Ying Li

Association of plasma branched-chain amino acid with multiple cancers: A mendelian randomization analysis

Efficacy of a WeChat-Based, Multidisciplinary, Full-Course Nutritional Management Program on the Nutritional Status of Patients With Ovarian Cancer Undergoing Chemotherapy: Randomized Controlled Trial

Abstract Background As the most malignant type of cancer in the female reproductive system, ovarian cancer (OC) has become the second leading cause of death among Chinese women. Chemotherapy is the main treatment for patients with OC, and its numerous adverse effects can easily lead to malnutrition. It is difficult to centrally manage patients with OC in the intervals between chemotherapy. The use of WeChat, an effective mobile tool, in chronic disease management has been highlighted. Objective This study aimed to implement a continuous follow-up strategy and health monitoring based on the WeChat platform for patients with OC undergoing chemotherapy to ensure that each phase of chemotherapy was delivered on schedule and to improve the survival rate of patients with OC. Methods Participants were recruited and randomly assigned to either the WeChat-based nutrition intervention group or the usual care group. A self-administered general information questionnaire was used at enrollment to obtain basic information about the patients. The Patient-Generated Subjective Global Assessment (PG-SGA) Scale was used to investigate the nutritional status of the patients at 3 time points (T0=before the first admission to the hospital for chemotherapy, T1=2 weeks after the first chemotherapy, and T6=2 weeks after the sixth chemotherapy). The blood indices of patients were investigated through the inhospital health care system at 3 times（T0=before the first admission to the hospital for chemotherapy, T1=2 weeks after the first chemotherapy, and T6=2 weeks after the sixth chemotherapy). Patients in the intervention group were introduced to the nutrition applet, invited to join the nutrition management group chat, and allowed to consult on nutritional issues in private chats with nutrition management team members. Linear mixed models were used to analyze changes in each nutritional indicator in the 2 groups, with their baseline measurements as covariates; with group, time, and group-time interactions considered as fixed effects; and with patients considered as random effects. Results A total of 96 patients with OC undergoing chemotherapy were recruited into the study. Distribution was based on a 1:1 ratio, with 48 patients each in the nutrition intervention group and the usual care group. The attrition rate after the first chemotherapy session was 18.75%. The mixed linear model revealed that the group-based effect and the group-time interaction effect on PG-SGA scores were significant (F38,38=4.763, P=.03; F37,37=6.368, P=.01), whereas the time-based effect on PG-SGA scores was not (F38,38=0.377; P=.54). The findings indicated that the group-based effect, the time-based effect, and the group-time interaction effect on nutrition-inflammation composite indices were significant (F38,38=7.653, P=.006; F38,38=13.309, P<.001; F37,37=92.304, P<.001; F37,38=110.675, P<.001; F38,38=10.379, P=.002; and F37,37=5.289, P=.02). Conclusions This study provided evidence that a WeChat-based, multidisciplinary, full-course nutritional management program can significantly improve the nutritional status of patients with OC during chemotherapy.

Therapeutic targeting of CPSF3-dependent transcriptional termination in ovarian cancer

Transcriptional dysregulation is a recurring pathogenic hallmark and an emerging therapeutic vulnerability in ovarian cancer. Here, we demonstrated that ovarian cancer exhibited a unique dependency on the regulatory machinery of transcriptional termination, particularly, cleavage and polyadenylation specificity factor (CPSF) complex. Genetic abrogation of multiple CPSF subunits substantially hampered neoplastic cell viability, and we presented evidence that their indispensable roles converged on the endonuclease CPSF3. Mechanistically, CPSF perturbation resulted in lengthened 3′-untranslated regions, diminished intronic polyadenylation and widespread transcriptional readthrough, and consequently suppressed oncogenic pathways. Furthermore, we reported the development of specific CPSF3 inhibitors building upon the benzoxaborole scaffold, which exerted potent antitumor activity. Notably, CPSF3 blockade effectively exacerbated genomic instability by down-regulating DNA damage repair genes and thus acted in synergy with poly(adenosine 5'-diphosphate–ribose) polymerase inhibition. These findings establish CPSF3-dependent transcriptional termination as an exploitable driving mechanism of ovarian cancer and provide a promising class of boron-containing compounds for targeting transcription-addicted human malignancies.

A Review on Poly (ADP-ribose) Polymerase (PARP) Inhibitors and Synthetic Methodologies

Abstract:: Poly (ADP-ribose) polymerase (PARP) acts as an essential DNA repair enzyme. PARP inhibitors are novel small molecule targeted drugs based on the principle of "Synthetic Lethality", which affect DNA repair process by competitively inhibiting the activity of PARP enzyme and thereby kill cancer cells. Currently, four PARP inhibitors including olaparib, rucaparib, niraparib, and talazoparib have been approved by FDA for cancer treatment and have achieved great success in the treatment of ovarian cancer, breast cancer, and pancreatic cancer, etc. This paper provides a general overview of the research progress of PARP inhibitors including the major structure types, structure-activity relationship (SAR), and synthetic routes, with the aim of providing ideas for the discovery and synthesis of novel PARP inhibitors.

Dual Inhibition of CDK12/CDK13 Targets Both Tumor and Immune Cells in Ovarian Cancer

Abstract Therapeutic perturbation of cyclin-dependent kinase 12 (CDK12) is proposed to have pleiotropic effects in ovarian cancer, including direct cytotoxicity against tumor cells and indirect induction of immunogenicity that confer synthetic sensitivity to immune-based treatment. However, formal testing of this hypothesis has been hindered by an insufficient mechanistic understanding of CDK12 and its close homolog CDK13, as well as generally unfavorable pharmacokinetics of available CDK12/CDK13 covalent inhibitors. In this study, we used an innovative arsenous warhead modality to develop an orally bioavailable CDK12/CDK13 covalent compound. The dual CDK12/CDK13 inhibitors ZSQ836 exerted potent anticancer activity in cell culture and mouse models and induced transcriptional reprogramming, including downregulation of DNA damage response genes. CDK12 and CDK13 were both ubiquitously expressed in primary and metastatic ovarian cancer, and the two kinases performed independent and synergistic functions to promote tumorigenicity. Unexpectedly, although ZSQ836 triggered genomic instability in malignant cells, it counterintuitively impaired lymphocytic infiltration in neoplastic lesions by interfering with T-cell proliferation and activation. These findings highlight the Janus-faced effects of dual CDK12/CDK13 inhibitors by simultaneously suppressing tumor and immune cells, offering valuable insights into the future direction of drug discovery to pharmacologically target CDK12. Significance: This study dissects the specific roles of CDK12 and CDK13 in ovarian cancer and develops a CDK12/CDK13 inhibitor that impairs both tumor and immune cells, which could guide future CDK12 inhibitor development.

Head-to-Head Comparison of DH3 HPV Test and HC2 Assay for Detection of High-Risk HPV Infection in Residual Cytology Samples from Cervical Cancer Screening Setting: Baseline and 3-Year Longitudinal Data

The benefits of testing for high-risk human papillomavirus (hrHPV) in cervical cancer screening have already been demonstrated. Hybrid Capture 2 (HC2) is the best validated HPV assay and has been considered the gold standard for hrHPV testing.

Translation and Psychometric Evaluation of the Chinese Version of the Gynecological Cancers Awareness Scale

To translate the Gynecological Cancers Awareness Scale (GCAS) into Chinese and validate its reliability and validity in assessing awareness of gynecologic cancer prevention and treatment among women in China. Descriptive psychometric study. People's Republic of China. Adult women who lived in China (N = 434). We conducted the research in two phases. Phase 1 involved the translation and adaptation of the GCAS into Chinese. Phase 2 involved administering a cross-sectional survey using an electronic questionnaire. The translated GCAS had a Cronbach's α of .92, an intraclass correlation coefficient of 0.83, and an adequate content validity index. We used exploratory factor analysis to identify four factors that explained 64.01% of the variance and found that most fit indices in the confirmatory factor analysis were acceptable. Among our participants, the Chinese version of the GCAS was a valid and reliable tool for assessing awareness of gynecologic cancer risk, prevention, and treatment among women in China.