Distant organ metastasis patterns and prognosis of cervical adenocarcinoma: a population-based retrospective study.

Background: Adenocarcinoma is a common histological subtype of cervical cancer, accounting for 10-15% of all cases. The prognosis of cervical adenocarcinoma with distant organ metastases remains unclear. Therefore, our study aimed to investigate the patterns and prognosis of distant organ metastasis in cervical adenocarcinoma. Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2019. Cox regression, Kaplan-Meier, and log-rank analyses were conducted. Results: We observed that adenocarcinoma (AC) of the cervix primarily metastasizes to single organs, with a rate of 73.3%. The lungs are the most common organs of metastasis, followed by the liver and bones. Patients with bone metastases have a median survival period of 12 months, which is slightly longer compared to metastasis in other organs. Distant organ metastasis, age, positive lymph nodes, higher AJCC stages, larger tumor diameter, and higher cell grades are related to poor prognosis (p < 0.001). Furthermore, we have observed that surgical intervention, radiotherapy, and chemotherapy can potentially provide benefits for patients with distant organ metastases. Conclusion: Metastasis is an independent prognostic factor for cervical adenocarcinoma patients. Surgery, radiotherapy, and chemotherapy can provide an overall survival advantage for patients with distant organ metastases.

Decoding Fujian's cervical HPV landscape: unmasking dominance of non-16/18 HR-HPV and tailoring prevention strategies at a large scale.

Background: Persistent HR-HPV causes cervical cancer, exhibiting geographic variance. Europe/Americas have higher HPV16/18 rates, while Asia/Africa predominantly have non-16/18 HR-HPV. This study in Fujian, Asia, explores non-16/18 HR-HPV infections, assessing their epidemiology and cervical lesion association for targeted prevention. Methods: A total of 101,621 women undergoing HPV screening at a hospital in Fujian Province from 2013 to 2019 were included. HPV genotyping was performed. A subset of 11,666 HPV-positive women with available histopathology results were analyzed to characterize HPV genotype distribution across cervical diagnoses. Results: In 101,621 samples, 24.5% tested positive for HPV. Among these samples, 17.3% exhibited single infections, while 7.2% showed evidence of multiple infections. The predominant non-16/18 high-risk HPV types identified were HPV 52, 58, 53, 51, and 81. Single HPV infections accounted for 64.1% of all HPV-positive cases, with 71.4% of these being non-16/18 high-risk HPV infections. Age-related variations were observed in 11,666 HPV-positive patients with pathological results. Cancer patients were older. In the cancer group, HPV52 (21.8%) and HPV58 (18.6%) were the predominant types, followed by HPV33, HPV31, and HPV53. Compared to single HPV16/18 infection, non-16/18 HPV predominated in LSIL. Adjusted odds ratios (OR) for LSIL were elevated: multiple HPV16/18 (OR 2.18), multiple non-16/18 HR-HPV (OR 2.53), and multiple LR-HPV (OR 2.38). Notably, solitary HPV16/18 conferred higher odds for HSIL and cancer. Conclusion: Our large-scale analysis in Fujian Province highlights HPV 52, 58, 53, 51, and 81 as predominant non-16/18 HR-HPV types. Multiple HPV poses increased LSIL risks, while solitary HPV16/18 elevates HSIL and cancer odds. These findings stress tailored cervical cancer prevention, highlighting specific HPV impacts on lesion severity and guiding region-specific strategies for optimal screening in Asia, emphasizing ongoing surveillance in the vaccination era.

Clinical Characteristics and Detection Sensitivity of Cervical Cancer Screening in Vaginal Intraepithelial Neoplasia.

OBJECTIVE: This study aimed to investigate the characteristics and screening history of vaginal intraepithelial neoplasia (VaIN) or vaginal cancer and compare the sensitivity of cytology and human papillomavirus (HPV) tests on the cervix against vaginal and cervical high-grade squamous intraepithelial lesion or cancer. METHODS: This study included patients who underwent colposcopy-directed biopsy and were diagnosed with VaIN or vaginal cancer from February 2013 to November 2022. Clinical information was obtained from the medical records of the department. Statistical analysis was performed on SPSS 26.0 (IBM Corp, Armonk, NY) using t test, chi-square, and Fisher exact tests. RESULTS: A total of 1,166 patients were included in this study. The median age of VaIN2+ patients was 50.5 years, whereas VaIN1 reported a median age of 42.1 years old, p < .001. This study reported that VaIN was significantly and positively correlated with cervical lesions (r = 0.244). The high-risk HPV (hr-HPV) detection rate was 88.2% (858/973) in VaIN and 95.2% in VaIN2+. Human papillomavirus 16 was the most prevalent HPV type in VaIN2+, which accounted for 54.9%, followed by HPV58 (19.5%), HPV52 (15.2%), HPV51 (12.2%), and HPV18 (11.0%). The sensitivity of hr-HPV and cytology tests on the cervix for detecting VaIN2+ was 94.7% and 83.4%, respectively. Both tests were not significantly different from detecting cervical intraepithelial neoplasia 2+. CONCLUSIONS: Human papillomavirus 16 is the dominant HPV type in vaginal precancer lesions. Cervical cancer screening has similar sensitivity for VaIN2+ as for cervical intraepithelial neoplasia 2+, with hr-HPV testing showing higher sensitivity than cytology.

Associations of multi-human papillomavirus infections with expression of p16 in a cohort of women who underwent colposcopy: a retrospective study of 5165 patients.

Objective: Investigate HPV types in cervical specimens, their correlation with p16 expression in lesions, and diagnostic value for cervical lesions. Enhance clinical diagnosis reliability. Methods: Retrospective cross-sectional study at Fujian Maternity and Child Health Hospital's Cervical Disease Center (Jun 2019-Dec 2021). Patients with abnormal cervical screening underwent colposcopy and conization. Pathological diagnosis based on colposcopy, cervical biopsy, ECC, and conization. Analyzed HPV genotyping (18 HR-HPV, 5 LR-HPV) and p16 expression correlation. Statistical analysis used R software. Results: he expression of p16 is significantly associated with the infection of high-risk HPV types, such as 16, 33, 52, and 58, with an increased risk of 1.4 times or higher (OR=1.91, 3.14, 1.40, and 1.78, respectively). The risk of p16 expression increased 4-fold for multiple high-risk HPV types [adjusted OR (95% CI) = 4 (2.92~5.5), P-value <0.001]. Compared to the p16(-) group, the p16(+) group had a higher association with cervical lesions worse than HSIL (High-grade Squamous Intraepithelial Lesions).In the group with multiple Human Papillomavirus Infections with types 16, 33, 52, and 58, the risk of cervical lesions worse than HSIL increased by up to 660-fold compared to the negative group (adjusted OR=660.62, 95% CI: 91.39~4775.53, P<0.001), indicating that this combination of HPV types posed the greatest risk for cervical lesions above HSIL. Conclusions: p16 plays a crucial role in cervical lesion progression, linked to high-risk HPV. Combining p16 with HPV screening improves cervical cancer detection. Studying multiple HPV infections will enhance prevention and management.

Exosomal miR-99b-5p Secreted from Mesenchymal Stem Cells Can Retard the Progression of Colorectal Cancer by Targeting FGFR3.

Human bone marrow mesenchymal stem cells (BMSCs) are efficient mass producers of exosomes that can potentially be utilized for delivery of miRNAs in cancer therapy. The current study aimed to assess the role of MSC-exosomal miR-99b-5p during the development of colorectal cancer (CRC). The potential value of using plasma levels of exosomal miR-99b-5p for predicting the liver metastasis of colorectal cancer was also assessed. In this study, we found that overexpression of fibroblast growth factor receptor 3 (FGFR3) was associated with tumor progression in CRC and FGFR3 was the target gene of miR-99b-5p, which was down-regulated in CRC tissues. Furthermore, we observed that elevated miR-99b-5p inhibited CRC cell proliferation, invasion and migration, while reduced levels had the opposite effect on CRC cells. Moreover, exosomal miR-99b-5p delivered by BMSCs was able to limit the proliferation, invasion and migration of CRC cells in vitro, as well as suppressing tumor growth in vivo. Collectively, these findings revealed that MSC-derived exosomal miR-99b-5p can be transferred into CRC cells and which can suppress tumor progression by targeting FGFR3. This highlights the potential of using exosomal miR-99b-5p as a novel diagnostic marker for CRC, while providing a therapeutic target to combat CRC.

Can inspiratory muscle training benefit patients with COVID-19? A systematic review and meta-analysis.

The possible benefits of inspiratory muscle training (IMT) on mechanical and clinical outcomes in patients with Coronavirus disease-2019 (COVID-19) remain controversial. We conducted a meta-analysis to evaluate the effect of IMT in the rehabilitation strategy of patients with COVID-19. The Pubmed, Embase, Web of Science (WOS), and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify trials evaluating the efficacy of IMT in the treatment of patients with COVID-19. The primary outcome included change from baseline of VO2 max, maximal inspiratory pressure (PImax), 6-min walk test(6MWT), forced expiratory volume in the first second predicted (FEV1%pred), and quality of life (QOL). Six studies with 349 participants were analyzed. Significant improvements were found in change from baseline of VO2 max (MD: 4.54, 95% confidence interval [CI]: 1.79-7.30, Z = 3. 32, I2 = 0, p = 0.001), PImax (MD: 21.43, 95% CI: 1.33-41.52, Z = 2.09, I2 = 90%, p = 0.04), 6MWD (MD: 40.13, 95% CI: 24.92-55.35, Z = 5.17, I2 = 0, p < 0.00001) and FEV1%pred (MD: 8.73, 95% CI 3.07-14.39, Z = 3.02, p = 0.002) while no statistical improvements were found in QOL (SMD: 0.70, 95% CI: 0.37-1.03, Z = 4.15, I2 = 89% p = 0.32) between IMT group and control group. The application of IMT might elicit mechanical and clinical improvement in patients with COVID-19. IMT could be recommended as an effective strategy of pulmonary rehabilitation for COVID-19. However, the proper timing, optimal duration, as well as appropriate frequency and intensity of IMT remain uncertain and further studies are needed.

Associations of human papillomavirus genotypes and cervical vascular abnormality in a cohort of women underwent colposcopy, a retrospective study of 6716 patients.

Aims: Abnormal vessel patterns are specific signs in patients with early cervical abnormality and cervical cancer(CC) by colposcopy, but the impact of human papillomavirus (HPV) infections on abnormal vessel patterns remains unknown. Methods: A total of 6716 female patients with HPV infections or cytological abnormalities who underwent a colposcopy following abnormal CC screening results were included in the study. The final pathological diagnosis was confirmed to be the most severe pathological grade across cervical biopsy, endocervical canal curettage (ECC) and conization. Univariate and multivariate logistic regression analyses were used to investigate the association between HPV infections and abnormal vessel patterns, adjusting for age, gravidity and parity. Results: There were 6124 normal vascular cases by colposcopy and 592 cases with cervical vascular abnormality. The prevalence of HPV infections was 4284 (70%) in normal patients, and the prevalence of HPV infections was 479 (80%) in cervical vascular abnormality patients. HPV high-risk type 16 infection alone increased the risk of cervical heteromorphic blood vessels (aOR=3.66, 95%CI: 2.54~5.27). HPV 16 and 33 alone (other than the commonly recognized subtype of 18) or coinfection of these two genotypes could increase the risk of cervical punctate vascular and cervical vascular mosaic features and abnormal cervical blood vessels. An increased risk of abnormal cervical lesions was observed for HPV 16 and 33 alone or combined in coinfection compared to the negative group. The risk of cervical vascular abnormality was increased 10-fold by coinfection with HPV 16 and 33 (aOR=10.67, 95% CI: 4.54~25.09, P<0.001). HPV 16, 33 alone or combined in coinfection were associated with an increased risk of lesions more advanced than high-grade squamous intraepithelial lesion (HSIL) when compared to the negative group. The risk of lesions more advanced than HSIL was up to 26-fold higher in the coinfection with HPV 16 and 33 group than in the negative group (aOR=26.23, 95%CI: 11.23~61.27, P<0.001). Conclusion: HPV16 and 33 are the most dangerous HPV genotypes correlated with abnormal vascular patterns. Combined HPV16 and HPV33 infection increases the risk of abnormal vascular patterns. Combined HPV16 and HPV33 infection increases the risk of developing HSIL+.

Prognostic nomograms integrating preoperative serum lipid derivative and systemic inflammatory marker of patients with non-metastatic colorectal cancer undergoing curative resection.

Background: Lipid metabolism and cancer-related inflammation are closely related to the progression and prognosis of colorectal cancer (CRC). Therefore, this study aims to establish novel nomograms based on the combined detection of preoperative blood lipids and systemic inflammatory indicators to predict the overall survival (OS) and cancer-specific survival (CCS) of CRC patients. Methods: A total of 523 patients with stage I-III CRC in our institute were collected from 2014 to 2018. The independent predictors for OS and CCS were determined by forward stepwise Cox regression for the establishment of prognostic models. The superiorities of different models were compared by concordance index (C-index), Akaike information criterion (AIC) and integrated discrimination improvement analysis. The performance of the nomograms based on the optimal models was measured by the plotting time-dependent receiver operating characteristic curves, calibration curves, and decision curves, and compared with the tumor-node-metastasis (TNM) staging system. The cohort was categorized into low-risk, medium-risk and high-risk groups according to the risk points of the nomogram, and analyzed using Kaplan-Meier curves and log-rank test. Results: Preoperative TG/HDL-C ratio (THR) ≥ 1.93 and prognostic nutritional index (PNI) ≥ 42.55 were independently associated with favorable outcomes in CRC patients. Six (pT stage, pN stage, histological subtype, perineural invasion, THR and PNI) and seven (pT stage, pN stage, histological subtype, perineural invasion, gross appearance, THR and PNI) variables were chosen to develop the optimal models and construct nomograms for the prediction of OS and CCS. The models had lower AIC and larger C-indexes than other models lacking either or both of THR and PNI, and improved those integrated discrimination ability significantly. The nomograms showed better discrimination ability, calibration ability and clinical effectiveness than TNM system in predicting OS and CCS, and these results were reproducible in the validation cohort. The three risk stratifications based on the nomograms presented significant discrepancies in prognosis. Conclusion: Preoperative THR and PNI have distinct prognostic value in stage I-III CRC patients. The nomograms incorporated the two indexes provide an intuitive and reliable approach for predicting the prognosis and optimizing individualized therapy of non-metastatic CRC patients, which may be a complement to the TNM staging system.

Enterokinase deficiency with novel TMPRSS15 gene mutation masquerading as acrodermatitis enteropathica.

Enterokinase deficiency (EKD) is a rare autosomal recessive inherited disorder caused by loss-of-function mutations of the transmembrane protease serine 15 (TMPRSS15) gene. To date, only 12 cases of EKD have been described in the literature and skin involvement has seldom been described. We identified a novel homozygous nonsense mutation in the TMPRSS15 gene (c.1216C>T, p.R406*) in a female infant, who manifested with acrodermatitis enteropathica (AE)-like lesions that were dramatically relieved within 11 days after initiation of a protein-rich hydrolyzed formula. Our case shows that AE-like rashes can be a manifestation of EKD and expands the spectrum of causative mutations in the TMPRSS15 gene.

A Prognostic Nomogram for Predicting Overall Survival in Patients With Small-Cell Carcinoma of the Uterine Cervix: A SEER Population-Based Study.

Background: This study aimed to develop a prognostic model based on the Surveillance, Epidemiology, and End Results (SEER) database to predict the overall survival (OS) of small cell carcinoma of the uterine cervix (SmCC). Methods: Between 1975 and 2016, a total of 401 patients were included, and their comprehensive sociodemographic and clinicopathological characteristics were collected. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors. The identified factors were used to conduct a nomogram for predicting the OS of SmCC. The performance of the nomogram was determined using area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) metrics. Results: The median survival time of all patients was about 24 months (95% confidence interval [95% CI] [1.50-2.17]). Age (hazard ratio [HR] = 1.693 for 45-59 vs 21-34, 95% CI [1.140-2.513], P = .009; HR = 2.836 for 60-92 vs 21-34, 95% CI [1.851-4.345], P < .001), positive nodes (HR = 2.384, 95% CI [1.437-3.955], P < .001), regional nodes number ≥12 (HR = 0.500, 95% CI [0.282-0.886], P = .018), and treatment method (HR = 0.409 for surgery vs no, 95% CI [0.267-0.628], P < .001; HR = 0.649 for chemotherapy vs no, 95% CI [0.478-0.881)], P = .006) were independent factors of OS. Young patients who had surgical resection or chemotherapy, negative lymph nodes, and regional lymph nodes ≥12 had a longer survival time. These clinical factors were utilized to construct a nomogram for predicting OS. The AUC and C-index were higher than 0.7, indicating the good discriminating ability of the nomogram. The calibrations were all around the 45-degree line, indicating excellent consistency between the prediction of the model and actual observations. The DCA plots supported the clinical utility of the nomogram. Conclusion: The constructed nomogram is expected to help predict the prognosis of SmCC and guide patient treatment.

Prevalence of multiple human papillomavirus infections and association with cervical lesions among outpatients in Fujian, China: A cross-sectional study.

Multiple human papillomavirus (HPV) infections are common, but their impact on cervical lesions remains controversial. A total of 6225 female patients who underwent colposcopies/conization following abnormal cervical cancer screening results were included in the study. The final pathological diagnosis was determined by the most severe pathological grade among the cervical biopsy, endocervical curettage, and conization. Univariate and multivariate logistic regression analyses were used to investigate the association between multiple HPV infections and cervical lesions, adjusting for age, HPV genotype, gravidity and parity. In total, 33.3% (n = 2076) of the study population was infected with multiple HPV genotypes. Multiple HPV infections were more prevalent in patients younger than 25 years and older than 55 years, with the rate of multiple HPV infections at 52.8% and 44.3%, respectively. HPV16\52\18\58 are the most common HPV genotypes and usually appear as a single infection. Compared to single HR-HPV infection, multiple HR-HPV infections do not increase the risk of HSIL+, while single HR-HPV coinfected with LR-HPV seems to reduce the risk of HSIL+ (odds ratio = 0.515, confidence interval: 0.370-0.719, p < 0.001). Multiple HR-HPV infections cannot be risk-stratified for triage of HR-HPV-positive women.

Secondary acrodermatitis enteropathica-like skin findings in a case of methylmalonic acidemia.

Methylmalonic acidemia (MMA) is an autosomal recessive genetic disorder caused by decreased activity of methylmalonyl-CoA mutase or metabolic disturbance of its coenzyme cobalamin, cutaneous manifestations are rare clinical signs in this disease. Herein, we describe a Chinese boy with MMA fed with a formula lacking branched-chain amino acids presenting with erythroderma and acrodermatitis enteropathica-like rash, a homozygous nonsense mutation c.742C>T (p.Gln248*) was identified in the MMAA gene. The pedigree exhibited a non-Mendelian inheritance pattern which was attributed to maternal uniparental disomy on chromosome 4q26-q34.1 of the proband, confirmed by chromosomal microarray analysis. Our case highlights the association between skin changes and nutritional deficiency due to therapeutic amino acid restrictions in MMA.

Clinical and dermoscopic characteristics of onychophagia and onychotillomania: a retrospective study of 63 cases.

Onychophagia and onychotillomania are common forms of nail-biting and nail-picking disorders, but there is insufficient literature documenting their comparison and coexistence. In fact, overlapping features can be involved in different nail self-injuries, and significant variations also exist. We conducted a retrospective study aimed at identifying differences between onychophagia and onychotillomania, and providing more detailed findings of both conditions.

Mesenchymal Stem Cells in Radiation-Induced Pulmonary Fibrosis: Future Prospects.

Radiation-induced pulmonary fibrosis (RIPF) is a general and fatal side effect of radiotherapy, while the pathogenesis has not been entirely understood yet. By now, there is still no effective clinical intervention available for treatment of RIPF. Recent studies revealed mesenchymal stromal cells (MSCs) as a promising therapy treatment due to their homing and differentiation ability, paracrine effects, immunomodulatory effects, and MSCs-derived exosomes. Nevertheless, problems and challenges in applying MSCs still need to be taken seriously. Herein, we reviewed the mechanisms and challenges in the applications of MSCs in treating RIPF.