Novel strategies in HPV­16­related cervical cancer treatment: An in vitro study of combined siRNA-E5 with oxaliplatin and ifosfamide chemotherapy.

BACKGROUND: Cervical cancer, primarily caused by HPV infection, remains a global health concern. Current treatments face challenges including drug resistance and toxicity. This study investigates combining E5-siRNA with chemotherapy drugs, Oxaliplatin and Ifosfamide, to enhance treatment efficacy in HPV-16 positive cervical cancer cells, targeting E5 oncoprotein to overcome limitations of existing therapies. METHODS: The CaSki cervical cancer cell line was transfected with E5-siRNA, and subsequently treated with Oxaliplatin/Ifosfamide. Quantitative real-time PCR was employed to assess the expression of related genes including p53, MMP2, Nanog, and Caspases. Cell apoptosis, cell cycle progression, and cell viability were evaluated using Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, stemness ability was determined through a colony formation assay, and cell motility was assessed by wound healing assay. RESULTS: E5-siRNA transfection significantly reduced E5 mRNA expression in CaSki cells compared to the control group. The MTT assay revealed that monotherapy with E5-siRNA, Oxaliplatin, or Ifosfamide had moderate effects on cell viability. However, combination therapy showed synergistic effects, reducing the IC50 of Oxaliplatin from 11.42 × 10-8 M (45.36 µg/ml) to 6.71 × 10-8 M (26.66 µg/ml) and Ifosfamide from 12.52 × 10-5 M (32.7 µg/ml) to 8.206 × 10-5 M (21.43 µg/ml). Flow cytometry analysis demonstrated a significant increase in apoptosis for combination treatments, with apoptosis rates rising from 11.02 % (Oxaliplatin alone) and 16.98 % (Ifosfamide alone) to 24.8 % (Oxaliplatin + E5-siRNA) and 34.9 % (Ifosfamide + E5-siRNA). The sub-G1 cell population increased from 15.7 % (Oxaliplatin alone) and 18 % (Ifosfamide alone) to 21.9 % (Oxaliplatin + E5-siRNA) and 27.1 % (Ifosfamide + E5-siRNA), indicating cell cycle arrest. The colony formation assay revealed a substantial decrease in the number of colonies following combination treatment. qRT-PCR analysis showed decreased expression of stemness-related genes CD44 and Nanog, and migration-related genes MMP2 and CXCL8 in the combination groups. Apoptosis-related genes Casp-3, Casp-9, and pP53 showed increased expression following combination therapy, while BAX expression increased and BCL2 expression decreased relative to the control. CONCLUSION: The study demonstrates that combining E5-siRNA with Oxaliplatin or Ifosfamide enhances the efficacy of chemotherapy in HPV-16 positive cervical cancer cells. This synergistic approach effectively targets multiple aspects of cancer cell behavior, including proliferation, apoptosis, migration, and stemness. The findings suggest that this combination strategy could potentially allow for lower chemotherapy doses, thereby reducing toxicity while maintaining therapeutic efficacy. This research provides valuable insights into targeting HPV E5 as a complementary approach to existing therapies focused on E6 and E7 oncoproteins, opening new avenues for combination therapies in cervical cancer treatment.

Comparative analysis between ideal and real cervical cancer screening in the city of Rio de Janeiro / Análise comparativa entre os rastreamentos ideal e real do câncer de colo uterino no município do Rio de Janeiro

Objective: to compare the number of planned oncotic smear tests and those actually performed in the city of Rio de Janeiro between the years 2013 and 2022 . Methods: using the female population of Rio de Janeiro, an estimate was made of how many tests should be carried out if screening recommended by the Ministry of Health was done in an ideal way and was subsequently compared with the number of tests available in the public database. Results: 1,364,325 were carried out in this period compared to an estimated 7,886,720. After adjustment for the use of supplementary healthcare, the pandemic and exams outside the recommended age, 36% of the ideal was observed. Conclusion: the quantity carried out is far below ideal, even after adjustments, which increases costs for the public health service, making new public policies necessary to improve tracking.

Objetivo: comparar el número de citologías oncóticas planificadas y las realizadas en la ciudad de Río de Janeiro entre los años 2013 y 2022 . Métodos: utilizando la población femenina de Río de Janeiro, se estimó cuántas pruebas se deberían realizar si se recomienda el tamizaje. realizado por el Ministerio de Salud se realizó de manera ideal y luego se comparó con la cantidad de pruebas disponibles en la base de datos pública. Resultados: En este periodo se realizaron 1.364.325 frente a una estimación de 7.886.720. Después del ajuste por el uso de asistencia sanitaria complementaria, la pandemia y los exámenes fuera de la edad recomendada, se observó el 36% del ideal. Conclusión: la cantidad realizada está muy por debajo de lo ideal, incluso después de ajustes, lo que aumenta los costos para el servicio público de salud, haciendo necesarias nuevas políticas públicas para mejorar el seguimiento.

Objetivo: comparar a quantidade de colpocitologias oncóticas ideias e a realmente realizadas no município do Rio de Janeiro entre os anos de 2013 e 2022. Métodos: através da população feminina do Rio de Janeiro, foi feita estimativa de quantos exames deveriam ser realizados caso o rastreio preconizado pelo Ministério da Saúde fosse feito de forma ideal e posteriormente foi comparado com a quantidade de exames disponíveis na base de dados pública. Resultados: foram realizados 1.364.325 nesse período comparado a 7.886.720 estimados. Após ajuste pelo uso de saúde suplementar, pandemia e exames fora da idade recomendada, observou-se 36% do ideal. Conclusão: a quantidade realizada está muito abaixo da ideal, mesmo após os ajustes, o que aumenta custos para o serviço de saúde pública, sendo necessárias novas políticas públicas para melhorar o rastreamento.

Pharmacokinetics and pharmacodynamics of angiogenesis inhibitors used to treat cervical cancer: current and future.

INTRODUCTION: The treatment of advanced cervical cancer is continuously developing. There is a critical need to explore new treatment options to improve cure rates and make treatment more affordable. Despite efforts in prevention, cervical cancer remains the fourth most common cancer worldwide in terms of both incidence and mortality. AREAS COVERED: This article offers an updated and critical analysis of angiogenesis inhibitors used in the treatment of advanced cervical cancer. It should be noted that this is not a systematic review. EXPERT OPINION: Bevacizumab is currently the primary antiangiogenic agent used alongside chemotherapy and has become the standard of care for advanced cervical cancer. However, there are still uncertainties regarding the molecular mechanisms and associations in cervical cancer that could help in optimizing the use of Bevacizumab. Factors such as cost, toxicity, and methodological issues in the GOG-240 trial must be considered.

Aptima HPV Genotypes in Abnormal Cervical Samples in Different Age Groups - Implication on Vaccination Strategies.

Context: Persistent infection with high-risk human papillomavirus (hr-HPV) types is associated with high-grade cervical abnormalities. Aims: The aim of the study was to find most hr-HPV types causing persistent infection in abnormal cytological samples using Aptima HPV testing and discuss the compatibility of the Gardasil 9 vaccine in targeting most types. Settings: The study was conducted in a cytology laboratory in a tertiary hospital. Design: This is a retrospective observational study. Methods and Materials: Cytology and HPV Aptima test reports were obtained for abnormal cervical samples for a 6-year period. Statistical Analysis Used: Pearson Chi-square test. Results: Reports of 2834 abnormal cervical samples were analyzed. Aptima testing was positive in 21% of samples, including 92% of squamous cell carcinoma (SCC), 76.4% of the high-grade squamous intraepithelial lesion (HSIL), 52% of low-grade squamous intraepithelial lesion (LSIL), 40% of adenocarcinoma (ADC), and 21% of atypical squamous cells that cannot exclude HSIL (ASC-H). The Aptima other hr-HPV group was most common (60%), HPV16 was 26%, HPV18/45 was 9.6%, and double HPV infection was 4.3%. HPV16 was the most common infection in HSIL+ cases. HPV infection was most common in age groups (30-39) and (40-49), and a shift to age groups (50-59) and ≥60 was seen in HSIL+ cases. Conclusions: This study is the first of its kind in correlating age with hr-HPV and cytology findings in the Middle East and adds to previous knowledge related to the prevalence and Aptima testing of HPV. The outcome could be used as a baseline for the Gardasil 9 vaccine and for the assessment of its effectiveness after three or five years from initiation.

Adoption strategies of fertility-sparing surgery for early-stage cervical cancer patients based on clinicopathological characteristics: a large retrospective cohort study.

Background: The demand for fertility-sparing surgery (FSS) is increasing among patients with early-stage cervical cancer (CC). This study aimed to evaluate the feasibility of local excision as an alternative to hysterectomy in stage I CC patients aged 15-39 years-commonly referred to as adolescents and young adults (AYAs)-with varying clinicopathological characteristics. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed between 2000 and 2020. We examined treatment interventions across different age groups, degrees of histological types, tumor differentiation, and tumor stages. The effect of local excision vs. hysterectomy was assessed by comparing overall survival (OS) and disease-specific survival (DSS) rates. Results: A total of 10,629 stage I AYA cervical cancer patients were included in this study. Among these patients, 24.5% underwent local excision for fertility preservation, while 67.3% underwent radical hysterectomy. For patients with cervical squamous cell carcinoma (SCC), long-term outcomes favored local excision over hysterectomy, and a similar trend was observed in those with adenosquamous cell carcinoma (ASCC). However, the prognosis was comparable among patients with cervical adenocarcinoma (AC). In patients with well- and moderate- differentiated tumors, local excision demonstrated superior OS compared to hysterectomy. No significant differences in prognosis were found between the two surgical interventions for patients with poorly differentiated and undifferentiated tumors. In stage IA patients, local excision was considered a viable alternative to hysterectomy. In stage IB1-IB2, FSS yielded prognostic outcomes comparable to those of hysterectomy. Conversely, patients with stage IB3 exhibited significantly shorter 5-year OS and DSS following local excision than those who underwent hysterectomy. Conclusion: In stage IA-IB2 (diameter ≤4 cm) AYA patients, local excision may serve as a viable option for fertility preservation. The histological type of SCC, AC, and ASCC, along with differentiation, should not serve as restrictive factors in determining fertility preservation strategies for these patients. Patients with early-stage, well- or moderately-differentiated SCC may benefit from local excision surgery, even when fertility preservation is not the primary objective.

The effectiveness of cervical transforaminal epidural steroid injections for the treatment of cervical radicular pain: A prospective cohort study reporting 12-month outcomes.

Objectives: To evaluate the effectiveness of cervical transforaminal epidural steroid injection (CTFESI) for the treatment of unilateral cervical radicular pain. Design: Single-group prospective cohort study. Methods: Outcomes included ≥50% reductions in Numeric Rating Scale (NRS) for arm pain, ≥30% Neck Disability Index (NDI-5) improvement, health-related quality of life (EQ-5D), global improvement (PGIC), personal goal achievement (COMBI), Chronic Pain Sleep Index (CPSI), and healthcare utilization at one, three, six, and 12 months. Data analysis included descriptive statistics with the calculations of 95% confidence intervals (CIs), contingency table analysis, and multilevel logistic regression (LR) analysis, including a worst-case (WC) sensitivity analysis in which missing data were treated as treatment failure. Participants who were treated surgically were considered failures in the categorical analyses. Results: 33 consecutively enrolled participants (63.6% females, 51.2 ± 12.2 years of age, BMI 28.3 ± 4.5 kg/m2) were analyzed. Success rates for ≥50% reduction in NRS for arm pain at one, three, six and 12 months were 57.6% (95% CI 40.8-72.8%), 71.9% (95% CI 54.6-84.4%), 64.5% (95% CI 46.9-78.9%), and 64.5% (95% CI 46.9-78.9%). Success rates for ≥30% improvement in NDI-5 were 60.6% (95% CI 43.7-75.3%), 68.8% (95% CI 51.4-82.0%), 61.3% (95% CI 43.8-76.3%), and 71.0% (95% CI 53.4-83.9%). In WC analysis, success rates for ≥50% arm NRS and NDI-5 were 0-4.3% lower between 1 and 12 months. PGIC scores were at least "much improved" or "very much improved," in 48.4-65.6% of participants between 1 and 12 months. 6.1%, 6.1%, and 3.0% had one, two, or three repeat injections, respectively. 18.2% of participants underwent surgery by 12 months. Participants showed significant improvements in arm NRS and NDI-5 after treatment (p < 0.05), multilevel logistic regression models showed no significant decline in improvements across the follow-up time points (p > 0.05). Conclusion: Statistically significant and clinically meaningful improvements in pain and disability were observed after CTFESI for up to 12 months in individuals with unilateral cervical radicular pain.

Metal-organic cage as a theranostic nanoplatform for magnetic resonance imaging guided chemodynamic therapy.

Rationale: Theranostic nanoplatforms exert a vital role in facilitating concurrent real-time diagnosis and on-demand treatment of diseases, thereby making contributions to the improvement of therapeutic efficacy. Nevertheless, the structural intricacy and the absence of well-defined integration of dual functionality persist as challenges in the development of theranostic nanoplatforms. Methods: We develop an atomically precise theranostic nanoplatform based on metal-organic cage (MOC) to provide magnetic resonance imaging (MRI) guided chemodynamic therapy (CDT) for cancer therapy and assess the theranostic performance both in vitro and in vivo. Through UV-vis spectroscopy, electron paramagnetic resonance (EPR), confocal microscopy, flow cytometry, immunofluorescence staining, and western blotting, the ability of MOC-Mn to generate •OH and the subsequent inhibition of HeLa cells was confirmed. Results: The MOC-Mn composed of manganese and calixarene was successfully synthesized and comprehensively characterized. The catalytic activity of manganese within MOC-Mn facilitated the efficient generation of hydroxyl radicals (•OH) through a Fenton-like reaction, leveraging the high concentrations of hydrogen peroxide in the tumor microenvironment (TME). Additionally, its capacity to prolong the T1 relaxation time and augment the MR signal was observed. The theranostic efficacy was verified via rigorous in vitro and in vivo experiments, indicating that MOC-Mn offered clearer visualization of tumor particulars and substantial suppression of tumor growth. Conclusion: This study showcases a precise MRI-guided CDT theranostic nanoplatform for cancer therapy, thereby promoting the advancement of precise nanomedicine and structure-function research.

Effectiveness of early cervical functional exercise in patients after anterior cervical discectomy and fusion: A randomized controlled trial.

OBJECTIVE: To observe the effect of early cervical functional exercise (CFE) on clinical outcomes and safety of patients after anterior cervical discectomy and fusion (ACDF). METHODS: Sixty patients who underwent ACDF from September 2019 to September 2020 were analyzed and randomly divided into two groups: the CFE group (27 cases) and the usual care (UC) group (33 cases). Then, all patients in the two groups received routine postoperative guidance care at the same time. Besides, the patients of the CFE group underwent a cervical functional exercise program after on the third day after ACDF. The evaluation was conducted preoperatively and at 1 week, 1 month and 6 months after surgery. The Visual Analogue Scale (VAS), Neck Disability Index (NDI) and Japanese Orthopaedic Association scores (JOA) were used to assess clinical outcomes and the safety was confirmed with routine postoperative radiological visits to ensure intervertebral stability. RESULTS: The CFE group reported lower neck pain scores on VAS at 1 month after surgery (P = 0.02) and higher postoperative scores by JOA at 1 month and 6 months, neck disability on NDI at 1 week, 1 month and 6 months after surgery (P < 0.05) compared to the UC group. For postoperative dysfunction, the CFE group had more significant changes than the UC group at 1 month and 6 months after surgery (P < 0.05). There was no statistical difference in cervical curves, fusion rate and fusion status between the two groups, and no revision surgery was recorded although a patient has one screw partially back out in UC group. CONCLUSION: Our study suggested that the cervical functional exercise could decrease cervical pain and improve postoperative function in patients after ACDF. It was a safe and effective treatment for postoperative rehabilitation. The use of a postoperative collar, especially for one or two-level ACDF may not be needed. PROTOCOL IDENTIFYING NUMBER: This trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1900025569) on 01/09/2019.

3D-printed individual template brachytherapy for the treatment of intractable central pelvic recurrent cervical cancer: A single institution experience.

OBJECTIVE: The prognosis of recurrent cervical cancer tends to be poor and there are limited effective treatments currently available for these patients. This study was developed to find a safe and effective treatment for patients with central pelvic recurrent cervical cancer. MATERIALS AND METHODS: This retrospective study analyzed patients with central pelvic recurrent cervical cancer who received 3D-printed individual template (3D-PIT) brachytherapy between February 2019 and June 2023. Analyses of dosimetric parameters, toxicity-related complications, and survival were conducted based on the data of these patients. RESULTS: Twenty-one patients with central pelvic recurrent cervical cancer patients were enrolled. All of them received 3D-printed individual template (3D-PIT) brachytherapy. The mean respective adjusted cumulative HRCTV-D90 and HRCTV-D98 values for these patients were 86.9 Gy and 75.4 Gy. And the local control (LC) rate of these patients was 57.1%. In these 21 patients, only 2 (9.5%) of them experienced grade 3-4 rectal adverse reactions, while 7 (33.3%) patients experienced grade 3-4 bladder adverse reactions. 5(23.8%) patients had fistula, while 3 of these 5 patients had undergone prior anti-VEGF targeted drug treatment which is a risk factor of fistula. The respective 2-year rates of overall and progression-free survival (OS and PFS) for these patients were 72.9% and 57.4%, with a 26-month median PFS. CONCLUSIONS: These single-institution data highlight the potential viability of 3D-PIT brachytherapy as an approach to managing intractable central pelvic recurrent cervical cancer following first-line treatment.

A Review of Human Papillomavirus Vaccination and Associated Ethical Concerns.

Since its Fast-Track approval by the Federal Drug Administration, the human papillomavirus (HPV) vaccine has been marked by controversies. Unconfirmed reports of adverse events in both Japan and Denmark led to suspensions of national vaccination programs, which setback the fight against cervical cancer and associated mortality and morbidity. Despite follow-up studies of vaccine adverse reports, additional randomized control trials, and review reports from both the World Health Organization and the European Commission, there is still a great deal of hesitancy around the vaccine. While all three version of the HPV vaccine have been shown to be efficacious and safe, additional ethical dilemmas deserve to be considered as well.

Traditional female cervical cauterization and risk of preterm birth in Somalia: a single-center prospective observational study.

Numerous traditional practices are both beneficial and harmful. Traditional harmful practices, such as female genital mutilation and traditional cervical cauterization, are carried out for a number of reasons but can have negative health and social effects. In addition to deeply held beliefs, a lack of knowledge and awareness of the consequences of these practices contributes to the persistence of these issues. The objective of this study is to examine whether traditional cervical cauterizations were associated with preterm births in Somalia. This prospective cohort study was conducted at our hospital over a one-year period. Seven hundred and two patients were included in this study; these patients were divided into two groups, cauterized and non-cauterized groups, and the two groups were compared on pregnancy outcomes. We examined whether traditional cervical cauterizations were associated with adverse pregnancy outcomes, including preterm births. According to the findings of this study, traditional cervical cauterization was prevalent among patients visiting MSTREH (n = 328, 46.7%). Infections of the uterine cervix and infertility were the two main indications for cauterization, 44.8%, and 34.8%, respectively.Being older, uneducated, and poverty were significantly associated with traditional cauterization (P < 0.001). There was a significant correlation between prior traditional cervical cauterization and the risk of preterm births. Women with prior cauterization were two and half times more likely to deliver a preterm fetus (OR: 2.64, 95% CI 2.15-3.33) compared to non-cauterized mothers. Our findings show that women who have previously undergone traditional cervical cauterization have a significantly higher risk of preterm birth and negative pregnancy outcomes than non-cauterized women. Health professionals, particularly those who are close to the community, are crucial in developing and putting into practice plans to end harmful traditions in Somalia.

The controlling nutritional status score as a new prognostic predictor in patients with cervical cancer receiving radiotherapy: a propensity score matching analysis.

BACKGROUND: As assessment tools of nutritional status, the controlling nutritional status (CONUT) and modified controlling nutritional status (mCONUT) score are associated with survival in various cancers. We aimed to investigate the association between the CONUT/mCONUT score's prognostic value and survival time in patients with FIGO stage IIB-IIIB cervical cancer treated with radiotherapy. METHODS: In this retrospective study, 165 patients between September 2013 and September 2015 were analyzed, and the optimal CONUT/mCONUT score cut-off values were determined using receiver operating characteristic curves. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan-Meier method and a Cox proportional hazard model were used to assess the CONUT/mCONUT score's predictive value linked to survival time. Two nomograms were created to predict the overall survival (OS) and progression-free survival (PFS). RESULTS: The cut-off values for CONUT and mCONUT score were both 2. Five-year OS and PFS rates were higher in a low CONUT score group than in a high CONUT score group (OS: 81.1% vs. 53.8%, respectively, P < 0.001; PFS: 76.4% vs. 48.2%, respectively; P < 0.001). A high CONUT score was associated with decreased OS (hazard ratio (HR) 2.93, 95% CI 1.54-5.56; P = 0.001) and PFS (HR 2.77, 95% CI 1.52-5.04; P < 0.001). High CONUT scores influenced OS in the PSM cohort. A high mCONUT score was not associated with decreased OS and PFS in Cox regression analysis. CONCLUSION: The CONUT score is a promising indicator for predicting survival in patients with cervical cancer receiving radiotherapy.

MRI-based assessment paraspinal extensor muscle fatty infiltration in acute cervical spinal cord injury patients - a retrospective study.

BACKGROUND: The effect of fat infiltration in the paraspinal muscles on cervical degenerative disease has been confirmed by multiple studies. However, little is known about fat infiltration in the paraspinal extensors in patients with acute cervical spinal cord injury (SCI). This study aimed to investigate the difference in paraspinal extensor fatty infiltration between patients with acute cervical SCI and healthy controls, and to further explore the protective role of the paravertebral extensor muscles in patients with cervical SCI. METHODS: A total of 50 patients with acute cervical SCI admitted to the emergency department from January 2019 to November 2023 were retrospectively analyzed, including 26 males and 24 females, with an average age of 59.60 ± 10.81 years. A control group of 50 healthy middle-aged and elderly individuals was also included, comprising 28 males and 22 females, with an average age of 55.00 ± 8.21 years. Cervical spine magnetic resonance imaging (MRI) was used to measure the cross-sectional areas of the superficial and deep cervical extensor muscles, the corresponding vertebral body cross-sectional areas, and the fat area within the superficial and deep extensor muscle groups using Image J software. Differences between the two groups were compared, and the cervical SCI patients were further analyzed based on the severity of the spinal cord injury and gender differences. RESULTS: The deep fatty infiltration ratio (DFIR) and superficial fatty infiltration ratio (SFIR) at C4-C7 in the cervical SCI group were significantly higher than those in the control group (P < 0.001). The cross-sectional area of the functional deep extensor area (FDEA) relative to the vertebral body area (VBA) and the cross-sectional area of the functional superficial extensor area (FSEA) relative to the VBA at the C5 and C6 levels in the cervical SCI group were significantly lower than those in the control group (P < 0.001, P < 0.001, P = 0.034, P = 0.004 respectively). Among the cervical SCI patients, the cross-sectional areas of the deep extensor area (DEA) and the superficial extensor area (SEA) in males were significantly higher than those in females (P < 0.001). At the C6 and C7 levels, the FDEA/VBA and FSEA/VBA ratios in the male group were higher than those in the female group (P = 0.009, P = 0.022, P = 0.019, P = 0.005, respectively). CONCLUSION: Patients with acute cervical SCI exhibit significantly higher fatty infiltration and a greater degree of paravertebral extensor muscle degeneration compared to healthy controls. This finding underscores the importance of the paravertebral extensor muscles in the context of cervical SCI and may guide future therapeutic strategies.

Regulation of KLRC and Ceacam gene expression by miR-141 supports cell proliferation and metastasis in cervical cancer cells.

INTRODUCTION: MicroRNAs (miRNAs) are single RNA molecules that act as global regulators of gene expression in mammalian cells and thus constitute attractive targets in treating cancer. Here we aimed to investigate the possible involvement of miRNA-141 (miR-141) in cervical cancer and to identify its potential targets in cervical cancer cell lines. METHODS: The level of miR-141 in HeLa and C-33A cells has been assessed using the quantitative real-time PCR (qRT-PCR). A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HeLa cells. The protein profile of killer-like receptor C1 (KLRC1), KLRC3, carcinoembryonic antigen-related cell adhesion molecule 3 (CAM3), and CAM6 was investigated in HeLa cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced cytokines from transfected HeLa cells. RESULTS: The expression of miR-141 significantly increased in HeLa and C-33A cells compared to the normal cervical HCK1T cell line. Transfection of HeLa cells with an inhibitor, antagonist miR-141, showed a potent effect on cancer cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HeLa cells overexpressed miR-141 provided a hundred of downregulated genes, including KLRC1, KLRC3, CAM3, and CAM6. KLRC1 and KLRC3 expression profiles markedly depleted in HeLa cells transfected with miR-141 overexpression accompanied by decreasing interleukin 8 (IL-8), indicating the role of miR-141 in avoiding programmed cells death in HeLa cells. Likewise, CAM3 and CAM6 expression reduced markedly in miR-141 transduced cells accompanied by an increasing level of transforming growth factor beta (TGF-ß), indicating the impact of miR-141 in cancer cell migration. The IntaRNA program and miRWalk were used to check the direct interaction and potential binding sites between miR-141 and identified genes. Based on this, the seeding regions of each potential target was cloned upstream of the luciferase reporter gene in the pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HeLa cells pre-transfected with miR-141 overexpression vector, while increasing enormously in cells pre-transfected with miR-141 specific inhibitor. CONCLUSION: Together, these data uncover an efficient miR-141-based mechanism that supports cervical cancer progression and identifies miR-141 as a credible therapeutic target.

Breast cancer and cervical cancer: a comparison of the period before and during the COVID-19 pandemic.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic impacted cancer health care in several countries, with delays in the detection and treatment of breast and cervical cancer. The objective of this study is to analyze and compare the screening, diagnosis and treatment of breast and cervical cancer in the pre-COVID period and during the COVID-19 period. METHODS: Cross-sectional study with secondary data collected from the Mortality Information System (SIM), Hospital Information System (SIH), Ambulatory Information System (SIA) and the Oncology Panel (PO) of breast cancer notifications with ICD C50.0 to C50.9 and cervix ICD C53.0 to C53.9, The analyzed period before the pandemic was from March 1 to October 1, 2019, and during the pandemic from March 1 to October 1, 2020. The period from 2013 to 2022 was also analyzed with the same information, including the number of diagnoses, treatments, and deaths from breast cancer and cervical cancer. The study population consisted of Brazilian women aged 25 to 70 years. In order to compare categorical variables between periods, the Chi-Square or Fisher's Exact tests, and Mann-Whitney U tests were applied, and the Poisson Regression model was applied to model the number of reported cases of COVID-19 and the amount of procedures. RESULTS: There was a decrease in the number of mammograms and cytopathological exams during COVID-19, as well as a decrease in cases of breast and cervical cancer. The Poisson regression showed that the increase in the number of COVID-19 cases caused a decrease in the number of breast cytopathological examinations, cervical-vaginal cytopathological examinations/microflora and screening, diagnosis, initiation of treatment for breast cancer and deaths from this disease. Meanwhile, in some regions of Brazil, as the number of Covid-19 increased, there was a significantly increase in the number of mammograms performed and cervical cancer diagnoses. CONCLUSIONS: The COVID-19 period in 2020 significantly impacted screening, diagnosis, treatment for breast and cervical cancer.

Machine-learning-based prediction by stacking ensemble strategy for surgical outcomes in patients with degenerative cervical myelopathy.

BACKGROUND: Machine learning (ML) is extensively employed for forecasting the outcome of various illnesses. The objective of the study was to develop ML based classifiers using a stacking ensemble strategy to predict the Japanese Orthopedic Association (JOA) recovery rate for patients with degenerative cervical myelopathy (DCM). METHODS: A total of 672 patients with DCM were included in the study and labeled with JOA recovery rate by 1-year follow-up. All data were collected during 2012-2023 and were randomly divided into training and testing (8:2) sub-datasets. A total of 91 initial ML classifiers were developed, and the top 3 initial classifiers with the best performance were further stacked into an ensemble classifier with a supported vector machine (SVM) classifier. The area under the curve (AUC) was the main indicator to assess the prediction performance of all classifiers. The primary predicted outcome was the JOA recovery rate. RESULTS: By applying an ensemble learning strategy (e.g., stacking), the accuracy of the ML classifier improved following combining three widely used ML models (e.g., RFE-SVM, EmbeddingLR-LR, and RFE-AdaBoost). Decision curve analysis showed the merits of the ensemble classifiers, as the curves of the top 3 initial classifiers varied a lot in predicting JOA recovery rate in DCM patients. CONCLUSIONS: The ensemble classifiers successfully predict the JOA recovery rate in DCM patients, which showed a high potential for assisting physicians in managing DCM patients and making full use of medical resources.

External jugular venous aneurysm: A rare case report.

Venous aneurysms of the external jugular vein are rare vascular anomalies due to the low pressure in the venous circulation i.e. the superior vena cava. A review of the literature reveals that external jugular vein aneurysms are reported rarely but the exact incidence of such aneurysms is not known. The presentation of external jugular vein aneurysms can vary widely but generally, they present as a soft cervical mass which gradually increases in size. These aneurysms pose a diagnostic and management challenge for the clinician as their clinical spectrum ranges from being asymptomatic, to cosmetic concerns or they can potentially cause thrombosis, embolism, or thrombophlebitis. Diagnosis is confirmed via Color Doppler ultrasound and computerized tomogram angiography. We present the clinical features and diagnosis of a saccular external jugular vein pseudoaneurysm in a 58-year-old female, which was most likely to be congenital and was diagnosed using computerized tomogram angiography.

Efficacy of PD-1 or PD-L1 inhibitors for the therapy of cervical cancer with varying PD-L1 expression levels: a single-arm meta-analysis.

Objective: To assess the effectiveness and tolerability of both PD-1 and PD-L1 inhibitors in advanced cervical cancer (CC), focusing on varying PD-L1 levels. Methods: A comprehensive exploration was carried out on EMBASE, PubMed, Cochrane Library databases as well as Web of Science up to May 25, 2024, for studies involving advanced CC patients receiving PD-1/PD-L1 inhibitors. Inclusion criteria were studies reporting objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), as well as median overall survival (OS). Data extraction and quality assessment were performed by two reviewers using the JBI Case Series Critical Appraisal Checklist, followed by a meta-analysis via STATA/MP 16.0. Results: Five eligible studies comprising 223 patients were chosen. ORR and DCR were 42% (95% CI: 17%-66%, P = 0.00) and 70% (95% CI: 22%-117%, P = 0.00), respectively, in the PD-L1 positive patients and were 36% (95% CI: 17%-54%, P = 0.00) and 47% (95% CI: 30%-63%, P = 0.00), respectively, in patients with PD-L1 negativity. For patients exhibiting PD-L1 positivity, median PFS and median OS were 3.98 months (95% CI: 0.80-7.16, P = 0.01) and 11.26 months (95% CI: 3.01-12.58, P = 0.00), respectively. Conclusion: With PD-1/PD-L1 inhibitors, PD-L1 positive CC patients demonstrate superior ORR, DCR, median PFS, and median OS, underscoring PD-L1 as one biomarker for immunotherapy response.

Concussion Reduction in Division I and II Athletes: Effects of Simple Cervical Spine Exercise Regimen.

INTRODUCTION:  Primary preventative medicine lacks a consensus on effective concussion prevention strategies for collegiate athletes. Cervical strength has been identified as a potential factor in concussion risk reduction. This study evaluates the impact of a commercially available, portable cervical muscle stretching and strengthening device, NeckX®, on cervical strength, range of motion (ROM), and concussion incidence in collegiate athletes participating in high-concussion-risk sports. METHODS:  A single-arm prospective cohort study was conducted with 162 collegiate athletes from various sports. Participants underwent a 12-week neck exercise protocol using the NeckX® device. Clinical data, including neck strength and ROM, were collected at weeks 0, 6, and 12. Concussion incidence was self-reported by participants and cross-referenced with records from the athletic department. Data were analyzed for significant neck strength and ROM changes throughout the 12-week study. A two-way analysis of variance multiple comparisons with the Tukey-Kramer significant difference test was utilized, using the Holm-Sidak method, with an alpha of 0.05. RESULTS:  All athletic teams experienced a significant increase in cervical strength during the 12-week intervention (α = 0.05, p < 0.05). Increases in cervical flexion and extension force were most consistent between teams. Cervical ROM increased significantly in male and female soccer players (α = 0.05, p < 0.05). The overall incidence of head and neck injuries, including concussions, was reduced to 6.60% during the study period, the lowest recorded value in the university's athletic department history. CONCLUSION:  The use of the NeckX® device for 12 weeks was effective in enhancing pericervical muscle strength and ROM while reducing concussion incidence in collegiate athletes participating in high-concussion-risk sports. Interestingly, the positive outcomes were consistent for both males and females, indicating the universal advantages of neck training among collegiate athletes. These findings support existing research on the benefits of cervical strengthening exercises for reducing concussions in collegiate athletes and highlight the convenience and affordability of using this device.