Clinical analysis of patients with skin metastasis of cervical squamous cell carcinoma.

BACKGROUND: Cancers that metastasize to the skin are rare, especially cervical squamous cell carcinoma to the skin. Here, we have reported clinical analysis of patients with cervical squamous cell carcinoma metastasize to skin, to obtain a general understanding of this malignancy for clinicians. METHODS: A retrospective analysis of patients with skin metastasis from cervical squamous cell carcinoma was conducted, focusing on clinical manifestations, histopathology, diagnosis, treatment, and prognosis. RESULTS: The average age of onset for the six patients with skin metastasis from cervical squamous cell carcinoma was 55.17±17.08 years, with four cases presenting as solitary lesions and two cases as multiple lesions. Treatment strategies included local excision for isolated lesions, chemotherapy, radiotherapy, or targeted therapy based on the extent of skin involvement, and immunotherapy was proved to have promising results in our cases. Among the six patients, three have passed away with a diagnosis-to-death time of approximately 5-6 months, while three patients are alive, with survival times ranging from 30 to 72 months. CONCLUSIONS: Skin metastasis from cervical squamous cell carcinoma is rare and often accompanies recurrent metastases to other visceral sites, necessitating early and accurate diagnosis. For isolated metastatic lesions, early detection followed by wide excision surgery and adjuvant radiotherapy can yield favorable outcomes. However, in cases of multiple skin metastases or concurrent metastases to multiple organs, treatment is challenging with a poor prognosis. Nevertheless, with advancements in medicine, combination chemotherapy, immunotherapy, and targeted therapy can effectively prolong survival, offering new hope for patients with skin metastasis from cervical cancer.

A comprehensive study of oxidative stress-related effects on the prognosis and drug therapy of cervical cancer.

BACKGROUND: Cervical cancer (CC) is a serious global disease with poor prognoses and a significant recurrence rate in patients with advanced disease. Oxidative stress (OS) greatly influences many types of human cancers, making it crucial to understand the functional mechanisms of OS-related genes in CC. METHODS: The transcriptome and clinical data of three normal samples and 306 patients with CC were obtained from The Cancer Genome Atlas dataset. The GSE44001 dataset was acquired from the Gene Expression Omnibus database. OS-related subtypes in the cohort with CC were identified using unsupervised hierarchical clustering, univariate Cox analysis, gene set enrichment analysis (GSEA), and least absolute shrinkage and selection operator regression analysis. Additionally, molecular pathways that differ across subtypes were determined and OS-related genes linked to the prognosis of patients of CC were determined. Finally, a clinical prognostic gene signature was developed and validated. The relative infiltration level of immune cell subpopulations in different risk groups and subtypes was evaluated using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERPORT) algorithm and single-sample GSEA (ssGSEA) techniques. RESULTS: The present study established two distinct OS subtypes (OS clusters A and B). Analysis using ssGSEA and CIBERSPORT revealed that OS cluster B exhibited a significant level of immune infiltration. A clinical prognostic gene signature was established using OS-related characteristic genes identified by examining the differentially expressed genes across both subtypes. Furthermore, patients with CC were grouped into high- and low-risk groups, with the low-risk group showing higher survival rates. Additionally, these individuals exhibited significant advantages in terms of survival and immunotherapy. Receiver operating characteristic curve analysis demonstrated the higher predictive value of the clinical prognostic gene signature. The outcomes of the validation group depicted congruence with those recorded in the training group. CONCLUSIONS: A new model was constructed based on eight OS-related characteristic genes to aid the prediction of the survival rates of individuals with CC. The present study contributes to the existing literature on the mechanisms of OS genes in CC and offers a fresh perspective for future advancements in immunotherapy for such individuals.

Derepressing of STAT3 and USP7 contributes to resistance of DLBCL to EZH2 inhibition.

Diffuse large B-cell lymphoma is the most common subtype of lymphoma, representing ∼25 % of non-Hodgkin lymphoid malignancies. EZH2 is highly expressed in Diffuse large B-cell lymphoma and ∼22 % of patients contain EZH2 mutations. EZH2 have been studied as a potential therapeutic target for a decade, but efficient inhibition of EZH2 did not robustly kill lymphoma cells. Here, we found that EZH2 mediates repression of oncogenic genes STAT3 and USP7 in Diffuse large B-cell lymphoma cells. Inhibition of EZH2 leads to upregulation of STAT3 and USP7 at both RNA and protein levels. Along with USP7 upregulation, MDM2 is upregulated and its ubiquitylation substrate, Tumor suppressor P53, is downregulated. Upregulation of STAT3 and downregulation of p53 can strength cell proliferation and prevent cells from apoptosis, which suggests resistance mechanisms by which cells survive EZH2 inhibition-induced cell death. Short-course co-inhibition of USP7 and EZH2 showed increased apoptosis and cell proliferation prevention with the concentration as low as 0.08 µM. In STAT3 and USP7 depleted cells, EZH2 inhibition shows superior efficacy of apoptosis, and in EZH2 depleted cells, USP7 inhibition also shows superior efficacy of apoptosis. Thus, our findings suggest a new precision therapy by combinational inhibition of EZH2 with STAT3 or USP7 for Diffuse large B-cell lymphoma.

Effect of bladder filling status on positioning errors in post-hysterectomy cervical cancer radiotherapy.

Objective: To investigate the effect of different bladder filling states on positioning errors in radiotherapy for cervical cancer and obtain the reference range of bladder filling consistency during radiotherapy.Methods: Patients who underwent postoperative radiotherapy for cervical cancer in Nantong Tumor Hospital from October 2018 to December 2019 were selected. According to the bladder filling deviation, they were divided into group A1 (deviation < 20%) and group B1 (deviation ≥ 20%). The bladder filling variations of the two groups were compared with different positioning errors. Group A2 has a positioning error of <0.4 cm, and group B2 has a positioning error of ≥0.4 cm. The reference range of bladder filling consistency during radiotherapy is obtained by analyzing the composition ratio of different positioning errors of bladder filling deviation.Results: This study included 195 patients with cervical cancer. The error of longitudinal and vertical position in group B1 was significantly higher than that in group A1 (0.50 ± 0.34 vs. 0.26 ± 0.22 cm, p < 0.001, and 0.22 ± 0.17 vs. 0.16 ± 0.12 cm, p < 0.001). Compared with group B2, the absolute deviation of bladder filling in group A2 (54.1% ± 54.4% vs. 25.6% ± 22.7%, p < 0.001) was slight. The chi-square test showed significant differences in the proportion of the positioning state of different bladder filling forms (χ2 = 31.006, p < 0.001). In addition, there was a significant difference in the proportion of stability errors in patients with poor stability in different directions (χ2 = 118.551, p < 0.001).Conclusion: In patients with cervical cancer fixed in the supine position, a bladder capacity deviation <20% is easier to achieve excellent positioning with, and it can better control the positioning error of radiotherapy and ensure the positioning accuracy of dose distribution to the target area. It can also achieve good tumor treatment effects. This range can be used as a reference for bladder filling consistency in patients with cervical cancer undergoing radiotherapy.

Association between chronic obstructive pulmonary disease and cardiovascular disease in adults aged 40 years and above: data from NHANES 2013-2018.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) are two major age-related diseases prevalent in the elderly. However, it is unclear whether there is a higher prevalence of one or more CVDs in COPD patients compared to those without COPD, and the magnitude of this increased prevalence. METHODS: This population-based cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2013-2018 among American adults aged 40 years and above. Multivariable logistic regression models (including unadjusted model, minimally adjusted model, and fully adjusted model) were conducted to investigate the association between COPD and the prevalence of one or more CVDs, including coronary heart disease, heart failure, angina pectoris, heart attack, diabetes, and stroke. RESULTS: This study included 11,425 participants, consisting of 661 participants with COPD and 10,764 participants without COPD. COPD patients had a significantly higher prevalence of CVD than those without COPD (59.6% vs. 28.4%). After adjusting for covariates, COPD was significantly associated with the prevalence of one CVD (OR = 2.2, 95% CI = 1.6-3.0, p < 0.001), two or more CVDs (OR = 3.3, 95% CI = 2.2-5.0, p < 0.001), and three or more CVDs (OR = 4.3, 95% CI = 2.9-6.5, p < 0.001). CONCLUSIONS: Patients with COPD have a higher prevalence of one or more CVDs compared with those without COPD. Our findings highlight the importance of CVD prevention and management in patients with COPD.

Detection and analysis of multiple biomarkers in ovarian cancer: clinical significance in diagnosis, treatment, and prognosis evaluation.

BACKGROUND: The purpose of this study was to explore the clinical significance of CA125, CK7, CK20, ER, PR, C-erbb2, and P-gp in ovarian cancer. METHODS: Ovarian cancer patients were recruited from Nantong Cancer Hospital between March 2006 and July 2011. The expressions of CA125, CK7, CK20, ER, PR, C-erbb2, and P-gp were determined by immunohistochemistry (IHC).The chi-square test (χ2) was used to analyze the correlation between each index and the clinical characteristics of the patients. The patients were followed up to record the cancer recurrence time. The Kaplan-Meier method was used to map the cumulative recurrence-free survival (RFS) rate, and COX regression analysis was established for multivariate analysis. RESULTS: The results of IHC showed that the positive expression rates of CA125, CK7, ER, C-erbb2, and P-gp in malignant ovarian cancer tissues were significantly higher than those in benign ovarian cancer tissues. CA125 expression in malignant ovarian cancer was significantly correlated with the age of patients and the Federation of International Gynecology and Obstetrics (FIGO) stage. CK7 expression in malignant ovarian cancer was significantly correlated with the age, tissue differentiation, and number of residual lesions. CK20 expression in malignant ovarian cancer was significantly correlated with the age and tissue differentiation of the patients. ER expression in malignant ovarian cancer was significantly correlated with the age of patients and FIGO stage. PR expression in malignant ovarian cancer was significantly correlated with the age of the patients. C-erbb2 expression in malignant ovarian cancer was significantly correlated with the age of the patients. P-gp expression in malignant ovarian cancer was significantly correlated with the patient age, pathological type, and tissue differentiation. The expression of CA125, CK7, CK20, C-erbb2, and P-gp had significant effects on the prognosis of patients with ovarian cancer. The COX regression analysis showed that P-gp was an independent risk factor for ovarian cancer. CONCLUSIONS: In malignant ovarian cancer tissues, CA125, CK7, CK20, ER, PR, C-erbb2, and P-gp are over-expressed. The expression of P-gp is an independent risk factor for ovarian cancer, and it can be an important target for the treatment of malignant ovarian cancer.

TLR4-MyD88-TRAF6-TAK1 Complex-Mediated NF-κB Activation Contribute to the Anti-Inflammatory Effect of V8 in LPS-Induced Human Cervical Cancer SiHa Cells.

The synthetic compound 7-4-[Bis-(2-hydroxyethyl)-amino]-butoxy-5-hydroxy-8-methoxy-2-phenylchromen-4-one (V8) is a novel flavonoid-derived compound. In this study, we investigated the effects of V8 on Toll-like receptor 4 (TLR4)-mediated inflammatory reaction in human cervical cancer SiHa cells and lipopolysaccharide (LPS)-induced TLR4 activity in cervical cancer SiHa (HPV16+) cells, but not in HeLa (HPV18+) and C33A (HPV-) cells. In addition, V8 inhibited LPS-induced expression of TLR4, MyD88, TRAF6 and phosphorylation of TAK1, and their interaction with TLR4 in SiHa cells, resulting in an inhibition of TLR4-MyD88-TRAF6-TAK1 complex. Moreover, V8 blocked LPS-induced phosphorylation of IκB and IKK, resulting in inhibition of the nuclear translocation of P65-NF-κB in SiHa cells. We also found that V8 reduced the expression of NF-κB target genes, such as those for COX-2, iNOS, IL-6, IL-8, CCL-2, and TNF-α in LPS-stimulated SiHa cells. These results suggested that V8 exerted an anti-inflammatory effect on SiHa cells by inhibiting the TLR4-MyD88-TRAF6-TAK1 complex-mediated NF-κB activation.

Can non-invasive positive pressure ventilation prevent endotracheal intubation in acute lung injury/acute respiratory distress syndrome? A meta-analysis.

The role of non-invasive positive pressure ventilation (NIPPV) in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is controversial. The aim of this study was to investigate whether NIPPV could prevent endotracheal intubation and decrease mortality rate in patients with ALI/ARDS. Randomized controlled trials (RCT) which reported endotracheal intubation and mortality rate in patients with ALI/ARDS treated by NIPPV were identified in Pubmed, Medline, Embase, Central Cochrane Controlled Trials Register, Chinese National Knowledge Infrastructure, reference lists and by manual searches. Fixed- and random-effects models were used to calculate pooled relative risks. This meta-analysis included six RCT involving 227 patients. The results showed that endotracheal intubation rate was lower in NIPPV (95% confidence interval (CI): 0.44-0.80, z = 3.44, P = 0.0006), but no significant difference was found either in intensive care unit (ICU) mortality (95% CI: 0.45-1.07, z = 1.65, P = 0.10) or in hospital mortality (95% CI: 0.17-1.58, z = 1.16, P = 0.25). Only two studies discussed the aetiology of ALI/ARDS as pulmonary or extra-pulmonary, and neither showed statistical heterogeneity (I(2) = 0%, χ(2) = 0.31, P = 0.58), nor a significant difference in endotracheal intubation rate (95% CI: 0.35-9.08, z = 0.69, P = 0.49). In conclusion, the early use of NIPPV can decrease the endotracheal intubation rate in patients with ALI/ARDS, but does not change the mortality of these patients.

Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a systematic review.

BACKGROUND: To evaluate the safety and efficacy of using sildenafil for ≥ 12 weeks to treat pulmonary arterial hypertension (PAH). METHODS: Randomized controlled trials (RCTs) of sildenafil therapy in patients with PAH published through May 2013 were identified by searching PubMed, the Cochrane Library, Embase, relevant websites, and reference lists of relevant studies. Two reviewers independently assessed the quality of the trials and extracted information. RESULTS: Meta-analysis was carried out with subsets of 4 trials involving 545 patients. Sildenafil therapy significantly reduced clinical worsening of PAH compared to placebo (RR 0.39, 95% CI 0.21-0.69) and improved the 6-min walk distance (MD 31.3 m, 95% CI 18.01-44.67), WHO functional class, hemodynamic variables and health-related quality of life (HRQoL). Sildenafil did not, however, improve all-cause mortality (RR 0.29, 95% CI 0.02-4.94) or Borg dyspnea score relative to placebo, nor did it significantly affect the incidence of serious adverse events. In fact, sildenafil was associated with higher total incidence of adverse events, but these additional events were mild to moderate in severity and were tolerable. CONCLUSIONS: Sildenafil therapy lasting ≥ 12 weeks improves multiple clinical and hemodynamic outcomes in patients with PAH, but it appears to have no effect on mortality or serious adverse events. The long-term efficacy and safety of sildenafil therapy in PAH requires further study based on large and well-designed RCTs.