Cervical cancer prevention in China: where are we now, and what's next?

Cervical cancer(CC) epidemiology CC, the fourth most frequently diagnosed malignancy in women worldwide, is a major global health challenge, particularly in low-resource regions. Approximately 88.1% of the 604,000 CC new cases occurred in low-and middle-income countries in 2020, and more than 90% of the 342,000 CC deaths occurred in low-and middle-income countries in 2020~1.

Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

Promising outcomes 5 weeks after a surgical cervical shunting procedure to unclog cerebral lymphatic systems in a patient with Alzheimer’s disease

Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposits,accelerating the onset and progression of Alzheimer’s disease(AD).12 Given that cervical lymph nodes receive cerebrospinal fluid from the brain’s glymphatic system,34 we speculated that decompression of the lymphatic trunk and cervical lymphatic-venous anastomosis(LVA)could facilitate the flow of cerebrospinal fluid in the cranial glymphatic system,potentially accelerating the clearance of harmful beta-amyloid and tau proteins.We collaborated with surgeons who specialise in LVA supermicrosurgery for maxillofacial tumours and lymphoedema to develop a procedure to relieve the blockage of the glymphatic system.This surgery employs supermicrosurgery techniques to create LVA connecting the bilateral cervical,deep lymphatic vessels to the veins,resulting in lymphatic trunk decompression,which allows the lymph fluid in the high-pressure lymphatic vessels to flow into the low-pressure venous system.The goal of the minimally invasive surgery is to enhance the removal of proteins,such as beta-amyloid and tau,from the brain’s lymphatic systems to the maxillofacial lymphatic vessels,unclogging protein blockages within the brain.This extracranial procedure is safer than intracranial approaches.

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

Combining neural progenitor cell transplant and rehabilitation for enhanced recovery after cervical spinal cord injury

Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control in humans.This system has historically been the most refractory to regenerative efforts after SCI.The "nonregeneration" of the CST changed when robust regeneration of the CST into spared tissue was demonstrated by the inactivation of phosphatase and tensin homolog and delivery of inosine.

Cervical Cancer Prediction Empowered with Federated Machine Learning

Cervical cancer is an intrusive cancer that imitates various women around the world. Cervical cancer ranks in thefourth position because of the leading death cause in its premature stages. The cervix which is the lower end of thevagina that connects the uterus and vagina forms a cancerous tumor very slowly. This pre-mature cancerous tumorin the cervix is deadly if it cannot be detected in the early stages. So, in this delineated study, the proposed approachuses federated machine learning with numerous machine learning solvers for the prediction of cervical cancer totrain the weights with varying neurons empowered fuzzed techniques to align the neurons, Internet of MedicalThings (IoMT) to fetch data and blockchain technology for data privacy and models protection from hazardousattacks. The proposed approach achieves the highest cervical cancer prediction accuracy of 99.26% and a 0.74%misprediction rate. So, the proposed approach shows the best prediction results of cervical cancer in its early stageswith the help of patient clinical records, and all medical professionals will get beneficial diagnosing approachesfrom this study and detect cervical cancer in its early stages which reduce the overall death ratio of women due tocervical cancer.

Evolutionary Safe Padé Approximation Scheme for Dynamical Study of Nonlinear Cervical Human Papilloma Virus Infection Model

This study proposes a structure-preserving evolutionary framework to find a semi-analytical approximate solution for a nonlinear cervical cancer epidemic(CCE)model.The underlying CCE model lacks a closed-form exact solution.Numerical solutions obtained through traditional finite difference schemes do not ensure the preservation of the model’s necessary properties,such as positivity,boundedness,and feasibility.Therefore,the development of structure-preserving semi-analytical approaches is always necessary.This research introduces an intelligently supervised computational paradigm to solve the underlying CCE model’s physical properties by formulating an equivalent unconstrained optimization problem.Singularity-free safe Padérational functions approximate the mathematical shape of state variables,while the model’s physical requirements are treated as problem constraints.The primary model of the governing differential equations is imposed to minimize the error between approximate solutions.An evolutionary algorithm,the Genetic Algorithm with Multi-Parent Crossover(GA-MPC),executes the optimization task.The resulting method is the Evolutionary Safe PadéApproximation(ESPA)scheme.The proof of unconditional convergence of the ESPA scheme on the CCE model is supported by numerical simulations.The performance of the ESPA scheme on the CCE model is thoroughly investigated by considering various orders of non-singular Padéapproximants.

Artificial intelligence strengthens cervical cancer screening–present and future

Cervical cancer is a severe threat to women’s health.The majority of cervical cancer cases occur in developing countries.The WHO has proposed screening 70%of women with high-performance tests between 35 and 45 years of age by 2030 to accelerate the elimination of cervical cancer.Due to an inadequate health infrastructure and organized screening strategy,most low-and middle-income countries are still far from achieving this goal.As part of the efforts to increase performance of cervical cancer screening,it is necessary to investigate the most accurate,efficient,and effective methods and strategies.Artificial intelligence(AI)is rapidly expanding its application in cancer screening and diagnosis and deep learning algorithms have offered human-like interpretation capabilities on various medical images.AI will soon have a more significant role in improving the implementation of cervical cancer screening,management,and follow-up.This review aims to report the state of AI with respect to cervical cancer screening.We discuss the primary AI applications and development of AI technology for image recognition applied to detection of abnormal cytology and cervical neoplastic diseases,as well as the challenges that we anticipate in the future.

Special RCA based sensitive point-of-care detection of HPV mRNA for cervical cancer screening

Developing the sensitive point-of-care testing(POCT)of oncogenic nucleic acids from human papillomavirus(HPV)infection is essential in preventing cervical can-cer,especially in resource-limited settings.Rolling circle amplification(RCA)is attractive in achieving POCT via nucleic acid-based aggregation under isothermal conditions.However,the influence of RCA product structure on the aggregation remains unexplored resulting in limited sensitivity.Here,a minimum secondary structured RCA technique(MSS-RCA)is developed by designing a unique circu-lar template,demonstrating significantly enhanced detection sensitivity with only one amplification step and one primer under isothermal conditions.The amplifi-cation efficiency of MSS-RCA could be kinetically manipulated by controlling the secondary structure of the circular template.Introducing the invertase probe to MSS-RCA,HPV16 E6/E7 nucleic acid target was detected with a personal glucose meter(PGM)with a sensitivity of 5 fM(50 zmol in 10µL).This integrated MSS-RCA-PGM detection system was successfully applied to detect HPV16 E6/E7 mRNA extracted from 54 cervical swab samples reaching a positive predictive value of 100.00%and negative predictive values of 96.00%(77.77%to 99.40%,95%CI).MSS-RCA-PGM provides a sensitive POCT platform for the detection of nucleic acid biomarkers for screening of cervical cancer or other diseases.

Knockdown of circular RNA (CircRNA)_001896 inhibits cervical cancer proliferation and stemness in vivo and in vitro

Objective:Previous studies indicated that aberrant circular RNA(circRNA)expression affects gene expression regulatory networks,leading to the aberrant activation of tumor pathways and promoting tumor cell growth.However,the expression,clinical significance,and effects on cell propagation,invasion,and dissemination of circRNA_001896 in cervical cancer(CC)tissues remain unclear.Methods:The Gene Expression Omnibus(GEO)datasets(GSE113696 and GSE102686)were used to examine differential circRNA expression in CC and adjacent tissues.The expression of circRNA_001896 was detected in 72 CC patients usingfluorescence quantitative PCR.Correlation analysis with clinical pathological features was performed through COX multivariate and univariate analysis.The effect of circRNA_001896 downregulation on CC cell propagation was examined using the cell counting kit-8(CCK-8)test,clonogenic,3D sphere formation,and in vivo tumorigenesis assays.Results:Intersection of the GSE113696 and GSE102686 datasets revealed an increased expression of four circRNAs,including circRNA_001896,in CC tissues.Fluorescence quantitative PCR confirmed circRNA_001896 as a circular RNA.High expression of circRNA_001896 was considerably associated with lymph node metastasis,International Federation of Gynecologists and Obstetricians(FIGO)stage,tumor diameter,and survival period in CC patients.Proportional hazards model(COX)univariate and multivariate analyses revealed that circRNA_001896 expressions are a distinct risk factor affecting CC patients’prognosis.Cellular functional experiments showed that downregulating circRNA_001896 substantially suppressed CC cell growth,colony formation,and 3D sphere-forming ability.In vivo,tumorigenesis analysis in nude mice demonstrated that downregulating circRNA_001896 remarkably reduced the in vivo proliferation capacity of CC cells.Conclusion:CircRNA_001896 is highly expressed in CC tissues and is substantially related to lymph node metastasis,FIGO stage,tumor size,and survival period in patients.Moreover,downregulating circRNA_001896 significantly inhibits both in vivo and in vitro propagation of CC cells.Therefore,circRNA_001896 might be used as a biomarker for targeted therapy in cervical cancer.

LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis

At present,the role of many long non-coding RNAs(lncRNAs)as tumor suppressors in the formation and development of cervical cancer(CC)has been studied.However,lncRNA prostate cancer gene expression marker 1(PCGEM1),whose high expression not only aggravates ovarian cancer but also can induce tumorigenesis and endometrial cancer progression,has not been studied in CC.The objective of this study was to investigate the expression and the underlying role of PCGEM1 in CC.The relative expression of PCGEM1 in CC cells was detected by real-time PCR.After the suppression of PCGEM1 expression by shRNA,the changes in the proliferation,migration,and invasion capacities were detected via CCK-8 assay,EdU assay,and colony formation assay wound healing assay.Transwell assay and the changes in expressions of epithelial-to-mesenchymal transition(EMT)markers were determined by western blot and immunofluorescence.The interplay among PCGEM1,miR-642a-5p,and kinesin family member 5B(KIF5B)was confirmed by bioinformatics analyses and luciferase reporter assay.Results showed that PCGEM1 expressions were up-regulated within CC cells.Cell viabilities,migration,and invasion were remarkably reduced after the suppression of PCGEM1 expression by shRNA in Hela and SiHa cells.N-cadherin was silenced,but E-cadherin expression was elevated by sh-PCGEM1.Moreover,by sponging miR-642a-5p in CC,PCGEM1 was verified as a competitive endogenous RNA(ceRNA)that modulates KIF5B levels.MiR-642a-5p down-regulation partially rescued sh-PCGEM1’s inhibitory effects on cell proliferation,migration,invasion,and EMT process.In conclusion,the PCGEM1/miR-642a-5p/KIF5B signaling axis might be a novel therapeutic target in CC.This study provides a research basis and new direction for targeted therapy of CC.

Acupuncture for cervical dystonia associated with anxiety and depression: A case report

BACKGROUND Cervical dystonia(CD)is a type of muscle tone disorder that usually occurs in the neck muscles.Due to the intermittent or continuous involuntary contraction of the neck muscles,the head and neck are twisted and skewed and some postural abnormalities occur.Long-term abnormal posture or pain can cause negative emotions in patients,which can affect their quality of life.CASE SUMMARY This case report included a 37-year-old woman who was diagnosed with CD associated with anxiety and depression;the accompanying symptoms were head and neck tilt of approximately 90°to the right and mental abnormality.After two courses of acupuncture treatment,the patient’s head and neck can be maintained in a normal position,and the negative emotions can be relieved.CONCLUSION This case indicates that acupuncture can effectively improve CD and the emotional state and quality of life of patients,making it an effective alternative treatment for the condition.

Retraction:miR-181a-5p Promotes Proliferation and Invasion and Inhibits Apoptosis of Cervical Cancer Cells via Regulating Inositol Polyphosphate-5-Phosphatase A(INPP5A)

Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.

Can we triumph over locally advanced cervical cancer with colossal para-aortic lymph nodes? A case report

BACKGROUND Para-aortic lymph nodes(PALNs)are common sites for the regional spread of cervical squamous cell carcinoma(SCC).CASE SUMMARY We report the case of a 36-year-old woman who presented with cervical SCC with multiple bulky PALNs,largest measured 4.5 cm×5 cm×10 cm.The patient was treated with radical intent with definitive chemoradiation using sequential doseescalated adaptive radiotherapy,followed by maintenance chemotherapy.The patient achieved a complete response;she has been doing well since the completion of treatment with no evidence of the disease for 2 years.CONCLUSION Regardless of the size of PALN metastases of cervical carcinoma origin,it is still treatable(with radical intent)via concurrent chemoradiation.Adaptive radiotherapy allows dose escalation with minimal toxicity.

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis,prognosis and recurrence risk in patients with cervical epithelioma

BACKGROUND Cervical intraepithelial neoplasia(CIN)is an important precursor of cervical cancer.Early detection and treatment can reduce the incidence of cervical cancer.AIM To investigate the detection rate of human papillomavirus(HPV)E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia(CIN)and its relationship with CIN progression and diagnosis.METHODS One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected.These patients were graded CIN based on colposcopy and cervical pathology.The positive expression rates of HPV E6/E7 mRNA and HPV[polymerase chain reaction(PCR)-reverse dot crossing]were compared among all groups.Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr.The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis.RESULTS The diagnostic sensitivity,specificity,and sensitivity of PCR-reverse point hybrid ization technology for secondary CIN were 70.41%,70.66%,and 0.714,respectively.Sensitivity and specificity for secondary CIN were 752%and 7853%,respectively,the area under the curve value was 0.789.Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I(P<0.05).In CIN grade I patients with positive for HPV E6/E7 mRNA,in its orientation to grade CIN patients,in its orientation to grade CIN patients,at 69.2%,compared with patients negative for HPV E6/E7 mRNA(30.8%),significant difference(P<0.05).CONCLUSION HPV E6/E7 mRNA and HPV(PCR-reverse dot hybrid)positive expression have a close relationship with CINgrade disease progression and is an independent risk factor for high-grade CIN lesions.

Hounsfield units in assessing bone mineral density in ankylosing spondylitis patients with cervical fracture-dislocation

BACKGROUND Cervical spine fracture-dislocations in patients with ankylosing spondylitis(AS)are mostly unstable and require surgery.However,osteoporosis,one of the comorbidities for AS,could lead to detrimental prognoses.There are few accurate assessments of bone mineral density in AS patients.AIM To analyze Hounsfield units(HUs)for assessing bone mineral density in AS patients with cervical fracture-dislocation.METHODS The HUs from C2 to C7 of 51 patients obtained from computed tomography(CT)scans and three-dimensional reconstruction of the cervical spine were independently assessed by two trained spinal surgeons and statistically analyzed.Inter-reader reliability and agreement were assessed by interclass correlation coefficient.RESULTS The HUs decreased gradually from C2 to C7.The mean values of the left and right levels were significantly higher than those in the middle.Among the 51 patients,25 patients(49.02%)may be diagnosed with osteoporosis,and 16 patients(31.37%)may be diagnosed with osteopenia.CONCLUSION The HUs obtained by cervical spine CT are feasible for assessing bone mineral density with excellent agreement in AS patients with cervical fracture-dislocation.

Potential of non-Western medicines in chemoradiotherapy for cervical cancer

This editorial explores the potential integration of non-Western medicine into radiotherapy for cervical cancer.While radiotherapy remains a radical treatment for cervical cancer,its associated toxicity and decline in quality of life can significantly impact patients’lives.Currently,most treatments are supportive,with no specific treatment options available in Western medicine.Non-Western medicine,often less toxic and easier to administer,has shown promising results when used alongside radiotherapy for cervical cancer.Despite these potential benefits,challenges such as limited evidence and restricted application areas persist.While non-Western medicines may offer potential improvements in chemoradiotherapy outcomes for cervical cancer,further research is necessary to substantiate these benefits.

Steel bar penetrating cervical spinal canal without neurological injury:A case report

BACKGROUND We report a rare case of cervical spinal canal penetrating trauma and review the relevant literatures.CASE SUMMARY A 58-year-old male patient was admitted to the emergency department with a steel bar penetrating the neck,without signs of neurological deficit.Computed tomography(CT)demonstrated that the steel bar had penetrated the cervical spinal canal at the C6–7 level,causing C6 and C7 vertebral body fracture,C6 left lamina fracture,left facet joint fracture,and penetration of the cervical spinal cord.The steel bar was successfully removed through an open surgical procedure by a multidisciplinary team.During the surgery,we found that the cervical vertebra,cervical spinal canal and cervical spinal cord were all severely injured.Postoperative CT demonstrated severe penetration of the cervical spinal canal but the patient returned to a fully functional level without any neurological deficits.CONCLUSION Even with a serious cervical spinal canal penetrating trauma,the patient could resume normal work and life after appropriate treatment.

Mycobacterium gordoniasis of the cervical lymph nodes:A case report

BACKGROUND Owing to the advancement in bacterial identification techniques,the detection rate of non-tuberculous mycobacterium(NTM)has been on the rise.Different from Mycobacterium tuberculosis,the clinical symptoms of NTM are not easily detected,and the clinical efficacy and prognosis are somewhat heterogeneous.To report a case of Mycobacterium gordoniasis of cervical lymph node diagnosed in Anhui Chest Hospital in July 2022.CASE SUMMARY Upon examination,the patient who weighed 67.5 kg,was human immunodeficiency virus negative,healthy,without hypertension,diabetes,heart disease and other basic diseases microscopic analysis revealed granulomatous inflammation with coagulation necrosis in the lymphocyte,and tuberculosis was not ruled out.Plain computed tomography scans of the neck and chest indicated the presence of a single grayish-yellow and grayish-brown tissue,the dimensions of which was top of form 10.5 cm×3.0 cm×1.5 cm.After pathological consultation in our hospital,the diagnosis was confirmed as NTM infection.CONCLUSION This case report and the clinical epidemiological research on improving NTM have important guiding significance for improving decision-making in clinical treatments.