was found that BC200 affected the proliferation and migration of HepG2 cells. Interestingly, it was found that BC200 affected the expression of c­Myc protein but did not affect the mRNA expression level of c­MYC. BC200 KO cells exhibited a reduced protein expression level of Bax protein and an increased protein expression level of Bcl­xL. Conversely, BC200 overexpression reduced the expression of Bcl­xL protein and increased the expression of Bax protein. Importantly, it was found that BC200 affected the formation of subcutaneous tumors in nude mice. In conclusion, the present results suggested that lncRNA BC200 may play an important role in liver cancer.

Estrogen receptor 1 and progesterone receptor are distinct biomarkers and prognostic factors in estrogen receptor-positive breast cancer: Evidence from a bioinformatic analysis.

PURPOSE: Few prognostic indicators involving differentially expressed genes (DEGs) between estrogen receptor (ER)-positive and ER-negative breast cancer (BC) have been reported. We aimed to screen important DEGs related to ER status and explore potential prognostic factors for patients with ER-positive BC. MATERIALS AND METHODS: Two microarray datasets (GSE22093 and GSE23988) downloaded from the Gene Expression Omnibus database were analyzed to identify DEGs between ER-positive and ER-negative BC tissue. Functional enrichment analysis of DEGs was performed using the Database for Annotation, Visualization, and Integrated Discovery server. Protein-protein interactions of the DEGs were analyzed using the Search Tool for the Retrieval of Interacting Genes. Subsequently, we studied the expression of hub genes in different histological types of BC using the Oncomine database. The online Kaplan-Meier (K-M) plotter survival analysis tool was utilized to evaluate the prognostic value of the expression of hub genes in ER-positive BC patients. Based on the results of K-M plotter analysis, we investigated the expression profiles of significant hub genes in an array of cancer cell lines using the Cancer Cell Line Encyclopedia database. RESULTS: A total of 194 DEGs were identified, comprising 141 upregulated and 53 downregulated genes. GO analysis revealed that the DEGs were mainly enriched in the extracellular exosome of the cellular component category. Ten hub genes were upregulated in ER-positive BC, and overexpression of estrogen receptor 1 (ESR1) mRNA was correlated with worse relapse-free survival (RFS). In contrast, overexpressed mRNA of progesterone receptor (PGR) was associated with longer RFS in patients with ER-positive BC. The expression of ESR1 was associated with GATA3, whereas that of PGR was correlated with ABLIM3. Both ESR1 and PGR were highly expressed in BC cell lines. CONCLUSIONS: The results suggest that mRNA expression levels of ESR1 and PGR can be considered distinct biomarkers and essential prognostic factors for ER-positive BC.

Osimertinib or EGFR-TKIs/chemotherapy in patients with EGFR-mutated advanced nonsmall cell lung cancer: A meta-analysis.

BACKGROUND: The aim of this meta-analysis is to investigate the impact of Osimertinib on treatment efficacy in advanced nonsmall cell lung cancer (NSCLC). METHODS: Trials comparing Osimertinib against epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)/chemotherapy in patients with NSCLC with an epidermal growth factor receptor (EGFR) mutation were included, and the pooled data for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. RESULTS: Analysis results based on 6 eligible trials showed that Osimertinib significantly improved the overall PFS (hazard ratio [HR] = 0.38, 95% confidence interval [CI] = 0.29-0.50), improved the OS (HR = 0.66, 95% CI = 0.48-0.89), increased the ORR (odds ratio [OR] = 1.76, 95% CI = 1.14-2.72), increased the overall DCR (OR = 1.18, 95% CI = 1.02-1.37), and reduced the grade 3 or greater AEs (relative ratio [RR] = 0.50, 95% CI = 0.33-0.75) in all subgroups except in the ORR in the Exon 19 deletion (Ex19del) and/or L858R subgroup. Compared to patients with Ex19del and/or L858R mutation, patients with the T790M mutation had the benefits of a greater PFS (41.7%), a greater ORR (80.0%), a greater DCR (71.2%), and fewer grade 3 or greater AEs (70.7%) (each P < .05). Race, sex, age, EGFR mutation, and smoking history may significantly predict additional benefits from Osimertinib, but there were no significant differences between subgroups stratified by these clinical characteristics. CONCLUSIONS: Osimertinib showed greater treatment benefit for patients with NSCLC with EGFR mutation than EGFR-TKIs/chemotherapy, especially for T790M mutation-positive patients.

High standardized uptake values of 18F-FDG PET/CT imaging but not MRI correlates to pathology findings in patients with cervical cancer.

OBJECTIVE: This study was to explore the correlation between the standardized uptake value (SUV) of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging and the apparent diffusion coefficient (ADC) value of magnetic resonance imaging (MRI) to the pathological features of cervical cancer (CC). SUBJECTS AND METHODS: The maximum and mean SUV of 18F-FDG PET/CT (SUVmax and SUVmean) and the minimum ADC (ADCmin) were collected from 72 patients with CC. The correlation between SUVmax and ADCmin was also assessed. Furthermore, the relationship between SUVmax, SUVmin, ADCmin and the clinical pathological characteristics of CC was analyzed. RESULTS: A significant increase in the SUVmax was observed in the group of CC cases with lymph node metastases and in the group with distant metastases compared to those without metastases (F=6.782, P=0.002; F=4.483, P=0.015). Furthermore, in the low differentiation groups compared to high/middle differentiation groups (F=3.342,P=0.024), in the squamocellular carcinoma groups compared to the adenocarcinoma and adenosquamous carcinoma groups (F=3.295, P=0.026) and finally in the International Federation of Gynecology and Obstetrics (FIGO) stage III-IV groups compared with stage III-IV groups (F=3.123, P=0.020).The SUVmean values of the lymph node metastases and distant metastases groups were significantly higher than those without lymph node metastases (F=5.802, P=0.005; F=3.486, P=0.036). We saw no correlation between the ADCmin and lymph node metastases. The SUVmax value had weak correlation with the ADCmin (r=-0.306, P=0.036). The SUVmax is most closely related to the clinical pathological characteristics of CC. CONCLUSION: An increased SUVmax suggests lymph node metastases or distant metastases, low differentiation and FIGO stage III-IV. A low negative correlation was observed between the SUVmax and ADCmin, while we observed no correlation between the ADCmin and the clinical pathological characteristics of cervical cancer.

The role of ERCC1 and AFP gene polymorphism in hepatocellular carcinoma.

The aim of this study was to evaluate the effects of polymorphisms in excision repair cross-complementation group 1 (ERCC1) and alpha-fetoprotein (AFP) genes and their haplotypes on the susceptibility to hepatocellular carcinoma (HCC), and to decipher the association between single-nucleotide polymorphisms (SNPs) and clinicopathologic characteristics of HCC.Peripheral blood DNA was extracted from 206 subjects. SNaPshot technique was used for genotyping 5 SNP sites of the ERCC1 rs735482, rs1046282, rs3212948, and AFP rs737241, rs4024 genotypes. Chi-squared test and logistic regression model were used to analyze the relationship of different genotypes or haplotype and the susceptibility and clinicopathologic characteristics of HCC.The frequency of GG.GA and AA genotypes at the AFP rs737241 site in the case and control groups showed statistically significant differences (P < .05). The risk of HCC in subjects carrying mutated allele A (GA+AA) was increased by 0.543-times (P < .05) compared to that in the subjects with the GG genotype. Significant differences were observed in the linkage disequilibrium between 2 of the five SNPs (P < .05); the frequency of ERCC1 C-C and AFP A-A haplotypes was significantly lower in the case group than in the control group (P < .05). The results of clinicopathologic analysis showed that A allele at the rs737241 locus could increase the expression level of AFP (P = .007), the rs1046282 mutation C allele could increase the AFP expression level (P = .011), rs4024 locus mutation A allele could reduce the risk of vascular invasion (P = .013), rs3212948 locus mutation T allele could reduce the differentiation of liver cancer (P = .022), rs1046282 locus C allele could reduce the DNA load of hepatitis B virus (P = .035), and rs735482 A allele could increase the tumor size in HCC (P = .037).The SNPs in rs737241 for AFP gene may correlate with the occurrence of HCC. The SNPs in ERCC1 and AFP genes may affect the prognosis of HCC, offering reliable information for early prediction of tumor progression and diagnosis of HCC.

Burkholderia pseudomallei infection presenting with a lung abscess and osteomyelitis in an adult man: A case report.

RATIONALE: The frequency of infections caused by Burkholderia pseudomallei is increasing worldwide. Here, we report a case of B pseudomallei infection presenting with a lung abscess and osteomyelitis in an adult man. PATIENT CONCERNS: A 38-year-old man presented with high-grade fever, productive cough, and chronic joint pain of the limbs. Examinations revealed multiple nodules, soft tissue mass shadows, pulmonary cavitation in bilateral lungs, and fluid and soft tissue swelling in bilateral hips. DIAGNOSES: The microbiologic diagnosis based on a positive culture revealed the etiologic agent to be B pseudomallei. INTERVENTIONS: The patient was treated with intravenous ceftazidime and levofloxacin, and out-of-hospital treatment continued with oral cotrimoxazole. OUTCOMES: The patient responded well to the treatment. LESSONS: subsections Because of its increasing incidence, B pseudomallei infection should be highly suspected among employees who work in laboratories and healthcare facilities. Misdiagnosis can lead to treatment failure and high mortality rates, especially among individuals working in laboratories in non-endemic areas; therefore, early and accurate diagnosis of B pseudomallei infection is essential. Adequate antimicrobial treatment and long-term follow-up are imperative to reduce morbidity and mortality.

A Retrospective Comparison of Trastuzumab Plus Cisplatin and Trastuzumab Plus Capecitabine in Elderly HER2-Positive Advanced Gastric Cancer Patients.

A combination of trastuzumab and cisplatin or trastuzumab and capecitabine has been confirmed to be effective for treating adverse effects in with HER2-positive advanced gastric cancer (AGC) patients. We retrospectively compared the activity and safety of trastuzumab plus cisplatin (HP) and trastuzumab plus capecitabine (HX) for elderly HER2-positive AGC patients.Ninety two HER2-positive AGC patients were included in this study; of those 48 patients received trastuzumab (course 1, 8 mg/kg followed by course 2, onward, 6 mg/kg on day 1) plus cisplatin (60 mg/m) intravenously on day 1 of a 3-week cycle and 44 patients received trastuzumab (course 1, 8 mg/kg; course 2 onward, 6 mg/kg) plus intravenous oral capecitabine (1000 mg/m twice daily on days 1-14), every 3 weeks. The primary end point was overall survival (OS). The secondary end points included objective response rate (ORR), progression-free survival (PFS), and toxicity.The median age was 71 years in both groups. The median OS was 15.5 months in the HP group and 17.0 months in the HX group, with no significant difference between the 2 groups (P = 0.78). There were also no significant differences in PFS (median 6.6 months vs 7.2 months, respectively; P = 0.90) and ORR (58.3% vs 59.1%, respectively; P = 1.00) between the HP group and the HX group. The major grade 3 or 4 adverse events in the HP group and the HX group were neutropenia (35.4% vs 29.5%, respectively), followed by anorexia (25.0% vs 22.7%, respectively), and anemia (16.7% vs 13.6%, respectively), no significant differences were observed.HP and HX were associated with similar efficacy and safety in HER2-positive AGC patients.

S-1-based therapy versus S-1 monotherapy in advanced gastric cancer: a meta-analysis.

This study aimed to derive a more precise estimate of the prognostic significance of S-1-based therapy over S-1 monotherapy in patients with advanced gastric cancer (AGC), including overall survival (OS) time, progression-free survival (PFS) time, objective response rate (ORR), and adverse events (AEs). Studies stratifying OS, PFS, ORR, and AEs in AGC patients in an S-1-based therapy versus an S-1 monotherapy setting were eligible for analysis by systematic computerized PubMed, Embase and Cochrane Library searches. Data from these studies were pooled using STATA package version 11.0. Six studies that investigated outcomes in a total of 913 AGC cases, of which 443 (48.5%) received S-1-based therapy and 470 (51.5%) received S-1 monotherapy, were included in the meta-analysis. Median OS and median PFS were significantly prolonged in AGC patients receiving S-1-based therapy compared with those receiving S-1 monotherapy (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.71-0.96, P = 0.015, and HR 0.69, 95% CI 0.60-0.80, P = 0.000, respectively). The ORR favored patients with S-1-based therapy (OR 1.65, 95% CI 1.34-2.06, P = 0.000). Higher incidence of grade 3/4 neutropenia was found in patients with S-1-based therapy (P = 0.000). For the Asian population, S-1-based therapy significantly improved OS and PFS and enhanced ORR in comparison to S-1 monotherapy. The safety profile was poorer in patients with S-1-based therapy, but could be considerable between the S-1-based therapy and S-1 monotherapy group. Our conclusion needs to be confirmed via high-quality trials and the results need to be reproduced in other regions and populations.

Association of XRCC3 Thr241Met polymorphisms and gliomas risk: evidence from a meta-analysis.

The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Met polymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphism and gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of nine case-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found that XRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10, 95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC: OR=1.29, 95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was found in Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36- 2.36, P=0.00; TT vs. TC/CC: OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20). This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especially for Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scale and well-designed studies are needed to confirm our results.