HPV positivity status in males is related to the acquisition of HPV infection in females in heterosexual couples.

PURPOSE: Few studies have focused on the impact of human papillomavirus (HPV) positivity in male partners on female HPV infection and cervical lesions. The purpose of this study was to evaluate the impact of the HPV infection status of husbands on wives' cervical HPV infection and lesions. METHODS: We surveyed 251 monogamous couples who attended the outpatient department of Fujian Maternity and Child Health Hospital from 2013 to 2021. HPV type analysis was performed on exfoliated cells of the females' cervix and males' urethra by the PCR-reverse dot blot method. We analyzed the prevalence and consistency of HPV types in 251 couples. Subsequently, the risk of HPV infection in females with HPV-positive male partners was analyzed. SPSS version 26 (IBM, Chicago, USA) was used for statistical analysis. RESULTS: In 251 couples, the most commonly detected high-risk HPV (HR-HPV) genotypes were 52, 51, 16, and 58 for males and 16, 52, 18, and 58 for females. Wives with HPV-positive husbands had higher infection rates for most HR-HPV genotypes. HR-HPV positivity in husbands was a risk factor for the development of cervical lesions in wives (OR = 2.250, P = 0.014). Both single-type (OR = 2.085, P = 0.040) and multiple-type (OR = 2.751, P = 0.036) infection in husbands will contributed to an increased risk of non-HR-HPV infection and cervical lesions in wives. CONCLUSION: Husbands' HPV positivity increases the burden of non-HR-HPV infection and increases the risk of cervical lesions developing in wives. It is hoped to provide a reference value for cervical cancer prevention in females and HPV vaccination in males.

Recently urodynamic and quality of life assessment in the non-menopausal women with cervical cancer after radical hysterectomy.

PURPOSE: The aim of this study was to evaluate the pre- and postoperative changes in the recently urodynamic and quality of life (QoL) in nonmenopausal women diagnosed with cervical cancer and treated with radical hysterectomy (RH). PATIENTS AND METHODS: Twenty-eight nonmenopausal women (28-49 years) with cervical carcinoma (FIGO stage Ia2-IIa) underwent a radical hysterectomy. Urodynamic studies were performed 1 week before (U0) and 3-6 months (U1) after surgery. A self-administered condition-specific QoL questionnaire (PFDI-20, PFIQ-7) was applied at U0 and U1. RESULTS: Data from the urodynamics analysis performed at U1 showed that the average first sensation volume (119.39 ± 12.28 ml vs 150.43 ± 31.45 ml, P < 0.001), the residual urine volume (6.39 ± 10.44 ml vs. 42.32 ± 33.72 ml, P < 0.001), and the time of urination (46.10 ± 16.65 s vs. 74.31 ± 23.94 s, P < 0.001) were increased, while the bladder volume at a strong desire to void (448.89 ± 86.62 ml vs. 322.82 ± 50.89 ml, P < 0.001), the bladder compliance (82.63 ± 58.06 ml/cmH2O vs. 37.45 ± 28.66 ml/cmH2O, P < 0.001), the average flow rate (Qave) (23.86 ± 4.25 ml/s vs. 12.57 ± 2.37 ml/s, P < 0.001), the maximum natural flow rate (Qmax) (25.42 ± 6.46 ml/s vs. 14.43 ± 5.32 ml/s, P < 0.001), and the pressure at a peak flow rate (PdetQmax) (36.53 ± 11.20 cmH2O vs. 31.43 ± 10.56 cmH2O, P < 0.05) were decreased. At the same time, functional pelvic problems derived from prolapse (PFDI-20 scores) and their impact on the patients' Qol (PFIQ-7 score) were significantly improved at 3-6 months postoperation. CONCLUSION: Radical hysterectomy results in urodynamic changes, and 3-6 months postoperation may be an important period for changes in bladder dysfunction after RH. Urodynamic and QoL analyses may provide methods for assessing symptoms.

Molecular engineering to red-shift the absorption band of AIE photosensitizers and improve their ROS generation ability.

Photodynamic therapy (PDT) with aggregation-induced emission photosensitizers (AIE-PSs) has attracted increasing attention for their enhanced fluorescence and reactive oxygen species (ROS) generation abilities upon aggregation. However, it is difficult for AIE-PSs to simultaneously achieve long-wavelength excitation (>600 nm) and high singlet oxygen quantum yield, which restricts their application in deep-tissue PDT. In this study, four novel AIE-PSs were developed by appropriate molecular engineering, and their absorption peaks shifted from 478 to 540 nm with a tail extending to 700 nm. Meanwhile, their emission peaks were also moved from 697 nm to 779 nm with a tail extending over 950 nm. Importantly, their singlet oxygen quantum yields successfully increased from 0.61 to 0.89. Moreover, TBQ, the best photosensitizer developed by us, has been successfully applied to image-guided PDT in BALB/C mice bearing 4T1 breast cancer under red light (605 ± 5 nm) irradiation, with IC50 less than 2.5 µM at a low light dose (10.8 J cm-2). The success of this molecular engineering indicates that increasing the number of acceptors is more effective at red-shifting the absorption band of AIE-PSs than increasing the number of donors, and extending the π-conjugation of acceptors will red-shift the absorption-emission band, increase the maximum molar extinction coefficient, and improve the ROS generation ability of AIE-PSs, thus providing a new strategy for the design of advanced AIE-PSs for deep-tissue PDT.

ERRα Up-Regulates Invadopodia Formation by Targeting HMGCS1 to Promote Endometrial Cancer Invasion and Metastasis.

Estrogen-related receptor alpha (ERRα) plays an important role in endometrial cancer (EC) progression. However, the biological roles of ERRα in EC invasion and metastasis are not clear. This study aimed to investigate the role of ERRα and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) in regulating intracellular cholesterol metabolism to promote EC progression. ERRα and HMGCS1 interactions were detected by co-immunoprecipitation, and the effects of ERRα/HMGCS1 on the metastasis of EC were investigated by wound-healing and transwell chamber invasion assays. Cellular cholesterol content was measured to verify the relationship between ERRα and cellular cholesterol metabolism. Additionally, immunohistochemistry was performed to confirm that ERRα and HMGCS1 were related to EC progression. Furthermore, the mechanism was investigated using loss-of-function and gain-of-function assays or treatment with simvastatin. High expression levels of ERRα and HMGCS1 promoted intracellular cholesterol metabolism for invadopodia formation. Moreover, inhibiting ERRα and HMGCS1 expression significantly weakened the malignant progression of EC in vitro and in vivo. Our functional analysis showed that ERRα promoted EC invasion and metastasis through the HMGCS1-mediated intracellular cholesterol metabolism pathway, which was dependent on the epithelial-mesenchymal transition pathway. Our findings suggest that ERRα and HMGCS1 are potential targets to suppress EC progression.

Risk Factor Assessment of Lymph Node Metastasis in Patients With FIGO Stage IB1 Cervical Cancer.

Objectives: To assess the risk factors of lymph node metastasis (LNM) in patients with FIGO stage (2009) IB1 cervical cancer (CC). Methods: Patients with FIGO stage IB1 CC who underwent radical resection between 2012 and 2018 were recruited. The risk factors for LNM were analysed. A recursive partitioning analysis (RPA) was used to divide the patients into risk groups and assess their risk of LNM. Results: The 5-year overall survival rate was 91.72%, while 80.0% and 93.5% for patients with or without LNM (P<0.05). Multivariable logistic regression analysis showed that lymphovascular invasion (LVI), depth of invasion (DI), tumour size (TS), squamous cell carcinoma (SCC) antigen level were independent risk factors (all P<0.05). Patients were divided into low-risk (no LVI, DI <1/2, TS <2 cm), intermediate-risk (no LVI, DI <1/2, TS ≥2 cm; no LVI, DI ≥1/2, normal SCC level; LVI, DI <1/2, TS <2 cm), and high-risk (no LVI, DI ≥1/2, SCC level ≥1.5 ng/ml; LVI, TS <2 cm, DI ≥1/2; LVI, TS ≥2 cm) groups by RPA according to these four factors. The incidence of LNM among the three groups was 0.00%, 4.40%, and 24.10%, respectively (all P<0.001). The 5-year overall survival rates differed among the groups (98.2%, 92.7%, 83.0%, respectively, P=0.001). Conclusions: LNM affects the prognosis of patients with FIGO stage IB1 CC. Lymphadenectomy may be avoided for patients in the low-risk group and recommended for those in the high-risk group. Whether dissection is performed in the intermediate-risk group depends on the lymph node biopsy results.

Systemic Inflammatory Score predicts Overall Survival in patients with Cervical Cancer.

Background: To evaluate the prognostic value of the systemic inflammatory score (SIS) in cervical cancer patients. Methods: A total of 264 patients with FIGO stage (2009) IB-IIA cervical cancer undergoing radical resection from January 2014 to December 2017 were recruited. The optimal cutoff values for inflammatory biomarkers were calculated by X-tile software. The prognostic factors were investigated using univariate and multivariate Cox analyses. Time-dependent receiver operating characteristic (time-ROC) analysis and the concordance index (C-index) were used to compare the prognostic impact of factors. Results: In total, 264 patients with cervical cancer were included in the study. The optimal cutoff value for lymphocyte-to-monocyte ratio (LMR) was 4.1. In multivariate analysis, FIGO stage, lymphovascular invasion, lymph node metastasis, preoperative serum albumin (Alb), and LMR were independent prognostic factors (P<0.05). Then, we combined preoperative Alb and LMR to establish the SIS. Multivariate analysis showed that the SIS was an independent factor that affected survival (P<0.05). When stratified by FIGO stage, significant differences in survival were also found for patients with different SISs (P<0.05). When the SIS and FIGO stage were combined, the time-ROC curve was superior to that of FIGO stage only. The C-index of the model combining the SIS and FIGO stage was 0.786 (95% CI 0.699-0.873), which was significantly higher than that of the model with FIGO stage only (0.676, 95% CI 0.570-0.782, P=0.0049). Conclusions: The preoperative SIS is a simple and useful prognostic factor for postoperative survival in patients with cervical cancer. It might assist in the identification of high-risk patients among patients with the same FIGO stage.

Accurate detection of ß-hCG in women's serum and cervical secretions for predicting early pregnancy viability based on time-resolved luminescent lanthanide nanoprobes.

Sensitive and specific detection of ß-hCG in women's serum and cervical secretions is of great significance for early pregnancy evaluation. However, the accurate detection of trace amounts of ß-hCG in cervical secretions remains challenging because of its low level. Herein, we report a unique strategy for ß-hCG detection in a heterogeneous sandwich-type bioassay by using LiLuF4:Ce,Tb nanoparticles as time-resolved photoluminescence (PL) nanoprobes. By taking advantage of the intense and long-lived PL of the nanoprobes, the short-lived background autofluorescence can be completely eliminated, which enables the sensitive detection of ß-hCG with a linear range of 0-10 ng mL-1 and a detection limit down to 6.1 pg mL-1, approximately two orders of magnitude improvement relative to that of a commercial ß-hCG assay kit. Furthermore, we demonstrate the application of the nanoprobes for accurate detection of ß-hCG in clinical serum and cervical secretion samples and unveil that the ratio of ß-hCG levels in cervical secretions and serum can be a good indicator of early pregnancy viability in unknown locations. These findings bring new opportunities in perinatal medicine by employing luminescent lanthanide nanoprobes, thus laying a foundation for future development of luminescent nanoprobes for versatile biomedical applications.

A comparison study of post-operative infection analysis of cold-knife conization and loop electrosurgical excision procedure for cervical high-grade squamous intraepithelial lesion.

BACKGROUND: High-grade squamous intraepithelial lesion (HSIL) is a premalignant condition of the cervical cancer. Loop electrosurgical excision procedure (LEEP) and cold-knife conization (CKC) were the most effective treatment. Most studies focused on the recurrence rate, positive margin rate, residual disease rate, secondary hemorrhage or cervical stenosis of these two methods. At present, there are few researches about the post-operative infection comparing LEEP with CKC for treating HSIL. METHODS: One hundred and fourteen patients diagnosed as HSIL were underwent cold conization (n=43) or LEEP (n=71), according to 1:2 matching approximately and being divided randomly into two groups. The information, including the post-operational inflammatory complications, the leucorrhea abnormalities, the pathogens isolated from cervical secretions and pathological reports, were collected for comparison. RESULTS: There was no significant difference between them in bleeding, diameter, depth or volume of tissue between two groups. However, the operation time of the CKC group (24.81±11.09) minutes was longer than that of LEEP group (15.79±9.82) minutes. Seventeen patients of the LEEP group were admitted postoperatively as emergencies for secondary-hemorrhage. But it did not happen in CKC group. During the follow-up period, 28 patients (CKC 8 vs. LEEP 20) were diagnosis as reproductive tract infections. Fourteen patients (CKC 6 vs. LEEP 8) had leucorrhea abnormalities. Eighteen patient (CKC 3 vs. LEEP 15) isolated pathogens from their cervical secretions. There was no significant correlation between leucorrhea abnormality and cervical secretion abnormality. The positive rate of cervical secretion infection in the LEEP group was higher than the CKC group (P<0.05). The inflammatory response and process had some pathological difference in post-operation time of two groups, especially in those secondary hemorrhage cases. CONCLUSIONS: These two excision procedures for treating HSIL have their respective advantages and disadvantages. This study indicates that the incidence of persistent cervical infection after the CKC operation with Sturmdorf suturing is lower than that of after LEEP surgery. Clinicians should pay attention to the pathogen isolated from cervical post-operative secretion. It is conducive to find hidden pathogens and control subsequent surgical inflammation.

Phthalocyanine-based photosensitizer with tumor-pH-responsive properties for cancer theranostics.

Photodynamic therapy (PDT) has attracted attention for its potential for tumor destruction. We herein report a pH-responsive photosensitizer, synthesized by conjugating zinc phthalocyanine (ZnPc) with 2,4,6-tris(N,N-dimethylaminomethyl) phenoxy (TAP), which exhibited high phototoxicity at pH 6.5 (slightly acidic condition as in the extracellular tumor microenvironment) but no obvious phototoxicity at physiological pH 7.4. This pH-responsive photosensitizer specifically destroyed mouse mammary carcinoma cells 4T1 with an IC50 of 0.20 µM under a relatively low light dosage (2.5 J cm-2). The subsequent in vivo studies using 4T1-bearing mice demonstrated that this tumor-targeting photosensitizer ZnPc(TAP)4 not only ablated tumor cells photodynamically but also presented clear fluorescence cell imaging of tumor sites. These findings suggest that such a tumor-pH-responsive photosensitizer based on phthalocyanine may open up a new avenue for tumor-targeted and image-guided cancer theranostics in PDT.

[Influence of urodynamic factors on urinary retention in patients with cervical carcinoma after radical hysterectomy].

OBJECTIVE: To study the effect of urodynamic factors on the urinary retention of the patients with cervical cancer received radical hysterectomy. METHODS: Seventy-two patients with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage Ib1 to IIa hospitalized in Fujian Provincial Maternity and Child Health Hospital between June 2006 and August 2009, who were not found any abnormal representation of urodynamics before the operation, were divided into the group with urinary retention and the group without urinary retention based on whether urinary retention after the operation. All patients were detected by urodynamic examination following radical hysterectomy. Data obtained from urodynamic examination were analysed by logistic regression to evaluate the influence of urodynamic factors on the urinary retention postoperation. RESULTS: Twenty-one patients out of all were found with urinary retention after the operation, the incidence rate of urinary retention was 29%. The first sensation after operation in both groups were increased significantly than those before operation [(171 ± 61) ml vs. (126 ± 28) ml, (134 ± 39) ml vs. (119 ± 17) ml, all P < 0.05], while the maximum volume [(337 ± 66) and (300 ± 66) ml, respectively], the compliance [(31 ± 25) and (29 ± 18) ml/cm H2O (1 cm H2O = 0.098 kPa), respectively], the maximum flow rate [(10 ± 4) and (12 ± 5) ml/s, respectively] and the pressure at the maximum flow rate [(27 ± 9) and (32 ± 8) cm H2O, respectively] were decreased obviously after radical hysterectomy in both the group with urinary retention and the group without urinary retention (all P < 0.05), compared with the corresponding value before the operation. The urodynamic changes in urinary retention group was much more severe than those in group without urinary retention (P < 0.05). The single factor analysis results showed that bladder destusor dysfunction (OR = 8.20, 95%CI: 2.62-25.66, P < 0.01) and lack of sensation (OR = 6.90, 95%CI: 1.95-24.43, P < 0.01) were relevant to the urinary retention post-operation. While there were not relationship was found between low compliance bladder (OR = 1.99, 95%CI: 0.70-5.63, P = 0.195), detrusor overactivity (OR = 2.51, 95%CI: 0.73-8.67, P = 0.144), bladder outlet obstruction (OR = 3.77, 95%CI: 0.76-18.57, P = 0.104) or dyssynergia of urethral external sphincter (OR = 2.67, 95%CI: 0.49-14.45, P = 0.255) and urinary retention following the operation. There were an antagonistic effects (OR = 7.60, 95%CI: 1.43-40.39, P = 0.017) of detrusor overactivity and bladder destrusor dysfunction on urinary retention. The multiple factors analysis results revealed that bladder destusor dysfunction (OR = 7.01, P < 0.01) and lack of sensation (OR = 5.45, P = 0.018)were the independent risk factors influencing on the urinary retention post-operation. CONCLUSIONS: There are obvious urodynamic change in cervical cancer patients following radical hysterectomy. Bladder destrusor dysfunction and lack of sensation are the independent urodynamic risk factors influencing on urinary retention following radical hysterectomy, while detrusor over activity may be a protective effect on bladder destrusor dysfunction post-operation in some degree. Urodynamic test is important for analysis and treatment of urinary retention following radical hysterectomy.

[Effects of gamma-secretase inhibitor N-(3, 5-difluorophenacetyl-L-alanyl)-S-phenylglycine t-butyl ester on proliferation and differentiation of neural stem cells].

OBJECTIVE: To investigate the role of N-[N-(3,5-Difluorophenacetyl-L-alanyl)-S-phenylglycine t-butyl ester (DAPT), a gamma-secretases inhibitor, on the proliferation and differentiation of neural stem cells (NSCs). METHODS: NSCs were isolated from Sprague-Dawley rat brain, cultured, and treated with DAPT for 6 weeks. Cell counting was conducted every 24 h. CCK8 assay was used to draw the growth curve. Immunofluorescence staining was performed to observe the proportions of beta-tubulin III positive cells (neurons), glial fibrillary acidic protein (GFAP) positive cells (astrocytes), and 2',3'-cyclic nucleotide3' phosphohydrolase (CNPase) positive cells (oligodendrocytes). RT-PCR was employed to assay the mRNA expression of RBP-Jk and Hes1 genes, downstream genes of the Notch pathway. RESULTS: Cell counting and CCK-8 assay showed that DAPT reduced the rate of NSC proliferation. Addition of DAPT altered NSC differentiation in vitro, percentage of The proportions neurons of the DAPT group was (13.84 +/- 1.22)%, significantly higher than that of the control group [(3.7 +/- 1.04)% , P <0.01], the proportion of the oligodendrocytes of the DAPT group was (14.75 +/- 1.58)%, significantly higher than that pf the control group [(4.8 +/- 1.22)%, P < 0.01]. However, the proportion of astrocytes of the DAPT group was (63.41 +/- 1.20)%, significantly lower than that of the control group [ (82.84 +/- 3.68)%, P <0.01]. The expression levels of RBP-Jk and Hes1 mRNA (RBP-Jk/GAPDH and Hesl/GAPDH) in the NSC treated with DAPT were 0.52 +/- 0.13 and 0.66 +/- 0.18 respectively, both significantly lower than those of the control group (0.28 +/- 0.06 and 0.16 +/- 0.08 respectively, both P <0.05). CONCLUSION: DAPT inhibits the NSC proliferation and alters the NSC committed differentiation. These effects are mediated via Notch signaling down regulation as a result of the inhibition of gamma-secretase.