Factors associated with health-related quality of life in papillary thyroid microcarcinoma patients undergoing radiofrequency ablation: a cross-sectional prevalence study.

PURPOSE: To explore the association of demographic characteristics, clinical symptoms and the fear of the disease progression factors with the physical and mental summary components of the health-related of life (HRQoL) of the papillary thyroid microcarcinoma (PTMC) patients undergoing radiofrequency ablation (RFA). METHODS: 123 PTMC survivors undergoing RFA were enrolled in this study from October 2019 to March 2020. Demographic, clinical symptoms and the fear of the disease progression data were collected. SF-36, THYCA-QoL and FoP-Q-SF were used to evaluate the HRQoL of patients, clinical symptoms and the fear of disease progression. A multivariate regression model was performed to evaluate the association between the independent variable and the HRQoL variable. RESULTS: The average self-reported HRQoL score was 81.17 ± 15.48 for the PCS and 73.40 ± 18.03 for the MCS. The multivariate linear regression model shows that the factors related to a poorer PCS were dependent for the female patients, the symptoms of neuromuscular and the throat/mouth, the fear of disease progression; the psychological disorder, symptoms of throat/mouth, inability to concentrate were related to worse scores for the MCS. The condition that was most strongly related to a poorer HRQoL (in both PCS and MCS) was the fear of their physical health. CONCLUSIONS: The factors related to significantly worse HRQoL scores across PCS and MCS for PTMC survivors include the female gender, the symptoms of neuromuscular and the throat/mouth, the psychological disorder, inability to concentrate, and the fear of their own physical health. Identification, management, and prevention of these factors are critical to improving the HRQoL of patients.

[Factors Affecting Quality of Life of Patients Undergoing Radiofrequency Ablation for Papillary Thyroid Microcarcinoma].

Objective To evaluate the factors affecting health-related quality of life (HRQoL) of patients with thyroid papillary microcarcinoma (PTMC) after ultrasound-guided radiofrequency ablation (RFA).Methods The clinical data of 100 patients with PTMC who underwent reexamination after RFA in the Ultrasound Department of our center from October to December 2019 were retrospectively analyzed.Demographic information was collected.SF-36 and Thyroid Cancer-specific Health-related Quality of Life Questionnaire scales were used to assess patients' quality of life and thyroid-related specific symptoms.The SF-36 scale includes two general domains including physical component summary (PCS) and mental component summary (MCS).The impacts of demographic characteristics and thyroid-related symptoms after RFA on PCS and MCS scores were further analyzed.Results Univariate analysis and correlation analysis showed that the PCS scores in quality of life of PTMC patients were related to sex, neuromuscular, voice, concentration, sympathetic nerve, and throat/mouth complaints, psychological state, sensory symptoms, scar, chills, tingling, and headache (all P<0.1);and the MCS scores were associated with education level, residence, neuromuscular, voice, concentration, sympathetic nerve, and throat/mouth complains, psychological state, sensory symptoms, scar, chills, tingling, and headache (all P<0.1).Multivariate regression analysis showed that the PCS scores were only associated with sex and the neuromuscular and throat/mouth complains and the psychological state.The regression equation was:PCS=110.367-8.025×sex-0.213×psychological state-0.280×neuromuscular complain-0.278×throat/mouth complain.In contrast, the MCS scores were only associated with the psychological state and the throat/mouth and concentration complains, with the regression equation being:MCS=91.323-0.237×psychological state-0.437×throat/mouth-0.304×concentration.Conclusions The main risk factors affecting the quality of life of PTMC patients after ultrasound-guided RFA were female gender, psychological burden, lack of attention, and symptoms in neuromuscular system and throat/mouth.Therefore, preoperative explanations should be made according to the relevant symptoms that the patients may report, and psychological interventions should be offered after RFA to improve the quality of life of PTMC patients after treatment.

Hyperbranched poly(ß-amino ester) based polyplex nanopaticles for delivery of CRISPR/Cas9 system and treatment of HPV infection associated cervical cancer.

Persistent high-risk HPV infection is the main factor for cervical cancer. HPV E7 oncogene plays an important role in HPV carcinogenesis. Down-regulation of E7 oncogene expression could induce growth inhibition in HPV-positive cells and thus treats HPV related cervical cancer. Here we developed a non-virus gene vector based on poly(amide-amine)-poly(ß-amino ester) hyperbranched copolymer (hPPC) for the delivery of CRISPR/Cas9 system to specifically cleave HPV E7 oncogene in HPV-positive cervical cancer cells. The diameter of polyplex nanoparticles (NPs) formed by hPPCs/linear poly(ß-amino ester) (PBAE) and plasmids were approximately 300 nm. These hPPCs/PBAE-green fluorescence protein plasmids polyplex NPs showed high transfection efficiency and low toxicity in cells and mouse organs. By cleaving HPV16 E7 oncogene, reducing the expression of HPV16 E7 protein and increasing intracellular retinoblastoma 1 (RB1) amount, hPPCs/PBAE-CRISPR/Cas9 therapeutic plasmids polyplex NPs, especially highly branched hPPC1-plasmids polyplex NPs, exhibited strong growth inhibition of cervical cancer cells in vitro and xenograft tumors in nude mice. Together, the hPPCs/PBAE polyplex NPs to deliver HPV16 E7 targeted CRISPR/Cas9 system in this study could potentially be applied to treat HPV-related cervical cancer.

An effective vaginal gel to deliver CRISPR/Cas9 system encapsulated in poly (ß-amino ester) nanoparticles for vaginal gene therapy.

BACKGROUND: Gene therapy has held promises for treating specific genetic diseases. However, the key to clinical application depends on effective gene delivery. METHODS: Using a large animal model, we developed two pharmaceutical formulations for gene delivery in the pigs' vagina, which were made up of poly (ß-amino ester) (PBAE)-plasmid polyplex nanoparticles (NPs) based two gel materials, modified montmorillonite (mMMT) and hectorite (HTT). FINDINGS: By conducting flow cytometry of the cervical cells, we found that PBAE-GFP-NPs-mMMT gel was more efficient than PBAE-GFP-NPs-HTT gel in delivering exogenous DNA intravaginally. Next, we designed specific CRISPR/SpCas9 sgRNAs targeting porcine endogenous retroviruses (PERVs) and evaluated the genome editing efficacy in vivo. We discovered that PERV copy number in vaginal epithelium could be significantly reduced by the local delivery of the PBAE-SpCas9/sgRNA NPs-mMMT gel. Comparable genome editing results were also obtained by high-fidelity version of SpCas9, SpCas9-HF1 and eSpCas9, in the mMMT gel. Further, we confirmed that the expression of topically delivered SpCas9 was limited to the vagina/cervix and did not diffuse to nearby organs, which was relatively safe with low toxicity. INTERPRETATION: Our data suggested that the PBAE-NPs mMMT vaginal gel is an effective preparation for local gene therapy, yielding insights into novel therapeutic approaches to sexually transmitted disease in the genital tract. FUNDING: This work was supported by the National Science and Technology Major Project of the Ministry of science and technology of China (No. 2018ZX10301402); the National Natural Science Foundation of China (81761148025, 81871473 and 81402158); Guangzhou Science and Technology Programme (No. 201704020093); National Ten Thousand Plan-Young Top Talents of China, Fundamental Research Funds for the Central Universities (17ykzd15 and 19ykyjs07); Three Big Constructions-Supercomputing Application Cultivation Projects sponsored by National Supercomputer Center In Guangzhou; the National Research FFoundation (NRF) South Africa under BRICS Multilateral Joint Call for Proposals; grant 17-54-80078 from the Russian Foundation for Basic Research.