Development of an AIE-active fluorescent probe for the simultaneous detection of Al3+ and viscosity and imaging in Alzheimer's disease model.

Alzheimer's disease is associated both with imbalances in Al3+ production and changes in viscosity in cells. Their simultaneous measurement could therefore provide valuable insights into Alzheimer's disease pathology. Their simultaneous measurement would therefore be of great value in investigating the pathological mechanism of Alzheimer's disease. We designed a fluorescent probe YM2T with AIE effect that is capable of selectively responding to Al3+ by fluorescence colormetrics and to viscosity by fluorescence "turn on" modes. Additionally, Al3+ and viscosity were simultaneously detected in PC12 cells using the low cytotoxic probe YM2T via blue and green fluorescence channels. More importantly, the YM2T probe was used to image mice with AD. Hence, the YM2T probe shows potential as a useful molecular instrument for studying the pathological impact of Al3+ and viscosity.

Efficacy and influencing factors of CO2 laser, topical photodynamic therapy versus therapy combined with CO2 laser pretreatment for vaginal low-grade squamous intraepithelial lesions with high-risk HPV infection.

BACKGROUND: Vaginal intraepithelial neoplasia (VaIN) is a group of diseases of squamous epithelial dysplasia and carcinoma in situ occurring in the vagina, which is associated with high-risk human papillomavirus (HR-HPV) infection. OBJECTIVES: To evaluate the efficacy and safety of Carbon dioxide (CO2) laser, 5-aminolevulinic acid photodynamic therapy (PDT) and PDT combined with CO2 laser pretreatment for VaIN1 with HR-HPV infection, and analyze the factors affecting the clearance of HR-HPV. METHODS: Patients with HR-HPV infection and pathological diagnosis of VaIN1 and received laser or PDT or PDT combined with laser pretreatment were recruited. A total of 45 patients received one to three times CO2 laser (laser Group), 15 patients received three times PDT (PDT Group) and 15 patients received CO2 laser once and PDT three times (laser + PDT Group). HPV testing, cytology and colposcopy examinations at 3-6 months and 9-12 months after treatment were analyzed to assess the outcomes of the treatment. RESULTS: There was no significant difference in regression rate of VaIN1 among the laser Group, the PDT Group and the laser + PDT Group (3-6 month follow-up: 57.78% vs 73.3% vs 80 %, 9-12 month follow-up: 68.89% vs 80% vs 86.67 %, P>0.05). HR-HPV remission rates were also similar in the three groups (3-6 month follow-up: 26.67% vs 46.67% vs 46.67 %, 9-12 month follow-up: 40 % in all groups, P>0.05). Compared to HR-HPV negative group, patients in the HR-HPV positive group were older and had more pregnancies. Menopause and multiple vaginal lesions were more common in the HR-HPV positive group. Adverse reactions were mild in the PDT Group. The laser Group and the laser + PDT Group had more adverse effects, such as increased vaginal secretion, vaginal bleeding, scarring and local pain. CONCLUSION: For patients with VaIN1 at risk of progression, ALA-PDT presents itself as a viable choice for those who are well-informed and can consent to its costs and benefits. The addition of CO2 laser pretreatment may not increase the benefit of ALA-PDT treatment of VaIN1. Older age, menopause, more times of pregnancies, and multiple vaginal lesions might affect HR-HPV regression.

Optimising cervical cancer screening during pregnancy: a study of liquid-based cytology and HPV DNA co-test.

This study assessed the efficacy of ThinPrep cytologic test and human papillomavirus (HPV) co-test in cervical cancer screening during pregnancy. A cohort of 8,712 pregnant women from Ren Ji Hospital participated in the study. Among them, 601 (6.90%) tested positive for high-risk HPV (HR-HPV) and 38 (0.44%) exhibited abnormal cytology results (ASCUS+). Following positive HR-HPV findings, 423 patients underwent colposcopy, and 114 individuals suspected of having high-grade squamous intraepithelial lesion and cervical cancer (HSIL+) underwent cervical biopsy. Histological examination revealed 60 cases of normal pathology (52.63%), 35 cases of low-grade squamous intraepithelial lesion (30.70%), 17 cases of HSIL (14.91%), and 2 cases of cervical cancer (1.75%). The incidence of HSIL+ in HPV 16/18 group was significantly higher than that in non-HPV16/18 group (10.53% vs. 6.14%, P < 0.05). Subsequent evaluation of the clinical performance of cytology alone, primary HPV screening, and co-testing for HSIL+ detection revealed that the HSIL+ detection rate was lowest with cytology alone. These findings suggest that HPV testing, either alone or combined with cytology, presents an efficient screening strategy for pregnant women, underscoring the potential for improved sensitivity in cervical cancer screening during pregnancy. The significantly higher incidence of HSIL+ in the HPV16/18 group emphasizes the importance of genotype-specific considerations.

Analysis of outcomes following loop electrosurgical excision and clinical features of patients with cervical high-grade squamous intraepithelial lesions with abnormal preoperative endocervical curettage.

OBJECTIVE: The purpose of this study was to identify the clinical characteristics of patients with high-grade squamous intraepithelial lesions (HSIL) with abnormal endocervical curettage (ECC) and to evaluate the efficacy of abnormal preoperative ECC in predicting recurrence after a loop electrosurgical excision procedure (LEEP). METHODS: We retrospectively analyzed a total of 210 cases of histological HSIL in female patients diagnosed using cervical biopsy and/or indiscriminating ECC, and these included 137 cases with normal ECC and 63 cases with abnormal ECC. We also collected preoperative information and data on postoperative human papillomavirus (HPV) and histological outcomes within 2 years. RESULTS: The additional detection rate of HSIL using indiscriminating ECC was 5%. Patients with abnormal ECC were older (P < 0.001), predominantly menopausal (P = 0.001), had high-grade cytology (P = 0.032), a type 3 transformation zone (P = 0.046), and a higher proportion of HPV type 16/18 infection (P = 0.023). Moreover, age (odds ratio [OR] = 1.078, 95% confidence interval [CI] = 1.0325-1.1333, P = 0.003) and HPV 16/18 infection (OR = 2.082, 95% CI = 1.042-4.2163, P = 0.038) were independent risk factors for abnormal ECC. With an observed residual lesion/recurrence rate of 9.5% over the 24-month follow-up, we noted a 9.3% higher rate in the abnormal ECC group when compared with the normal ECC group. Abnormal preoperative ECC (OR = 4.06, 95% CI = 1.09-15.14, P = 0.037) and positive HPV at the 12-month follow-up (OR = 16.55, 95% CI = 3.54-77.37, P = 0.000) were independent risk factors for residual disease/recurrence. CONCLUSION: Preoperative ECC was one of the risk factors for post-LEEP residual/recurrent HSIL, and detecting abnormal ECC when managing older patients or patients with HPV 16/18 infection during colposcopy is critical.

Effect of topical 5-aminolevulinic acid photodynamic therapy versus therapy combined with CO2 laser pretreatment for patients with cervical high-grade squamous intraepithelial lesions.

OBJECTIVE: To evaluate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with CO2 laser pretreatment (Laser+ALA-PDT) on patients with cervical high-grade squamous intraepithelial lesions (HSILs). METHODS: A total of 114 patients treated by ALA-PDT or Laser+ALA-PDT at 3 centers were retrospectively reviewed. The effective rate, cure rate of lesions as well as high-risk human papillomavirus (HR-HPV) regression rate and persistent infection rate in the 2 groups were compared according to 3-6 month and 9-12 months follow-ups. The characteristics and risk factors for ineffective cases were evaluated by regression analysis. RESULTS: At the 3-6month follow-up, the effective rate was significantly higher in the Laser+ALA-PDT group than in the ALA-PDT group (96.6% vs. 81.3%, p = 0.048). A total of 79.3% of the laser+ALA-PDT patients achieved cure rate compared with 61.3% of the ALA-PDT patients (p = 0.082). In the Laser+ALA-PDT group, the HR-HPV-negative rate was significantly higher (72.4% vs. 50.7%, p = 0.045), while the persistence rate was significantly lower (20.7% vs. 42.7%, p = 0.037). At the 9-12month follow-up, the cure rate was 83% in the ALA-PDT group, 17% lower than that in the Laser+ALA-PDT group (p = 0.055). A total of 20.8% of patients in the ALA-PDT group and 5.3% in the Laser+ALA-PDT group showed persistent HR-HPV infection (p = 0.120). Pretreatment HR-HPV type, multiple infections and treatment modality were relevant factors for PDT outcome. CONCLUSIONS: For patients with cervical HSIL, laser+ALA-PDT shows better efficiency and HPV regression compared with ALA-PDT. HPV16/18 and multi-infection may be risk factors for ineffective treatment with ALA-PDT.

Feasibility study of 5-aminolevulinic acid mediated photodynamic therapy of persistent vaginal high-risk HPV infection of post-hysterectomy patients.

BACKGROUND: Patients after hysterectomy are at higher risk for developing VaIN. However, there are no standard treatments for HPV infection and VaIN after hysterectomy and relative studies are limited. Thus we aim to evaluate the feasibility of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) for the treatment of persistent vaginal infection with high-risk HPV (HR-HPV) in post-hysterectomy patients. METHODS: Thirty-eight patients aged 43-70 years old with persistent vaginal stump HR-HPV infection with or without histological vaginal intraepithelial neoplasia (VaIN1) during follow-up after hysterectomy were recruited. Twenty patients received three times of ALA-PDT (PDT Group). Eighteen patients did not receive any treatments (Control Group). HPV testing, cytology, and colposcopy were performed in all patients 4-6 months and 12 months after treatment. RESULTS: HR-HPV remission rates of the PDT Group were 40% (8/20) and 66.67% (12/18) at the 4-6 month and 12-month follow-up, respectively, both were significantly higher than that of the Control Group (11.11% (2/18) and 6.23% (1/16), respectively; P < 0.05). For the PDT Group, the regression rate of VaIN1 was 100% (7/7) at 4-6 months, while VaIN1 recurred in two cases (28.6%) at the 12-month due to persistent HR-HPV infection. No persistence or progression of VaIN1 was noted. For the Control group, the spontaneous regression rate of VaIN1 was 50% (3/6) at 4-6 months and one patient progressed into VaIN2. At the 12-month follow-up point, one patient reccurred and the disease regression, persistence and recurrence rates were 40% (2/5), 40% (2/5) and 20% (1/5), respectively. Adverse reactions were mild after PDT treatment. CONCLUSION: 5-ALA-PDT is a safe, non-invasive, and effective option for post-hysterectomy patients who have persistent HR-HPV infection.

Epidemiology and analysis of potential risk factors of high-risk human papillomavirus (HPV) in Shanghai China: A cross-sectional one-year study in non-vaccinated women.

Data regarding human papillomavirus (HPV) prevalence, its associated risk factors, and women's knowledge about this disease before the HPV vaccine was approved are limited in Shanghai, China. Therefore, we investigated these questions among females in Shanghai and aimed to provide comprehensive data to guide HPV vaccination and present the biopsychosocial risk factors that impact high-risk HPV infection, and evaluate the level of knowledge and awareness of this disease among women aged 21-65 years old. A total of 6619 (aged from 21 to 65) women from different communities volunteered to participate in the HPV screening and complete questionnaires from December 2016 to December 2017 in the Department of Obstetrics and Gynecology of nine hospitals in Shanghai. Data were analyzed using sample logistic regression to assess biopsychosocial risk factors that impact high-risk HPV infection and knowledge of HPV infection. A total of 632 (9.5%) cases were positive for high-risk HPV test, 22.6% of them were HPV 16/18 infection, 77.4% of them were non HPV 16/18 infection. 40 potential risk factors may be related to high-risk HPV infection, and there were 19 factors' p value < 0.1 from single factor logistic analysis. Finally, multivariable regression revealed education level, type of vaginitis, history of hyperlipidemias, family history of cancer, number of pregnancies, number of sex partners were independent risk factors for high-risk HPV infection (p < 0.05). When stratified by education level, women who finished graduate school had significantly greater knowledge of cervical cancer, cervical screening, and the relationship between HPV and cervical cancer than other groups (p < 0.05). The prevalence rate of high-risk HPV was a little lower than other regions in China and other countries, which may be related to regions, races, living habits, and economy. A less reported finding is that the history of vaginitis and the history of hyperlipidemias in our study were related to HPV infection. The majority of the participants had poor knowledge regarding cervical cancer, cervical screening, and the relationship between HPV and cervical cancer. Hence, these results should be served as a wake-up call for the government to increase knowledge and awareness via the media and doctors.

Clinical evaluation of a real-time optoelectronic device in cervical cancer screening.

OBJECTIVE: Early screening and intervention are crucial for the prevention and treatment of cervical cancer. TruScreen is a real-time, intelligent, pathological diagnostic technology designed for cervical cancer screening. The aim of this study was to evaluate the clinical value of TruScreen in screening for cervical lesions. STUDY DESIGN: A total of 458 women aged between 25 and 65 years were recruited to receive cervical cancer screening, including human papillomavirus (HPV) testing, cytological testing using the ThinPrep cytology test (TCT), and TruScreen from December 2018 to January 2020. The clinical performance of TruScreen, alone and in combination with HPV testing, was evaluated to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+ or CIN3+). RESULTS: For detection of CIN2+, the sensitivity and specificity of TruScreen were 83.78% and 78.86%, respectively. The specificity of TruScreen was significantly higher than those of HPV testing (50.59%, P < 0.001) and TCT (55.58%, P < 0.001). In high-risk HPV-positive women, the specificity of HPV testing combined with TruScreen was significantly higher than that of HPV testing combined with TCT (50% vs 39.9%, P = 0.004). The sensitivity of HPV testing combined with TruScreen was comparable to that of HPV testing combined with TCT (93.94% vs 87.88%, P = 0.625). Similar patterns were also observed for CIN3+ cases. CONCLUSION: TruScreen has the potential for screening high-grade cervical precancerous lesions and may replace cytological tests as a cervical cancer screening method in China to avoid subjectivity in the interpretation of cytological tests and requirements by pathologists.

Characterization of a complete mitochondrial genome of Turdus ruficollis (Passeriformes: Turdidae).

Turdus ruficollis is mainly found in China and Northeast Asia. So far, the mitochondrial genome of more than 20 species from the genus Turdus has been studied. However, the relevant information of T. ruficollis has not been reported. To grasp a better comprehension on the molecular basis of T. ruficollis, we obtained the complete mitochondrial DNA genome sequences of this species. The mitogenome was 16,737 bp in length, which consists of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one control region. A phylogenetic tree based on complete mitogenome sequences revealed that, within the genus Turdidae, T. ruficollis is closely related to T. naumanni and T. eumomus. The complete mitochondrial genome of T. ruficollis would be of great utility for population genetics and phylogeography of the Turdidae family and would also provide meritorious insights for future studies on conservation, genetics, and phylogeny of the Passeriformes family.

The role of high mobility group protein B3 (HMGB3) in tumor proliferation and drug resistance.

The high mobility group protein B (HMGB) family (including HMGB1, HMGB2, HMGB3, and HMGB4) can regulate the mechanisms of DNA replication, transcription, recombination, and repair, and act as cytokines to mediate responses to infection, injury, and inflammation. HMGB1/2/3 has a high similarity in sequence and structure, while HMGB4 has no acidic C-terminal tail. Among them, HMGB3 can regulate the self-renewal and differentiation of normal hematopoietic stem cell population, but the decrease of its expression is easy to induce leukemia. Up-regulation of its expression promotes tumor development and chemotherapy resistance through a variety of mechanisms, and non-coding RNA can regulate to promote tumor cell proliferation, invasion, and migration and inhibit cancer cell apoptosis.

Role of immune escape in different digestive tumours.

A counterbalance between immune cells and tumour cells is key to fighting tumours, and immune escape is an important mechanism for the survival of tumour cells in the body. Tumor cells and their cytokines impair the activity of T cells, NK cells, macrophages and other immune cells through various ways, and change the expression of their own surface antigens so as to avoid the clearance of the immune system. Changes in major histocompatibility complex molecules, high expression of programmed death-ligand 1, and the presence of immunosuppressive cells in the tumor microenvironment (TME) are main means by which tumors impair the function of immune cells. During the development of tumours of the digestive system, different mechanisms acting on tumour cells, the TME, and immune cells lead to immune escape and promote tumour progression. In this paper, the mechanisms of immune escape in tumour cells of the digestive system are reviewed to provide a theoretical basis for the immunotherapy of gastrointestinal tumours.

The molecular mechanisms of celecoxib in tumor development.

BACKGROUND: Clinical studies have shown that celecoxib can significantly inhibit the development of tumors, and basic experiments and in vitro experiments also provide a certain basis, but it is not clear how celecoxib inhibits tumor development in detail. METHODS: A literature search of all major academic databases was conducted (PubMed, China National Knowledge Internet (CNKI), Wan-fang, China Science and Technology Journal Database (VIP), including the main research on the mechanisms of celecoxib on tumors. RESULTS: Celecoxib can intervene in tumor development and reduce the formation of drug resistance through multiple molecular mechanisms. CONCLUSION: Celecoxib mainly regulates the proliferation, migration, and invasion of tumor cells by inhibiting the cyclooxygenases-2/prostaglandin E2 signal axis and thereby inhibiting the phosphorylation of nuclear factor-κ-gene binding, Akt, signal transducer and activator of transcription and the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. Meanwhile, it was found that celecoxib could promote the apoptosis of tumor cells by enhancing mitochondrial oxidation, activating mitochondrial apoptosis process, promoting endoplasmic reticulum stress process, and autophagy. Celecoxib can also reduce the occurrence of drug resistance by increasing the sensitivity of cancer cells to chemotherapy drugs.