WGCNA reveals a biomarker for cancer-associated fibroblasts to predict prognosis in cervical cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are crucial components of the cervical cancer tumor microenvironment, playing a significant role in cervical cancer progression, treatment resistance, and immune evasion, but whether the expression of CAF-related genes can predict clinical outcomes in cervical cancer is still unknown. In this study, we sought to analyze genes associated with CAFs through weighted gene co-expression network analysis (WGCNA) and to create a predictive model for CAFs in cervical cancer. METHODS: We acquired transcriptome sequencing data and clinical information on cervical cancer patients from the TCGA and GEO databases. Weighted gene co-expression network analysis was conducted to identify genes related to CAFs. We developed a prognostic model based on CAF genes in cervical cancer using LASSO Cox regression analysis. Single-cell sequencing data analysis and in vivo experiments for validation of hub genes in CAFs. RESULTS: A prognostic model for cervical cancer was developed based on CAF genes including COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1. Cervical cancer patients were divided into low and high risk groups based on the optimal cutoff value. Patients in the high risk group had significantly worse prognosis. Single-cell RNA sequencing data revealed that hub genes in the CAFs risk model were expressed mainly in fibroblasts. The real-time fluorescence quantitative PCR results revealed a significant difference in the expression levels of COL4A1, LAMC1, POSTN, and SERPINF1 between the cancer group and the normal group (p < 0.05). Consistently, the results of the immunohistochemical tests exhibited notable variations in COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1 expression between the cancer and normal groups (p < 0.001). CONCLUSION: The CAF risk model for cervical cancer constructed in this study can be used to predict prognosis, while the CAF hub genes can be utilized as crucial markers for cervical cancer prognosis.

M2-type tumor-associated macrophages upregulated PD-L1 expression in cervical cancer via the PI3K/AKT pathway.

BACKGROUND AND PURPOSE: PD-1/PD-L1 inhibitors have become a promising therapy. However, the response rate is lower than 30% in patients with cervical cancer (CC), which is related to immunosuppressive components in tumor microenvironment (TME). Tumor-associated macrophages (TAMs), as one of the most important immune cells, are involved in the formation of tumor suppressive microenvironment. Therefore, it will provide a theoretical basis for curative effect improvement about the regulatory mechanism of TAMs on PD-L1 expression. METHODS: The clinical data and pathological tissues of CC patients were collected, and the expressions of PD-L1, CD68 and CD163 were detected by immunohistochemistry. Bioinformatics was used to analyze the macrophage subtypes involved in PD-L1 regulation. A co-culture model was established to observe the effects of TAMs on the morphology, migration and invasion function of CC cells, and the regulatory mechanism of TAMs on PD-L1. RESULTS: PD-L1 expression on tumor cells could predict the poor prognosis of patients. And there was a strong correlation between PD-L1 expression with CD163+TAMs infiltration. Similarly, PD-L1 expression was associated with M1/M2-type TAMs infiltration in bioinformatics analysis. The results of cell co-culture showed that M1/M2-type TAMs could upregulate PD-L1 expression, especially M2-type TAMs may elevate the PD-L1 expression via PI3K/AKT pathway. Meanwhile, M1/M2-type TAMs can affect the morphological changes, and enhance migration and invasion abilities of CC cells. CONCLUSIONS: PD-L1 expression in tumor cells can be used as a prognostic factor and is closely related to CD163+TAMs infiltration. In addition, M2-type TAMs can upregulate PD-L1 expression in CC cells through PI3K/AKT pathway, enhance the migration and invasion capabilities, and affect the tumor progression.

Targeted nanotherapy platform mediated tumor-infiltrating CD8+ T cell immune function effects for collaborative anti-tumor photothermal immunotherapy for cervical cancer.

Photothermal immunotherapy is an innovative approach to cancer treatment. It combines immunomodulators and photothermal agents, both targeted to the tumor site. This therapy harnesses the heat generated by photothermal conversion to damage tumor cells while simultaneously releasing tumor-associated antigens. This process enhances the anti-tumor immune response of tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment (TME). Photothermal immunotherapy is gaining prominence as a new method for cancer treatment. It is a current focal point in research due to its targeted efficacy, minimal systemic side effects, and reduced risk of treatment resistance. This study employed a thin-film dispersion method to fabricate liposomes (LIPO) as composite drug carriers. Indocyanine green (ICG) for clinical use was utilized as a photothermal agent (PTA), and folate (FA) was employed as a targeting agent for the nano-composite material. We encapsulated the immunoadjuvant CpG ODN within the FA@LIPO@ICG nano-system, resulting in the formation of targeted nanoparticles (NPs) for photothermal immunotherapy (FA@LIPO@ICG@CpG), and assessed the drug encapsulation rate. FA@LIPO@ICG@CpG NPs demonstrated excellent water solubility with an average size ranging from 100 to 200 nm. Furthermore, we investigated the photothermal properties of FA@LIPO@ICG@CpG NPs. Under 808 nm laser irradiation, the photothermal conversion efficiency of FA@LIPO@ICG@CpG NPs reached 39.05%. Subsequently, under 808 nm laser excitation, we conducted an analysis of lymphocyte subpopulations and their functional changes in U14 tumor-bearing mice by using flow cytometry. This treatment approach demonstrated remarkable anti-tumor efficacy. Consequently, FA@LIPO@ICG@CpG NPs hold substantial promise as a novel and promising strategy in cancer therapy.

Long non-coding RNA Linc00657 up-regulates Skp2 to promote the progression of cervical cancer through lipid reprogramming and regulation of immune microenvironment.

More and more evidence shows that long non-coding RNA (lncRNA) plays an important role in the biological behavior of many kinds of malignant tumors, but the specific function of lncRNA Linc00657 in cervical cancer is still unknown. The purpose of this study is to explore the effect of Linc00657 on the malignant progression of cervical cancer and its potential mechanism. In two kinds of cervical cancer cell lines and normal cervical epithelial cells, qRT-PCR showed increased expression of Linc00657 in cervical cancer cells. Through MTT, clone formation test, flow cytometry, wound healing test and Transwell test, it has been found that overexpression of Linc00657 could promote the proliferation,migration and invasion of cervical cancer cells，and inhibit apoptosis. Through the StarBase database, it was found that there may be a mutual regulatory relationship between Linc00657 and Skp2, and Skp2 may be the downstream target of Linc00657. QRT-PCR detection confirmed that the expression of Skp2 was increased in cervical cancer cells with overexpression of Linc00657. TIMER2 database found that Skp2 was associated with lipid metabolic enzymes and immune cell infiltration. It was found that Linc00657 knockdown inhibited tumor growth and metastasis and inhibited the expression of Skp2 in vivo. In short, our research shows that Linc00657 has carcinogenic properties in cervical cancer, and LINC00657 promotes the occurrence of cervical cancer by up-regulating the expression of Skp2. We predict that Linc00657/mir30s/Skp2 axis plays a role in the malignant progression of cervical cancer. In addition, Skp2 may participate in cancer immune response and promote lymph node metastasis of cervical cancer through lipid reprogramming. These findings also provide promising targets for the diagnosis and treatment of cervical cancer.

Comparison of 3D and 2D laparoscopy: Initial experience of perioperative outcomes and clinical assessment.

INTRODUCTION: This study was designed to compare three-dimensional (3D) laparoscopy and conventional two-dimensional (2D) laparoscopy in surgical performance and clinical assessment during laparoscopic radical hysterectomy with pelvic lymphadenectomy (LRHND) for treating early-stage cervical cancer. MATERIAL AND METHODS: In this study, we included 67 consecutive patients underwent LRHND for treating early-stage cervical cancer by the experienced laparoscopic surgeons between August 2018 and December 2020. amongst these patients, 32 patients underwent 3D laparoscopy (2D group) and 35 patients underwent 2D laparoscopy (2D group). Demographic data, clinical and surgical parameters were obtained from each patient. An end-of-operation questionnaire was administered regarding subjective perception of 3D laparoscopy system. RESULTS: Patient characteristics, including age, BMI, FIGO stage, and histology, were comparable between the two groups. Compared with 2D imaging system, 3D system significantly shortened the operation time, especially bilateral lymph node dissection time. Blood loss was lower in 3D group compared with 2D group. There were no significant differences regarding pelvic nodes retrieved, incidence of complications, hospital stay, the recovery time of bowel, abdominal drainage fluid, hospitalization costs and visual symptoms. In addition, 3D system significantly improved depth perception and precision, and reduced surgical strain and eye strain for surgeon. No statistical difference was observed in visual symptoms and adverse events between the two groups. The surgeon was more willing to accept 3D laparoscopy. CONCLUSION: The 3D laparoscopy is safe, feasible and comfortable, with obvious advantage in depth perception, precision and surgical strain. It triggered no increase in the complications and adverse events.

Establishment of prediction models to predict survival among patients with cervical cancer based on socioeconomic factors: a retrospective cohort study based on the SEER Database.

OBJECTIVE: To construct and validate predictive models based on socioeconomic factors for predicting overall survival (OS) in cervical cancer and compare them with the American Joint Council on Cancer (AJCC) staging system. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We extracted data from 5954 patients who were diagnosed with cervical cancer between 2007 and 2011 from the Surveillance, Epidemiology, and End Results Database. This database holds data related to cancer incidence from 18 population-based cancer registries in the USA. OUTCOME MEASURES: 1-year and 5-year OS. RESULTS: Of the total 5954 patients, 5820 patients had 1-year mortality and 5460 patients had 5-year mortality. Lower local education level [Hazard ratios (HR): 1.15, 95% confidence interval (CI): 1.04 to 1.27, p= 0.005] and being widowed (HR 1.28, 95% CI 1.06 to 1.55, p=0.009) were associated with a worse OS for patients with cervical cancer. Having insurance (HR 0.75, 95% CI 0.62 to 0.90, p=0.002), earning a local median annual income of ≥US$56 270 (HR 0.83, 95% CI 0.75 to 0.92, p<0.001) and being married (HR 0.79, 95% CI 0.69 to 0.89, p<0.001) were related to better OS in patients with cervical cancer. The predictive models based on socioeconomic factors and the AJCC staging system had a favourable performance for predicting OS in cervical cancer compared with the AJCC staging system alone. CONCLUSION: Our proposed predictive models exhibit superior predictive performance, which may highlight the potential clinical application of incorporating socioeconomic factors in predicting OS in cervical cancer.

Survey on cervical cancer knowledge and its influencing factors among 2,578 women in Shache county, Kashi, China.

BACKGROUND: In the southern part of Xinjiang, the incidence and mortality rates of the cervical cancer among Uyghurs are significantly higher than those of other ethnic groups living in the same environment, and their mortality rate takes the first place among ethnic minorities in China. OBJECTIVE: To assess the level of cervical cancer knowledge by Questionnaire survey using the scoring system and its influencing factors among women in Shache county, Kashi, China. METHOD: Based on the cervical cancer health education carried out by the medical team of the county hospital to the residents in the urban and rural areas of Shache County from September 1st, 2022, to September 30th, 2022, a cluster sampling was conducted at the same time and a total of 2578 women were included. The questionnaire survey includes resident basic information, and their knowledge about cervical cancer which was evaluated by the scoring system. The scoring system of the knowledge about cervical cancer includes 4 items, the total score was 8 point and scored more than 4 points was used as knowledge knowing, the knowledge of cervical cancer (unknown = 0; known = 1) was used as the dependent variable. Six factors include residence area (urban or rural), age, ethnic group, educational level, occupation, and the ways to acquire knowledge access were used as independent variables. The retrieved questionnaire was entered by the medical staff, and the Excel software was used for duplicate verification. Chi-square test and unconditional logistic regression analysis were used for statistical analysis. RESULTS: Of the 2578 study subjects, 1591 were from rural areas and 987 were from the urban areas, and the differences were statistically significant (P < 0.001). Based on the scoring system of the knowledge about cervical cancer, the knowledge knowing accounts for only 34.1%. Multivariate logistic regression analysis showed that living in the urban(AOR = 1.358,95% CI:1.111-1.659), occupation of non-farming and non-housewife(AOR = 2.680,95%CI:2.126-3.377), education level of high school and above(AOR = 1.388,95%CI:1.125-1.712), and four or more access to knowledge(AOR = 1.446,95%CI:1.099-1.903) were protective factors for cervical cancer knowledge knowing. CONCLUSION: Based on the questionnaire survey, the level of cervical cancer knowledge among women in Shache county was inadequate. Considering above mention influencing factors, it is necessary for the medical and health institutions to take various measures to carry out targeted health education on cervical knowledge for women in Shache county.

Early screening of cervical cancer based on tissue Raman spectroscopy combined with deep learning algorithms.

Cervical cancer is the most common reproductive malignancy in the female reproductive system. The incidence rate and mortality rate of cervical cancer among women in China are high. In this study, Raman spectroscopy was used to collect tissue sample data from patients with cervicitis, cervical precancerous low-grade lesions, cervical precancerous high-grade lesions, well differentiated squamous cell carcinoma, moderately differentiated squamous cell carcinoma, poorly differentiated squamous cell carcinoma and cervical adenocarcinoma. The collected data were preprocessed using an adaptive iterative reweighted penalized least squares (airPLS) algorithm and derivatives. Convolutional neural network (CNN) and residual neural network (ResNet) classification models were constructed to classify and identify seven types of tissue samples. The attention mechanism efficient channel attention network (ECANet) module and squeeze-and-excitation network (SENet) module were combined with the established CNN and ResNet network models, respectively, to make the models have better diagnostic performance. The results showed that efficient channel attention convolutional neural network (ECACNN) had the best discrimination, and the average accuracy, recall, F1 and AUC values after five cross-validations could reach 94.04%, 94.87%, 94.43% and 96.86%, respectively.

New insights on the interaction between m6A modification and non-coding RNA in cervical squamous cell carcinoma.

BACKGROUND: N6-Methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are both crucial regulators in human cancer growth and metastasis. However, their regulation on cervical squamous cell carcinoma (CSCC) is largely unclear. The present study aimed to explore the role of m6A-associated lncRNAs in CSCC. METHODS: We screened the expression of methylation modification-related enzymes in CECC samples from TCGA. The qRT-PCR was used to detect METTL3 and lncRNA METTL4-2 expression. The biological activities of METTL3 in CSCC cells were evaluated by CCK-8, colony formation, transwell, wound healing, and xenograft tumor assays, respectively. The SRAMP tool was used to screen m6A modification sites of METTL4-2. Finally, the quantitative analysis of m6A modification was carried out by MeRIP. RESULTS: METTL3 expression was upregulated in CSCC cells and tissues. Biological function and function loss analysis indicated that METTL3 promoted the migration and proliferation of CSCC cells. In addition, METTL3 promoted CSCC tumor growth in vivo. Mechanically, METTL3 installed the m6A modification and enhanced METTL4-2 transcript stability to increase its expression. Meanwhile, the m6A "reader" YTHDF1 recognized METTL4-2 installed by METTL3 and facilitated the translation of METTL4-2. CONCLUSIONS: In conclusion, our study highlights the function and mechanism of METTL3-induced METTL4-2 in CSCC. These findings support that METTL3-stabilized METTL4-2 promoted CSCC progression via a m6A-dependent modality, which provides new insights into therapeutic strategies for CSCC.

Clinical indocyanine green-based silk fibroin theranostic nanoprobes for in vivo NIR-I/II fluorescence imaging of cervical diseases.

Cervical diseases such as lymph node disease and tubal obstruction have threatened women's health. However, the traditional diagnostic methods still have shortcomings. NIR-II fluorescence imaging with advantages of low scattering, negligible autofluorescence, and high spatial resolution could be an ideal option. To obtain high quality NIR-II fluorescence imaging, selecting appropriate nanoprobes becomes the important issue. As a small molecular photothermal agent, extensive applications of ICG are rather limited because of its drawbacks. Herein, natural silk fibroin (SF) was synthesized and encapsulated ICG molecules to form SF@ICG nanoparticles (NPs). After detailed analysis, SF@ICG NPs showed excellent stability and long circulation time, as well as strong NIR-II fluorescence emission, well photo-stability, biocompatibility and well photothermal property under 808 nm laser irradiation. Furthermore, SF@ICG NPs were utilized for NIR-II fluorescence imaging of lymph node/lymphangiography and angiography of fallopian tubes. The process of fallopian tubes could be detected with high resolution and high sensitivity.

Circulating tumor cells correlating with Ki-67 predicts the prognosis of bladder cancer patients.

PURPOSE: To investigate the value of circulating tumor cells (CTCs) and Ki-67 in predicting the prognosis of bladder cancer. Here, we tested CTC counts and Ki-67 levels to assess patient prognosis. METHODS: 84 patients with bladder cancer who underwent surgery were included in this study. Peripheral blood CTCs were detected by SE-iFISH technology before and after surgery, and Ki-67 levels were analyzed by immunohistochemistry. The association between CTCs and Ki-67 and the combination of the two was analyzed to predict the prognosis of patients. RESULTS: 76 out of 84 patients (90.5%) were positive. ROC curve analysis showed that preoperative and postoperative CTC counts = 4 and 2 were the best thresholds for predicting patient recurrence or death. In multivariate analysis, high postoperative CTC count (≥ 2) (P < 0.001) and Ki-67 high expression (≥ 15%) (P < 0.001) were independent poor prognostic factors for PFS in bladder cancer patients. In addition, the study found that Ki-67 levels were positively correlated with high postoperative CTC counts, Bladder cancer patients with Ki-67 high expression and high postoperative CTC counts were associated with extremely poor progression-free survival. CONCLUSION: Ki-67 high expression is associated with high postoperative CTC counts, both of which predict poor prognosis in bladder cancer patients.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

Characteristics of Vaginal Microbiome in Reproductive-Age Females with HPV Infection in Xinjiang, China.

Objective: We investigated the characteristics of vaginal microbiome in reproductive-age females with HPV infection in Xinjiang, China. Methods: A total of 135 females of reproductive age were enrolled. There were 43 healthy HPV-negative females in control group (N group), 58 HPV-positive females in nonlesion group (P1 group), and 34 HPV-positive females in low-grade squamous intraepithelial lesion group (P2 group). DNA was extracted from the vaginal secretions, and V3-V4 regions of bacterial 16S rDNA were amplified and sequenced by NovaSeq. QIIME2 and R software were used to perform diversity analysis of bacteria. PICRUSt2 was used to predict the function of the vaginal microbiota. Results: Lactobacillus was the main genus of vaginal microbiota in asymptomatic reproductive-age females with or without HPV in Xinjiang. The diversity of vaginal microbiota in the P1 group was significantly higher than that in the N group, and the proportion of Gardnerella increased significantly. The vaginal microbiota structure of the P2 group was different from the N group, characterized by the decrease of Lactobacillus crispatus and the increase of Shuttleworthia. The function of the inordinate microbiome may play a role in accelerating HPV replication and integration. Conclusion: The structure of vaginal microbiota alters under persistent HPV infection in asymptomatic females of reproductive age in Xinjiang. The Gardnerella increase is associated with increased susceptibility to HPV infection, and Lactobacillus iners predominance and Shuttleworthia presence may be a signature of HPV infection with low-grade squamous intraepithelial lesion.

A highly efficient polydopamine encapsulated clinical ICG theranostic nanoplatform for enhanced photothermal therapy of cervical cancer.

Photothermal therapy (PTT) is a safe and efficient anti-tumor treatment. A photothermal agent (PTA) with good biocompatibility and strong photothermal properties is of great importance for PTT. In this study, near-infrared (NIR) excitable clinical indocyanine green (ICG) was utilized as a PTA and further encapsulated by another PTA polydopamine (PDA) to form highly stable and efficient ICG@PDA nanoparticles (NPs). Then the ICG@PDA NPs were modified with methoxy polyethylene glycol amine (mPEG2000-NH2) to form biocompatible ICG@PDA@PEG NPs. ICG@PDA@PEG NPs showed good water solubility and a spherical shape with an average size of 140 nm. Furthermore, the photothermal properties of ICG@PDA@PEG NPs were studied and excellent photothermal performance with a photothermal conversion efficiency of 43.7% under 808 nm laser irradiation was achieved. Then, the PTT properties of ICG@PDA@PEG NPs were confirmed on HeLa cells with an efficiency of 86.1%. Meanwhile, the in vivo biocompatibility and toxicity of ICG@PDA@PEG NPs were evaluated. No apparent in vivo toxicity was observed in 24 hours and 7 days. Next, in vivo PTT analysis was conducted for cervical tumor-bearing nude mice under 808 nm laser excitation. It showed a good anti-tumor effect in vivo. Thus, ICG@PDA@PEG NPs exhibited great potential for safe and efficient photothermal therapy in anti-tumor therapy.

Low Tumor Infiltrating Mast Cell Density Reveals Prognostic Benefit in Cervical Carcinoma.

Objectives: Research on the role of mast cells (MCs) in cervical tumor immunity is more limited. Therefore, our study aimed to evaluate the prognostic value of MCs and their correlation with the immune microenvironment of cervical carcinoma (CC). Methods: The Cancer Genome Atlas (TCGA) data was utilized to obtain the degree of immune infiltration of MCs in CC. Meanwhile, this study retrospectively collected patient clinical characteristic data and tissue specimens to further verify the relevant conclusions. Mast cell density (MCD) was measured by the CIBERSORT algorithm in TCGA data and immunohistochemical staining of tryptase in CC tissues. Finally, differentially expressed genes (DEGs) of TCGA data were performed using "limma" packages and key gene modules were identified using the MCODE application in Cytoscape. Results: The results showed MCs were diffusely distributed in CC tissues. Moreover, we found that low tumor-infiltrating MCD was beneficial for overall survival (OS) in the TCGA cohort. Consistent conclusions were also obtained in a clinical cohort. In addition, a total of 305 DEGs were analyzed between the high tumor-infiltrating MCD and low tumor-infiltrating MCD group. Seven key modules, a total of 34 genes, were screened through the MCODE plug-in, which was mainly related to inflammatory response and immune response and closely correlated with cytokines including CSF2, CCL20, IL1A, IL1B, and CXCL8. Conclusion: In short, high tumor-infiltration MCs in CC tissue was associated with worse OS in patients. Furthermore, MCs were closely related to cytokines in the tumor microenvironment, suggesting that they collectively played a role in the immune response of the tumor. Therefore, MCD may be a potential prognostic indicator and immunotherapy target of CC.

Expression and correlation analysis of Skp2 and CBX7 in cervical cancer.

AIMS: S-phase kinase-associated protein 2 (Skp2) oncoprotein is overexpressed in a variety of cancer tissues and promotes the malignant development of cancer. The expression levels of chromobox homolog 7 (CBX7) protein are varied among different types of cancer tissues, but its role in cervical cancer is not clear. We aimed to examine the expression and clinical significance of Skp2 and CBX7 proteins as well as their correlations in cervical cancer. METHODS: Immunohistochemistry was used to detect the expression of Skp2 and CBX7 proteins in the cancerous tissues and adjacent tissues of 64 patients with cervical cancer. Relevant clinicopathological data of these patients were collected, compared and analysed for the correlations. RESULTS: The expression of Skp2 protein in cervical cancer (87.5%) was higher than that in paracancerous tissues (14.1%), and the expression was positively correlated with clinical stage, malignant degree, lymphatic metastasis, vascular invasion and interstitial invasion. The expression of CBX7 protein in cervical cancer (48.4%) was lower than that in paracancerous tissues (96.8%), and the expression was negatively correlated with clinical stage, malignant degree, interstitial invasion, vascular invasion and lymphatic metastasis. The expression of Skp2 protein and CBX7 protein in cervical cancer tissues and adjacent tissues was negatively correlated. The expression of Skp2 and CBX7 proteins was closely related to the clinicopathological features of cervical cancer. CONCLUSIONS: CBX7 may play the role of a tumour suppressor gene in cervical cancer and provide reference value for the diagnosis and new targeted treatment of cervical cancer.

Effect of magnetite on the catalytic oxidation of polycyclic aromatic hydrocarbons in fly ash from MSW incineration: A comparative study of one-step and two-step hydrothermal processes.

Polycyclic aromatic hydrocarbons (PAHs), many of which are carcinogenic, teratogenic, and mutagenic, exist in fly ash (FA) produced from municipal solid waste incineration (MSWI). Hydrothermal treatment (HT) is an efficient approach to remove PAHs from MSWI FA. Here, magnetite (Fe3O4) was used as the catalyst and hydrogen peroxide (H2O2) as the oxidant for one-step and two-step catalytic hydrothermal methods. When the magnetite dosage increased to 15 wt%, the maximum degradation rates of PAHs were 84.36% and 92.51%, respectively; however, the toxicity equivalent quantity (TEQ) degradation rates of the PAHs both increased upon increasing the magnetite dose. At 20 wt% Fe3O4, the maximum TEQ degradation rates of the PAHs were 93.29% and 97.76%, respectively. The reaction between OH and PAHs is non-selective, which means that LMW, MMW, and HMW PAHs were all degraded. The decrease in TEQ was mainly due to the degradation of HMW PAHs, i.e., those with five rings. Under the same Fe3O4 dose, oxidant dose, and reaction time, the detoxification of PAHs by the two-step method was significantly better than that of the one-step method, possibly because the two-step method more effectively produced OH. The first step degraded more than 90% of PAHs, and the residual PAHs in the HT products of the first step limited the utilization of the oxidant during the second step. The minerals in the HT products implied that the two-step hydrothermal method not only produced more OH, which reacted with PAHs, but also generated metal-magnetite substitution, which affected its surface reactivity during heavy metal adsorption and catalysis. These results revealed that both magnetite and the two-step hydrothermal treatment degraded PAHs. 20 wt% magnetite was the optimal amount during the two-step hydrothermal catalytic oxidation of MSWI FA.

Diagnosis and treatment of uterine sarcoma: A multicenter, real-world study in western China.

ABSTRACT: A detailed understanding of the diagnosis and treatment of uterine sarcoma in the real world is required due to its low incidence, high malignancy, lack of specific symptoms, and lack of high-level evidence supporting its clinical diagnosis and treatment. This study aimed to provide a basis for the standardized diagnosis and treatment of uterine sarcoma. It retrospectively analyzed the real-world data on the diagnosis, treatment, and prognosis of uterine sarcoma in western China.The clinical and pathological data of patients with uterine sarcoma diagnosed and treated between January 2009 and January 2019 in 13 medical centers from 4 western provinces of China, Sichuan, Guangxi, Shaanxi, and Xinjiang, were collected and further examined by univariate and multivariate analyses to find possible risk factors affecting the prognosis of uterine sarcoma.A total of 299 patients with various pathological types of uterine sarcoma were included, with an average age of 47.7 ±â€Š11.1 years. The univariate and multivariate analyses showed that age (P = .0081), family history (P = .0358), and chemotherapy regimen (P = .0005) significantly correlated with progression-free survival; while age (P = .0393) and International Federation of Gynecology and Obstetrics staging (P = .0141) significantly correlated with overall survival.As age increased, the risk of death in patients with uterine sarcoma increased; The disease tended to progress faster in lower-age patients. A family history of tumors had an impact on disease progression; however, the way in which it affected needs further exploration. Different chemotherapy regimens affected the patient's disease progression. This study suggested that the anthracycline chemotherapy regimen was slightly better.

Indocyanine Green-Based Theranostic Nanoplatform for NIR Fluorescence Image-Guided Chemo/Photothermal Therapy of Cervical Cancer.

PURPOSE: Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the BSA@ICG-DOX theranostic nanoplatform. METHODS: In this study, ICG-loaded BSA nanoparticles (NPs) and the BSA@ICG-DOX NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of BSA@ICG-DOX NPs under 808 nm laser irradiation. RESULTS: The BSA@ICG NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the BSA@ICG NPs to form the BSA@ICG-DOX theranostic nanoplatform. The BSA@ICG-DOX NPs were spherical with an average size of ~194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the BSA@ICG-DOX NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice. CONCLUSION: To improve the anti-tumor efficiency of the ICG@BSA NPs, the chemotherapeutic drug DOX was loaded into the BSA@ICG NPs. The NIR excitation/emission and targeted BSA@ICG-DOX NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications.

Knockdown of NOVA1 inhibits inflammation and migration of asthmatic airway smooth muscle cells to regulate PTEN/Akt pathway by targeting PTBP1.

NOVA1 (neuro-oncological ventral antigen 1) is a neuron specific RNA binding protein, belonging to the Nova family, which plays an important role in various diseases. However, the role of NOVA1 in childhood asthma remains unclear. This study was aimed to investigate the role of NOVA1 in TGF-ß1-induced ASMCs proliferation and migration as well as the potential mechanisms. In our study, the NOVA1 expression was significantly increased in asthmatic tissues and TGF-ß1-induced ASMCs. Inhibition of NOVA1 significantly inhibited TGF-ß1-induced ASMCs cell proliferation and migration, and alleviates TGF-ß1-induced inflammation. NOVA1 positively regulated the PTBP1 expression and si-NOVA1 inhibited the activation of PTEN/AKT signal pathway. Importantly, the overexpression of PTBP1 partially reversed the effect of NOVA1 on cell viability, migration, inflammation and the activation of PTEN/AKT signal pathway. Generally, our study demonstrated that si-NOVA1 inhibited TGF-ß1-induced inflammation and migration in ASMCs through PTBP1/PTEN/AKT pathway. Therefore, inhibition of NOVA1 may be useful for the prevention or treatment of asthma airway remodeling.