Flavokawain B inhibits NF-κB inflammatory signaling pathway activation in inflammatory bowel disease by targeting TLR2.

Inflammatory bowel disease (IBD) is characterized by recurrent inflammatory reactions in the intestinal mucosa, including ulcerative colitis (UC) and Crohn's disease (CD). The expression of Toll-like receptor 2 (TLR2) has been observed to increase during the progression of IBD. Flavokawain B (FKB), a natural chalcone with potent anti-inflammatory activity, exerts its effects through inhibition of the NF-κB pathway. In this study, we aimed to investigate the effects and mechanisms of FKB targeting TLR2 in IBD. C57BL/6 J mice were treated with 2.5% dextran sulfate sodium (DSS) for 7 days, with administration of FKB or TLR2 inhibitor C29 starting on day 2 to establish the model of IBD. In vitro, bone marrow-derived macrophages (BMDMs) were stimulated with the TLR2 agonist Pam3CSK4 to explore the therapeutic effect of FKB and its pharmacological mechanism. Compared with the model group, the FKB-treated group showed significant reductions in colitis-related injuries in the IBD mouse model, including weight gain, increased colon length and reduced inflammation. FKB decreased the formation of TLR2-MyD88 complex by targeting TLR2, leading to suppression of downstream NF-κB signaling pathway. Similar therapeutic effects were observed in the C29-treated group. Additionally, in vitro data suggested that FKB exerted its anti-inflammatory effect by targeting TLR2 and inhibiting Pam3CSK4-induced activation of the NF-κB pathway. The anti-inflammatory effects of FKB were demonstrated through drug affinity responsive target stability assay and cellular thermal shift assay, revealing its binding affinity to TLR2. By inhibiting the activation of the TLR2/NF-κB signaling pathway, FKB effectively prevented DSS-induced IBD and exhibited promising potential as a therapeutic candidate for IBD treatment.

Assessing health-related quality of life of Chinese population using CQ-11D.

PURPOSE: This study aimed to assess the health-related quality of life (HRQoL) of the Chinese population by using the Chinese medicine quality of life-11 dimensions (CQ-11D) questionnaire and to identify factors associated with HRQoL. METHODS: The data was derived from a survey conducted by the Institute of Pharmacoeconomics Evaluation at Beijing University of Chinese Medicine on the quality of life of the Chinese population. The sex and age of respondents were considered through quota sampling. Demographic, socioeconomic, and health indicators were collected using the structured questionnaire. We performed bivariate analyses first to examine the associations between the above factors and the HRQoL of respondents measured by the CQ-11D. Multivariate linear regression and ordinal logistic regression models were established to analyze the factors (demographic, socioeconomic, and health indicators) differences in HRQoL, as well as the risk of each group reporting problems across the 11 dimensions of CQ-11D. RESULTS: From February 2021 to November 2022, a total of 7,604 respondents were involved and 7,498 respondents were included. The sample approximated the general adult Chinese population in terms of age, sex, and district of residence, and each geographic distribution ranged from 9.71 to 25.54%. Of the respondents, 45.84% were male, and 89.82% were Han ethnicity. The mean utility score ranged from 0.796 to 0.921 as age increased. According to the respondents, most health problems were identified in the PL (fatigue) (70.16%) and SM (quality of sleep) (63.63%) dimensions. The CQ-11D index scores varied with the demographic and socioeconomic characteristics of respondents, except for ethnicity (p > 0.05) and income (p > 0.05). The multivariate analysis revealed significant negative associations between health utility scores and various factors. These factors include sex (female), age over 65, belonging to ethnic minorities, rural household registration, being widowed or divorced, having a primary school education or below, being a student or unemployed, having a low income of 0-1,300, engaging in smoking or drinking, limited participation in physical activities, experiencing changes in self-perceived health status compared to the previous year, and having chronic diseases. The odds of respondents reporting problems in 11 dimensions varied among different socio-demographic groups. CONCLUSIONS: This study reports the first Chinese population norms for the CQ-11D derived using a representative sample of the Chinese general population. Self-reported health status measured by the CQ-11D varies among different socio-economic groups. In addition to participation a physical activity and the presence of chronic disease, smoking and drinking also significantly influence HRQoL.

Costunolide alleviates hyperglycaemia-induced diabetic cardiomyopathy via inhibiting inflammatory responses and oxidative stress.

Hyperglycaemia-induced myocardial injury promotes the induction of heart failure in diabetic patients. Impaired antioxidant capability and sustained chronic inflammation play a vital role in the progression of diabetic cardiomyopathy (DCM). Costunolide (Cos), a natural compound with anti-inflammatory and antioxidant properties, has exhibited therapeutic effects in various inflammatory diseases. However, the role of Cos in diabetes-induced myocardial injury remains poorly understood. In this study, we investigated the effect of Cos on DCM and explored the potential mechanisms. C57BL/6 mice were administered intraperitoneal streptozotocin for DCM induction. Cos-mediated anti-inflammatory and antioxidation activities were examined in heart tissues of diabetic mice and high glucose (HG)-stimulated cardiomyocytes. Cos markedly inhibited HG-induced fibrotic responses in diabetic mice and H9c2 cells, respectively. The cardioprotective effects of Cos could be correlated to the reduced expression of inflammatory cytokines and decreased oxidative stress. Further investigations demonstrated Cos reversed diabetes-induced nuclear factor-κB (NF-κB) activation and alleviated impaired antioxidant defence system, principally via activation of nuclear factor-erythroid 2 p45-related factor-2 (Nrf-2). Cos alleviated cardiac damage and improved cardiac function in diabetic mice by inhibiting NF-κB-mediated inflammatory responses and activating the Nrf-2-mediated antioxidant effects. Therefore, Cos could be a potential candidate for the treatment of DCM.

Valuing Chinese medicine quality of life-11 dimensions (CQ-11D) health states using a discrete choice experiment with survival duration (DCETTO).

OBJECTIVE: To explore generating a health utility value set for the Chinese medicine Quality of life-11 Dimensions (CQ-11D), a utility instrument designed to assess patients' health status while receiving TCM treatment, among the Chinese population. METHODS: The study was designed to recruit at least 2400 respondents across mainland China to complete one-to-one, face-to-face interviews. Respondents completed ten discrete choice experiment with survival duration (DCETTO) tasks during interviews. The conditional logit models were used to generate the health utility value set for the CQ-11D using the DCETTO data. RESULTS: A total of 2,586 respondents were invited to participate in the survey and 2498 valid interviews were completed (a completion rate of 96.60%). The modified conditional logit model with combing logically inconsistent levels was ultimately selected to construct the health utility value set for the CQ-11D instrument. The range of the measurable health utility value was -0.868 ~ 1. CONCLUSION: The study provides the first utility value set for the CQ-11D among the Chinese population. The CQ-11D and corresponding utility value set can be used to measure the health utility values of patients undergoing traditional Chinese medicine interventions, and further facilitate relevant cost-utility analyses. The application of the CQ-11D can support TCM resource allocation in China.

Tabersonine attenuates obesity-induced renal injury via inhibiting NF-κB-mediated inflammation.

Obesity-induced metabolic disorders can cause chronic inflammation in the whole body, activating the nuclear factor kappa B (NF-κB) pathway and inducing apoptosis. Therefore, anti-inflammatory strategies may be effective in preventing obesity-related renal injury. Tabersonine (Tab) has been used pharmacologically to alleviate inflammation-related symptoms. This study evaluated the therapeutic effect of Tab on obesity-related renal injury and explored the pharmacological mechanism. Tab (20 mg/kg) relieved HFD-induced renal structural disorder and alleviated renal functional decline in mice, including improvement of renal tissue fibrosis, reducing renal cell apoptosis and inflammation in renal tissues. Mechanistically, we demonstrated that Tab inhibited the activation of NF-κB signaling pathway both in vivo and in vitro, thereby improving the renal tissue lesions in the mice with obesity-related renal injury. In both the obese mouse model and the mouse glomerular mesangial cell model, the natural compound Tab ameliorated HFD- and saturated fatty acid-induced renal cell injury by inhibiting the activation of NF-κB signaling pathway. Our data suggest that Tab may become a potential candidate for the prevention and treatment of obesity-related renal injury.

Real-world data of 14 cases of brain metastases from gestational trophoblastic neoplasia and a literature review.

OBJECTIVE: The aim of this study was to investigate the diagnosis, treatment, and prognosis of patients with brain metastases from gestational trophoblastic neoplasia (GTN) in the real world. METHODS: Analyzing the clinicopathological characteristics, treatment process, and prognosis of 14 GTN patients with brain metastases admitted to the West China Second University Hospital between January 2006 and December 2020. RESULTS: The median FIGO prognostic score was 15 points (range 11-21 points), with 12 cases having 13 points or more (extremely high risk). All patients received combination chemotherapy. The first-line regimen included 5-Fluorouracil, dactinomycin, and intrathecal methotrexate (5-FU + KSM + intrathecal MTX), and etoposide + methotrexate + actinomycin D/cyclophosphamide and vincristine (EMA-CO). Two patients died during the early period after diagnosis of brain metastases. A further patient with GTN Stage III failed to achieve a negative serum ß human chorionic gonadotropin (hCG) after receiving chemotherapy in another hospital. Ten months after self-discontinuation of treatment, the disease progressed and she was admitted to our hospital with suspected liver and brain metastases, after which she abandoned treatment and was lost to follow-up. Among the remaining 11 patients, one relapsed once and two relapsed three times. Aside from the two patients who died and the one who was lost to follow-up, the remaining 11 patients had a median follow-up time of 89 months (range 35-148 months) and all achieved complete remission. CONCLUSION: The overall survival rate of the patients in the present study was 78.57% through combination chemotherapy, symptomatic treatment, and co-treatment with brain radiotherapy for some patients. Enhancing the understanding of this disease and standardizing treatment are key to improving the overall survival rate of GTN patients with brain metastases.

[Pharmacoeconomic evaluation of Suhuang Zhike Capsules using Markov model for inpatients with acute exacerbation of chronic obstructive pulmonary disease].

To evaluate the economics of Suhuang Zhike Capsules in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) for inpatients. Based on the published clinical research data, cost-utility analysis was used in this study to evaluate the pharmacoeconomics of Suhuang Zhike Capsules in treatment of AECOPD inpatients from the perspective of medical insu-rance. The test group was treated with Suhuang Zhike Capsules combined with conventional Western medicine, and the control group was treated with conventional Western medicine alone. Treeage software was used to construct a pharmacoeconomic model and perform simulation analysis. The results showed that the cost and output of Suhuang Zhike Capsules combined with the conventional Western medicine were 60 010.18 yuan and 1.92 quality adjusted life year(QALYs), respectively in the simulated 3 years of disease treatment. The cost and output of the conventional Western medicine were 96 730.60 yuan and 1.90 QALYs respectively. Suhuang Zhike Capsules combined with conventional Western medicine required lower cost but achieved higher output, showing cost-utility advantages, so this drug combination was a plan with pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is believed that as compared with the conventional Western medicine, Suhuang Zhike Capsules combined with conventional Western medicine have lower cost and higher output for the treatment of AECOPD inpatients, and it is a treatment plan with pharmacoeconomic advantages.

Clinicopathological significance and prognosis of long noncoding RNA SNHG16 expression in human cancers: a meta-analysis.

BACKGROUND: Recent studies have highlighted the important role of long non-coding RNA SNHG16 in various human cancers. Here, we conducted a meta-analysis to investigate the effect of SNHG16 expression on clinicopathological features and prognosis in patients with different kinds of human cancers. METHODS: We performed a systematic search in electronic databases including PubMed, EMBASE, Cochrane Library and Web of Science, to investigate the potential association between SNHG16 expression and prognostic significance and clinical features in cancer patients. Odds ratios (ORs) or hazards ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were pooled to estimate the prognosis value of SNHG16 by StataSE 15.0 software. RESULTS: A total of 16 eligible studies with 1299 patients were enrolled in our meta-analysis. The results revealed that increased expression level of SNHG16 was significantly associated with larger tumor size (OR: 3.357; 95% CI: 2.173-5.185; P < 0.001), advanced TNM stage (OR: 2.930; 95% CI: 1.522-5.640; P = 0.001) and poor histological grade (OR: 3.943; 95% CI: 1.955-7.952; P < 0.001), but not correlated with smoking status (P = 0.489), sex (P = 0.932), distant metastasis (P = 0.052), or lymph node metastasis (P = 0.155). Moreover, the pooled HR showed that elevated expression SNHG16 was associated with a significantly poorer overall survival (OS) (HR = 1.866, 95% CI: 1.571-2.216, P < 0.001). For the set of cancer types, high expression of SNHG16 was significantly associated with shorter OS in patients with cancers of the urinary system (HR: 2.523, 95% CI:1.540-4.133; P <0.001), digestive system (HR: 2.406, 95% CI:1.556-3.721; P <0.001), and other cancers (including glioma and non-small cell lung cancer) (HR: 1.786, 95% CI:1.406-2.267; P <0.001). CONCLUSIONS: LncRNA SNHG16 overexpression might serve as an unfavorable prognostic factor, which provides a basis for medical workers to evaluate the prognosis of patients and to help the decision-making process.

[Efficacy, safety and cost of Qianlieshutong Capsules in the treatment of chronic prostatitis].

OBJECTIVE: To comprehensively evaluate the clinical effect, safety and cost of Qianlieshutong Capsules (QC) in the treatment of chronic prostatitis. METHODS: We searched Cochrane Library, PubMed, Springer, ProQuest, CNKI, Wanfang Data and VIP for randomized controlled trials (RCT) on the treatment of chorionic prostatitis with QC published from January 2000 to May 2018. According to the inclusion and exclusion criteria, two researchers independently completed the screening and evaluation of the articles, extraction of information, and meta-analysis of the included RCTs using the RevMan 5.3 software. RESULTS: Totally 10 RCTs involving 1 796 cases were included in this study, in which the chronic prostatitis patients treated by the combination of QC and quinolones all showed a significantly better response than the controls (P < 0.05). QC combined with quinolones cost an average of ¥23 more than quinolones alone with a 1% increase of therapeutic effectiveness, ¥38.39 more with a 1-unit reduction of WBCs, and ¥38.84 more with a 1-point decrease in the NIH-CPSI score. CONCLUSIONS: The combination of QC with quinolones has a better therapeutic efficacy but a higher cost than quinolones alone in the treatment of chronic prostatitis.

Advances and challenges in the origin and evolution of ovarian cancer organoids.

Despite advancements in cancer research, epithelial ovarian cancer remains a leading threat to women's health with a low five-year survival rate of 48%. Prognosis for advanced cases, especially International Federation of Gynecology and Obstetrics (FIGO) III-IV, is poor. Standard care includes surgical resection and platinum-based chemo, but 70-80% face recurrence and chemoresistance. In recent years, three- dimensional (3D) cancer models, especially patients-derived organoids (PDOs), have revolutionized cancer research for personalized treatment. By transcending the constraints of conventional models, organoids accurately recapitulate crucial morphological, histological, and genetic characteristics of diseases, particularly in the context of ovarian cancer. The extensive potential of ovarian cancer organoids is explored, spanning from foundational theories to cutting-edge applications. As potent preclinical models, organoids offer invaluable tools for predicting patient treatment responses and guiding the development of personalized therapeutic strategies. Furthermore, in the arena of drug evaluation, organoids demonstrate their unique versatility as platforms, enabling comprehensive testing of innovative drug combinations and novel candidates, thereby pioneering new avenues in pharmaceutical research. Notably, organoids mimic the dynamic progression of ovarian cancer, from inception to systemic dissemination, shedding light on intricate and subtle disease mechanisms, and providing crucial insights. Operating at an individualized level, organoids also unravel the complex mechanisms underlying drug resistance, presenting strategic opportunities for the development of effective treatment strategies. This review summarizes the emerging role of ovarian cancer organoids, meticulously cultivated cellular clusters within three-dimensional models, as a groundbreaking paradigm in research.

Causal association between circulating inflammatory markers and sciatica development: a Mendelian randomization study.

Background: This research explores the causal association between circulating inflammatory markers and the development of sciatica, a common and debilitating condition. While previous studies have indicated that inflammation may be a factor in sciatica, but a thorough genetic investigation to determine a cause-and-effect relationship has not yet been carried out. Gaining insight into these interactions may uncover novel treatment targets. Methods: We utilized data from the OpenGWAS database, incorporating a large European cohort of 484,598 individuals, including 4,549 sciatica patients. Our study focused on 91 distinct circulating inflammatory markers. Genetic variations were employed as instrumental variables (IVs) for these markers. The analysis was conducted using inverse variance weighting (IVW) as the primary method, supplemented by weighted median-based estimation. Validation of the findings was conducted by sensitivity studies, utilizing the R software for statistical computations. Results: The analysis revealed that 52 out of the 91 inflammatory markers studied showed a significant causal association with the risk of developing sciatica. Key markers like CCL2, monocyte chemotactic protein-4, and protein S100-A12 demonstrated a positive correlation. In addition, there was no heterogeneity or horizontal pleiotropy in these results. Interestingly, a reverse Mendelian randomization analysis also indicated potential causative effects of sciatica on certain inflammatory markers, notably Fms-related tyrosine kinase 3 ligands. Discussion: The study provides robust evidence linking specific circulating inflammatory markers with the risk of sciatica, highlighting the role of inflammation in its pathogenesis. These findings could inform future research into targeted treatments and enhance our understanding of the biological mechanisms underlying sciatica.

Primary cervical malignant melanoma that was successfully treated with pembrolizumab: a case report and literature review.

Primary malignant melanoma (MM) arising from the cervix is an exceedingly rare occurrence, and patients diagnosed with this condition often face a dismal clinical prognosis. Here, we present a case study of a postmenopausal woman presenting with vaginal bleeding and a conspicuous 5-centimeter black mass on the cervix. Based on the staging criteria established by the International Federation of Gynecology and Obstetrics, she was diagnosed with stage IIB primary cervical MM. The patient underwent neoadjuvant therapy prior to a radical hysterectomy and a bilateral salpingo-oophorectomy. Subsequently, she completed 18 cycles of pembrolizumab therapy, achieving clinical complete remission. Notably, at the 31-month follow-up, there were no signs of recurrence. This successful treatment outcome serves as a valuable clinical reference for the management of primary cervical MM.

The role of B7-H4 in ovarian cancer immunotherapy: current status, challenges, and perspectives.

Immunotherapy stands as a critical and auspicious therapeutic approach in the fight against cancer nowadays. Immune checkpoint inhibitors, in particular, have garnered widespread employment and delivered groundbreaking therapeutic outcomes across various malignancies. However, the efficacy is unsatisfactory in the ovarian cancer. The pressing concerns of the substantial non-response rate require immediate attention. The pursuit of novel targets and the formulation of synergistic combination therapy approaches are imperative for addressing this challenge. B7-H4, a member of the B7 family of co-inhibitory molecules, exhibits high expression levels in ovarian cancer, correlating closely with tumor progression, drug resistance, and unfavorable prognosis. B7-H4 has the potential to serve as a valuable biomarker for evaluating the immune response of patients. Recent investigations and preclinical trials focusing on B7-H4 in the context of ovarian cancer immunotherapy highlight its emergence as a promising immunotherapeutic target. This review aims to discuss these findings and anticipate the future prospects of leveraging B7-H4 in ovarian cancer immunotherapy and targeted therapy.

Clinical and pathological characteristics of cervical clear cell carcinoma in patients not exposed to diethylstilbestrol: a comprehensive analysis of 49 cases.

Purpose: This study aimed to investigate the clinical and pathological characteristics, treatment strategies, and prognosis of cervical clear cell carcinoma (CCCC) in patients not exposed to diethylstilbestrol in utero. Methods: The patients diagnosed with CCCC at West China Second University Hospital of Sichuan University between January 2011 and Jun 2023 were enrolled for this retrospective study. The clinical characteristics and information on treatment and follow-up were collected. The Kaplan-Meier method and Cox regression analysis were performed to identify the relative variables for predicting progression-free survival (PFS) and overall survival (OS). Results: Of the 49 patients included, the Federation International of Gynecology and Obstetrics (FIGO) (2018) stage distribution was 37 (75.5%) stage I, 6 (12.2%) stage II, and 6 (12.2%) stage III. The median follow-up interval was 24.1 months. Six (12.2%) patients had a recurrence, and five (10.2%) patients died. The 5-year PFS rate was 86.8%, and the 5-year OS rate was 88.2%. No recurrence or death was detected in two patients who successfully completed fertility-preserving treatment and seven patients who underwent surgery to preserve ovaries. Two patients became pregnant, giving birth to two babies. The univariate analysis showed that FIGO stage, Pelvic lymph node (PLN) metastasis, lymph vascular space invasion, and depth of stromal invasion (P < 0.05) were significantly associated with PFS and OS. However, no significant prognostic factors were identified in the multivariate analysis. Conclusion: Ovary-preserving treatment and fertility-preserving surgery are safe and feasible in early-stage CCCC. Surveillance other than adjuvant treatment may be a better choice for early-stage CCCC without any pathological risk factors. More targeted therapies and immunotherapy should be pursued in future studies.

Mutation characteristics of cancer susceptibility genes in Chinese ovarian cancer patients.

Introduction: The association between mutations in susceptibility genes and the occurrence of ovarian cancer has been extensively studied. Previous research has primarily concentrated on genes involved in the homologous recombination repair pathway, particularly BRCA1 and BRCA2. However, a wider range of genes related to the DNA damage response pathways has not been fully explored. Methods: To investigate the mutation characteristics of cancer susceptibility genes in the Chinese ovarian cancer population and the associations between gene mutations and clinical data, this study initially gathered a total of 1171 Chinese ovarian cancer samples and compiled a dataset of germline mutations in 171 genes. Results: In this study, it was determined that MC1R and PRKDC were high-frequency ovarian cancer susceptibility genes in the Chinese population, exhibiting notable distinctions from those in European and American populations; moreover high-frequency mutation genes, such as MC1R: c.359T>C and PRKDC: c.10681T>A, typically had high-frequency mutation sites. Furthermore, we identified c.8187G>T as a characteristic mutation of BRCA2 in the Chinese population, and the CHEK2 mutation was significantly associated with the early onset of ovarian cancer, while the CDH1 and FAM175A mutations were more prevalent in Northeast China. Additionally, Fanconi anemia pathway-related genes were significantly associated with ovarian carcinogenesis. Conclusion: In summary, this research provided fundamental data support for the optimization of ovarian cancer gene screening policies and the determination of treatment, and contributed to the precise intervention and management of patients.

PARP inhibitor maintenance treatment for newly diagnosed ovarian cancer patients: a real-world study from China.

Purpose: This study evaluated the efficacy and safety in a real-world population of epithelial ovarian cancer (EOC) treated with poly (ADP-ribose) polymerase inhibitor (PARPi) as first-line maintenance therapy in the largest gynecologic oncology center in Western China. Methods: This study included patients newly diagnosed EOC who received PARPi as first-line maintenance therapy in West China Second University Hospital from August 1, 2018 to September 31, 2022. The primary endpoints were progression-free survival (PFS) and safety evaluated by Common Terminology Criteria for Adverse Events Version 5.0(CTCAE 5.0). The secondary endpoints were overall survival (OS) and prognostic factors influencing the PFS of patients in real world. Results: Among the eligible 164 patients, 104 patients received olaparib and 60 patients received niraparib. 100 patients (61.0%) had mutations in breast cancer susceptibility gene (BRCA). 87 patients (53.0%) received primary debulking surgery (PDS) while 77 patients (47.0%) received interval debulking surgery (IDS). 94 patients (94/164, 57.3%) achieved R0 and 39 patients (23.8%) achieved R1 after PDS/IDS. 112 (68.3%) achieved complete response (CR) after first-line chemotherapy, while 49 (29.9%) achieved partial response (PR). The median follow-up time was 17.0 months (95% CI 15.6-18.4), and the median PFS has not been reached yet. Multivariate analysis demonstrated that BRCA mutations and CR/PR after platinum-based chemotherapy were independent factors associated with prolonged PFS. Hematologic toxicity was the most common grade≥3 AE. There were no incidence of myelodysplastic syndromes/acute myelogenous leukemia (MDS/AML). Conclusion: Focusing on PARPi as first-line maintenance therapy for patients with EOC, this study represented the largest single-center real-world study in China to date. Two independent factors were identified to prolong the PFS of patients: BRCA mutated type and CR/PR after primary treatment, which should be further confirmed with long-term follow-up and large sample sizes.

A lysosome-targeted fluorescent probe based on a BODIPY structure for Cys/Hcy detection.

Cysteine (Cys) and homocysteine (Hcy) are important biothiols in living organisms. They play important roles in a variety of physiological and pathological processes. Therefore, it is very important to design an optical probe for the selective detection of Cys/Hcy. Herein, we report the design and synthesis of a fluorescent probe NBD-B-T based on a boron-dipyrromethene (BODIPY) structure, which showed an excellent lysosome targeting ability and an outstanding Cys/Hcy detection capacity. For NBD-B-T, the sensing group 7-nitro-2,1,3-benzoxadiazole (NBD) and the lysosomal targeting group morpholine were introduced. The results show that the NBD-B-T probe can detect Cys/Hcy with fluorescence emission turn-on performance. The low detection limits of this probe are about 76.0 nM for Hcy and 97.6 nM for Cys, respectively. The NBD-B-T probe has a low detection limit, high stability, and excellent selectivity and sensitivity. More importantly, the NBD-B-T can target lysosome, and simultaneously detect the Cys/Hcy in living cells.

Characteristics of germline DNA damage response gene mutations in ovarian cancer in Southwest China.

DNA damage response (DDR) pathways are responsible for repairing endogenous or exogenous DNA damage to maintain the stability of the cellular genome, including homologous recombination repair (HRR) pathway, mismatch repair (MMR) pathway, etc. In ovarian cancer, current studies are focused on HRR genes, especially BRCA1/2, and the results show regional and population differences. To characterize germline mutations in DDR genes in ovarian cancer in Southwest China, 432 unselected ovarian cancer patients underwent multi-gene panel testing from October 2016 to October 2020. Overall, deleterious germline mutations in DDR genes were detected in 346 patients (80.1%), and in BRCA1/2 were detected in 126 patients (29.2%). The prevalence of deleterious germline mutations in BRCA2 is higher than in other studies (patients are mainly from Eastern China), and so is the mismatch repair genes. We identified three novel BRCA1/2 mutations, two of which probably deleterious (BRCA1 p.K1622* and BRCA2 p.L2987P). Furthermore, we pointed out that deleterious mutations of FNACD2 and RECQL4 are potential ovarian cancer susceptibility genes and may predispose carriers to ovarian cancer. In conclusion, our study highlights the necessity of comprehensive germline mutation detection of DNA damage response genes in ovarian cancer patients, which is conducive to patient management and genetic counseling.

A real-world study of PARP inhibitors in 75 patients with platinum-sensitive recurrent ovarian cancer from China.

Objective: The aim of this study is to assess the efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) as a maintenance therapy for patients with platinum-sensitive recurrent epithelial ovarian cancer (PSROC) at the largest center of gynecologic oncology in Western China. Patients and methods: The efficacy of PARPi was evaluated by progression-free survival (PFS) and overall survival (OS) in this real-world single-center retrospective cohort study conducted at West China Second University Hospital. The safety of PARPi was assessed using Common Terminology Criteria for Adverse Events Version 5.0. Results: In this study, we included a total of 75 eligible patients, of which 54 (72.0%) received olaparib and 21 (28.0%) received niraparib. Among these patients, 24 (32.0%) had breast cancer susceptibility gene (BRCA) mutations, 27 (36.0%) achieved complete response after their last platinum-based therapy, and 22 (29.3%) had previously received ≥3rd-line chemotherapy. The median progression-free survival (mPFS) was 19.1 months (95% CI 8.5-29.7), and the median overall survival (mOS) had not been reached. Log-rank analysis revealed that age (<65 years old V.S. ≥65 years old) and previous lines of chemotherapy (2nd-line V.S. 3rd-line V.S. ≥4th-line) were associated with prolonged PFS (P <0.05). However, multivariate COX regression analysis did not identify any independent factors associated with prognosis (P >0.05). The most common grade≥3 adverse events in the olaparib group were anemia, thrombocytopenia, and leukopenia, while in the niraparib group, they were anemia and thrombocytopenia. Conclusion: This study confirmed that olaparib and niraparib are effective and tolerate for PSROC in real-world settings. At the follow-up endpoint, no independent prognostic factor associated with prolonged PFS was identified.