Building Medication Profiles in the Elderly: a Qualitative Study Based on Medication Information Literacy in a Long-Term Care Facility.

Purpose: Long-term care facilities are increasingly challenged with meeting the diverse healthcare needs of the elderly population, particularly concerning medication management. Understanding medication information literacy and behavior among this demographic is imperative. Therefore, this qualitative study aims to explore medication information literacy and develop distinct medication profiles among elderly long-term care residents. Material and Methods: In this study, we conducted in-depth semi-structured interviews with 32 participants aged 65 or older residing in a long-term care facility. The interviews were designed to explore participants' understanding of medication information, medication management practices, and experiences with healthcare providers. Thematic analysis was employed to analyze the interview data, allowing for the identification of common patterns and themes related to medication-taking behavior among the elderly residents. Results: The thematic analysis revealed four distinct medication behavior profiles among the elderly long-term care residents: (1) Proactive Health Self-Managers, (2) Medication Information Adherents, (3) Experience-Based Medication Users, and (4) Nonadherent Medication Users. These findings provide valuable insights into the diverse approaches to medication management within long-term care facilities and underscore the importance of tailored interventions to support the specific needs of each profile. Conclusion: This study highlights the necessity for tailored medication education and support to optimize medication management for the elderly. With the aging population expansion, addressing the unique medication challenges within long-term care facilities becomes increasingly critical. This research contributes to ongoing endeavors to enhance healthcare services for the elderly, striving for safer and more effective medication-taking behavior.

Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy.

OBJECTIVE: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. METHODS: Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves. RESULTS: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. CONCLUSION: Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Compound Danshen Dripping Pill effectively alleviates cGAS-STING-triggered diseases by disrupting STING-TBK1 interaction.

BACKGROUND: The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (IFN) genes (STING) pathway is critical in the innate immune system and can be mobilized by cytosolic DNA. The various inflammatory and autoimmune diseases progression is highly correlated with aberrant cGAS-STING pathway activation. While some cGAS-STING pathway inhibitor were identified, there are no drugs that can be applied to the clinic. Compound Danshen Dripping Pill (CDDP) has been successfully used in clinic around the world, but the most common application is limited to cardiovascular disease. Therefore, the purpose of the present investigation was to examine whether CDDP inhibits the cGAS-STING pathway and could be used as a therapeutic agent for multiple cGAS-STING-triggered diseases. METHODS: BMDMs, THP1 cells or Trex1-/- BMDMs were stimulated with various cGAS-STING-agonists after pretreatment with CDDP to detect the function of CDDP on IFN-ß and ISGs productionn. Next, we detect the influence on IRF3 and P65 nuclear translocation, STING oligomerization and STING-TBK1-IRF3 complex formation of CDDP. Additionally, the DMXAA-mediated activation mice model of cGAS-STING pathway was used to study the effects of CDDP. Trex1-/- mice model and HFD-mediated obesity model were established to clarify the efficacy of CDDP on inflammatory and autoimmune diseases. RESULTS: CDDP efficacy suppressed the IRF3 phosphorylation or the generation of IFN-ß, ISGs, IL-6 and TNF-α. Mechanistically, CDDP did not influence the STING oligomerization and IRF3-TBK1 and STING-IRF3 interaction, but remarkably eliminated the STING-TBK1 interaction, ultimately blocking the downstream responses. In addition, we also clarified that CDDP could suppress cGAS-STING pathway activation triggered by DMXAA, in vivo. Consistently, CDDP could alleviate multi-organ inflammatory responses in Trex1-/- mice model and attenuate the inflammatory disorders, incleding obesity-induced insulin resistance. CONCLUSION: CDDP is a specifically cGAS-STING pathway inhibitor. Furthermore, we provide novel mechanism for CDDP and discovered a clinical agent for the therapy of cGAS-STING-triggered inflammatory and autoimmune diseases.

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Rebalancing TGF-ß/PGE2 breaks RT-induced immunosuppressive barriers by enhancing tumor-infiltrated dendritic cell homing.

A better understanding of how tumor microenvironments shape immune responses after radiotherapy (RT) is required to improve patient outcomes. This study focuses on the observation that dendritic cells (DCs) infiltrating irradiated cervical tumors are retained in transforming growth factor (TGF)-ß-abundant regions. We report that TGF-ß secretion from cervical cancer cells was increased by irradiation in a dose-dependent manner and that this significantly suppressed the expression of allostimulatory markers and Th1 cytokines in DCs. To investigate further, we blocked the TGF-ß signal in DCs and observed that RT had a dose-dependent immune-promoting effect, improving DC maturation. This suggested that proinflammatory mediators may also be induced by RT, but their effects were being counteracted by the simultaneously increased levels of TGF-ß. Prostaglandin E2 (PGE2), a proinflammatory molecule, was shown to be one such mediator. Adjusting the TGF-ß/PGE2 ratio by inhibiting TGF-ß rebooted RT-induced DC cytoskeletal organization by stimulating myosin light chain (MLC) phosphorylation. Consequently, the homing of intra-tumorally infiltrated DCs to tumor-draining lymph nodes was enhanced, leading to the induction of more robust cytotoxic T cells. Ultimately, rebalancing the TGF-ß/PGE2 ratio amplified the therapeutic effects of RT, resulting in increased intra-tumoral infiltration and activation of CD8+ T cells, and improved tumor control and overall survival rate in mice. DC depletion experiments verified that the improvement in tumor control is directly correlated with the involvement of DCs via the PGE2-MLC pathway. This study emphasizes the importance of maintaining a balanced cytokine environment during RT, particularly hypofractionated RT; and it is advisable to block TGF-ß while preserving PGE2 in the tumor microenvironment in order to better stimulate DC homing and DC -T priming.

Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma.

BACKGROUND: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. METHODS: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. RESULTS: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. CONCLUSIONS: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577).

Liuweiwuling Tablet relieves the inflammatory transformation of hepatocellular carcinoma by inhibiting the PI3K/AKT/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Liuweiwuling Tablet (LWWL) is a patented Chinese medicine approved by the Chinese National Medical Products Administration (NMPA). Clinically, it is used to treat a range of liver diseases that precede hepatocellular carcinoma (HCC), including hepatitis, liver fibrosis and cirrhosis. LWWL is hypothesized to inhibit the inflammatory transformation of HCC, which may have a positive impact on the prevention and treatment of HCC. However, its exact mechanism of action remains unknown. AIM OF THE STUDY: To investigate how LWWL is effective in the treatment of HCC and to validate the pathways involved in this process. MATERIALS AND METHODS: An in vivo model of HCC induced by diethylnitrosamine (DEN) was established to study the effect of LWWL on the development of HCC. The rat serum was analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (γ-GT). The rat liver tissues were stained with hematoxylin and eosin (HE) and Masson's trichrome for pathological analysis. Rat liver tissue was subjected to transcriptome sequencing. Expression of inflammatory and liver fibrosis-related factors in bone marrow-derived macrophages (BMDMs) and LX-2 cells was detected by QRT-PCR, ELISA and Western blot (WB). The expression of apoptosis and stemness genes in HepG2 and Huh7 cells was assessed through flow cytometry and QRT-PCR. Transcriptomics, network pharmacology, WB, and QRT-PCR were employed to validate the mechanisms associated with the amelioration of HCC development by LWWL. RESULTS: LWWL significantly reduced the severity of hepatitis and liver fibrosis, the expression of tumor stemness genes, and the incidence of HCC. In addition, LWWL inhibited the release of inflammatory substances and nuclear accumulation of P65 protein in BMDMs as well as the conversion of LX-2 cells to fibroblasts. LWWL inhibited the proliferation of HepG2 and Huh7 cells, including the initiation of apoptosis and the reduction of stemness gene expression. Importantly, LWWL regulates the PI3K/AKT/NF-κB pathway, which affects hepatic inflammation and cancer progression. CONCLUSION: LWWL inhibited the occurrence and development of HCC by modulating the severity of hepatitis and liver fibrosis, indicating the potential clinical relevance of LWWL in preventing and treating HCC.

Radiation Therapy With Combination Therapy of Immune Checkpoint Inhibitors and Antiangiogenic Therapy for Hepatocellular Carcinoma.

PURPOSE: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have limited efficacy in treating advanced hepatocellular carcinoma (HCC). The synergistic effect of systemic therapy and radiation therapy (RT) might resolve this problem. We aimed to investigate the effect of RT on the treatment outcomes of ICIs and antiangiogenic combination therapy in patients with advanced-stage HCC. METHODS AND MATERIALS: This retrospective observational study analyzed the medical records of 194 patients with Barcelona Clinic Liver Cancer stage C HCC who were admitted to our center from August 2018 to June 2022 and received ICIs combined with antiangiogenic therapy as the first-line treatment. Patients who were administered RT for tumor thrombus or symptomatic metastases within 8 weeks of the commencement of combination therapy were allocated to the RT group, whereas those who did not receive RT were assigned to the non-radiation therapy (NRT) group. Propensity score matching was used to mitigate selection bias. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included objective response rate, disease control rate (DCR), local PFS, out-of-field PFS, and treatment-related adverse events. RESULTS: A total of 76 patients diagnosed with advanced-stage HCC and treated with ICIs and antiangiogenic therapy were included in the study, with 33 patients in the RT group and 43 patients in the non-RT group. After propensity score matching, 29 matched patient pairs were generated. The median follow-up was 15.5 months, and the RT sites were mainly located on the tumor thrombus (55.2%) and extrahepatic metastatic lesions (48.3%). The median PFS was 8.3 months (95% CI, 5.4-11.3) in the RT group and 4.2 months (95% CI, 3.4-5.0) in the NRT group (P < .001). The median OS was not reached in the RT group and was 9.7 months (95% CI, 4.1-15.3) in the NRT group (P = .002). The objective response rate was 75.9% (95% CI, 56.5-89.7) in the RT group and 24.1% (95% CI, 10.3-43.5) in the NRT group (P < .001). The DCR was 100% in the RT group and 75.9% (95% CI, 56.5-89.7) in the NRT group (P = .005). The median local PFS and out-of-field PFS were 13.2 months (95% CI, 6.3-20.1) and 10.8 months (95% CI, 7.0-14.7), respectively. RT was an independent prognostic factor for PFS (hazard ratio = 0.33; 95% CI, 0.17-0.64; P < .001) and OS (hazard ratio = 0.28; 95% CI, 0.11-0.68; P = .005), respectively. The rates of any grade treatment-related adverse events were similar between the 2 groups. CONCLUSIONS: In comparison to the combination of ICIs and antiangiogenic therapy, the inclusion of RT has been observed to improve the DCR and survival outcomes in patients with advanced-stage HCC. The safety profile of this triple therapy was satisfactory.

Efficacy and safety of subsequent radiotherapy in patients with advanced-stage hepatocellular carcinoma treated with immune checkpoint inhibitors.

Background: The development of immunotherapy resistance is associated with a poor prognosis in patients diagnosed with hepatocellular carcinoma (HCC) who are undergoing treatment with immune checkpoint inhibitors (ICI). This study aimed to evaluate the efficacy and safety of subsequent radiotherapy (RT) for patients with advanced-stage HCC who had lesion enlargement or new lesions (NLs) during ICI therapy. Methods: This retrospective observational study enrolled 36 patients with advanced-stage HCC who underwent subsequent RT for lesion enlargement or NLs during ICI therapy from two centers. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), 1- and 2-year local control (LC) rates, in-field PFS (IFPFS), out-field PFS (OFPFS), and safety. Results: The median follow-up time was 15.3 months. The median PFS was 7.4 months [95% confidence interval (CI): 3.1-11.7 months], and the median OS was 18.8 months (95% CI: 17.1-20.5 months). ORR and DCR were 38.9% and 72.2%, respectively. In addition, the median IFPFS was 17.8 months (95% CI: 11.5-24.2 months), median OFPFS was 7.9 months (95% CI: 3.4-12.5 months), and estimated 1- and 2-year LC rates were 67.1% and 31.9%, respectively. The most common treatment-related adverse events (all grades) were diarrhea (33.3%), rash (30.6%), and malaise (27.8%); a total of 14 (38.9%) patients developed grade 3-4 AEs. Conclusions: Subsequent RT showed reliable antitumor effects and an acceptable safety profile in patients with advanced-stage HCC who had unsatisfactory response to ICI therapy; therefore, it could serve as an optional salvage strategy.

Risk Factors for Nodal Failure in Patients with FIGO IIIC Cervical Cancer Receiving Definitive Image-Guided Radiotherapy.

BACKGROUND: Nodal failure is a major failure pattern for patients with FIGO IIIC cervical cancer, which is further associated with worse survival. This study was designed to investigate risk factors for nodal failure in FIGO IIIC cervical cancer patients. METHODS: The characteristics of positive lymph nodes (LNs) and relevant clinical factors of 162 FIGO IIIC cervical cancer patients were collected. The chi-square test and logistic regression model were used to identify risk factors for nodal failure. RESULTS: In total, 368 positive LNs were identified, including 307 pelvic LNs and 61 para-aortic LNs. The nodal failure rates for all LNs, pelvic LNs, and para-aortic LNs were 9.2%, 7.8%, and 16.4%, respectively. After 20 fractions of RT, a nodal short diameter (D20F) ≥ 0.95 cm and a ratio of nodal shrinkage (ΔV20F) < 0.435 resulted; <4 cycles of chemotherapy indicated higher nodal failure rates for all LNs. For pelvic LNs, ΔV20F < 0.435 and <4 cycles of chemotherapy were associated with a higher incidence of nodal failure. For para-aortic LNs, ΔV20F < 0.435 was the only risk factor for nodal failure. CONCLUSIONS: Para-aortic LNs were more likely to experience nodal failure than pelvic LNs. Nodal shrinkage during radiotherapy and cycles of chemotherapy were associated with nodal failure in patients with FIGO IIIC cervical cancer.

Quality assurance in a phase III, multicenter, randomized trial of POstmastectomy radioThErapy in Node posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a planning benchmark case.

PURPOSE: To report the planning benchmark case results of the POTENTIAL trial-a multicenter, randomized, phase 3 trial-to evaluate the value of internal mammary nodal (IMN) irradiation for patients with high-risk breast cancer. METHODS: All participating institutions were provided the outlines of one benchmark case, and they generated radiation therapy plans per protocol. The plans were evaluated by a quality assurance team, after which the institutions resubmitted their revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed in the first and final submission. RESULTS: The plans from 26 institutions were analyzed. Some major deviations were found in the first submission. The protocol compliance rates of dose coverage for the planning target volume of chest wall, supraclavicular fossa plus axilla, and IMN region (PTVim) were all significantly improved in the final submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8%, respectively. For OARs, the compliance rates of heart Dmean, left anterior descending coronary artery V40Gy, ipsilateral lung V5Gy, and stomach V5Gy were significantly improved. In the first and final submission, the mean values of PTVim V100% were 79.9% vs. 92.7%; the mean values of heart Dmean were 11.5 Gy vs. 9.7 Gy for hypofractionated radiation therapy and 11.5 Gy vs. 11.0 Gy for conventional fractionated radiation therapy, respectively. CONCLUSION: The major deviations were corrected and protocol compliance was significantly improved after revision, which highlighted the importance of planning benchmark case to guarantee the planning quality for multicenter trials.

Developing a Quality Evaluation Index System for E-Consultation Doctor-Patient Communication Using the Delphi Method.

Background: E-consultation medical services have become popular globally, which offers patients more options, regardless of time or location. However, research indicates a prevalent issue with the communication quality in e-consultations, leading to sub-optimal patient experiences. Objective: This study aims to design an evaluation system for e-consultation quality. The developed scale guides operators in improving services and users in assessing their experience. It aids in selecting e-consultation services, saving costs, and assisting doctors in making informed decisions. Methods: This study combines existing scales, literature analysis, and expert consultation to form preliminary evaluation indicators. Fourteen experts were invited using stratified purposive sampling. Two rounds of Delphi method were conducted to exclude indicators that did not meet basic conditions. The final evaluation system was determined through expert discussions and revisions. The Analytic Hierarchy Process (AHP) quantified indicator weights. Results: Both rounds of the questionnaire saw compelling response rates of 100% (14 out of 14) and 92.86% (13 out of 14), respectively. Meanwhile, the Expert Authority Coefficient (Cr) was recorded at 0.89 and 0.88, respectively, while the Kendall Consistency Coefficient (Kendall W) for all level indicators fluctuated between 0.133 and 0.37 (P<0.05). The ultimate indicator system formulated includes three primary indicators, ten secondary indicators, and thirty-two tertiary indicators. The highest to lowest weighted first-level indicators were 'Joint Decision-Making between Doctors and Patients' (0.6232), 'Patient Responsiveness' (0.2395), and "Interpersonal Relationship between Doctors and Patients" (0.1373). Weights for the second-level and third-level indicators were also determined. Conclusion: A scientific scale for e-consultation quality evaluation has been created, which effectively captures the essence of online medical communication and patient experiences. It enriches the theoretical framework for evaluating e-consultation quality, broadens perspectives in Internet medicine, provides practical guidance for network medical service managers and users and the development of the "Internet + medical health" service model.

Icariside I reduces breast cancer proliferation, apoptosis, invasion, and metastasis probably through inhibiting IL-6/STAT3 signaling pathway.

OBJECTIVES: Breast cancer is a common malignancy in women. More than 90% of breast cancer deaths are caused by metastasis. Epimedii Folium (EF) is a commonly used herb with anti-tumor benefits, but its underlying mechanisms and active components for breast cancer prevention are little understood. This study assessed the therapeutic role of Icariside I (ICS I) in Epimedium flavonoids (EF) on lung metastasis of breast cancer, including the underlying mechanism. METHODS: Western blot, RT-qPCR, wound healing assay, colony formation assay, and flow cytometry were used to investigate the inhibition of breast cancer cells growth and migration by EF and ICS I through disrupting the IL-6/STAT3 pathway. Combined with 4T1 breast cancer model in mice, Western blot, RT-qPCR, Hematoxylin and Eosin staining, immunohistochemistry were used to evaluate the therapeutic role of ICS I in proliferation, apoptosis, invasion, and metastasis of breast cancer. KEY FINDINGS: EF can inhibit STAT3 phosphorylation and reduce the colony formation and migration of breast cancer cells. Detecting the active ingredients in EF, we found ICS I can reduce the activation of STAT3 in 4T1 breast cancer cells, impair colony formation and migration. Moreover, ICS I induced cells G1 phase arrest and modulated Cyclin D1, CDK4, bcl-2, and bax to inhibit proliferation and survival of breast cancer cells. Similarly, the in vivo studies demonstrated that ICS I significantly suppressed tumor development and lung metastasis in the 4T1 mouse model. Tumor cells in vehicle group were arranged in a spoke-like pattern with obvious heterogeneity, and multinucleated tumor giant cells were seen. But, the tumor cells in the ICS I group were disorganized and necrotic lysis was seen in some areas. In ICS I-treated group, tumors' STAT3 phosphorylation level, IL-6, Cyclin D1, CDK4, bcl-2, and vimentin expression were downregulated, bax and cleaved caspase 3 expression were upregulated. In the lung tissue, we could find less metastasis of breast cancer cells and less lung injury in the ICS I group. Besides, the expression of metastasis-related genes MMP9 and vimentin was decreased in the lung tissue of ICS I group. CONCLUSIONS: These findings suggest that ICS I can inhibit breast cancer proliferation, apoptosis, invasion and metastasis probably via targeting IL-6/STAT3 pathway. Therefore, ICS I has the potential to become an innovative therapeutic candidate to breast cancer prevention and treatment.

Psychological Health and Risk Factors of College Students within the Context of the COVID-19 Pandemic: A Cross-Sectional Study.

BACKGROUND: Students are a priority population in mental health research. This study aimed to explore the risk factors of anxiety and depression symptoms among college students in Chongqing, a megacity under the impact of COVID-19, and to provide a basis for determining the priorities of public health policies and implementing effective educational health care interventions. METHODS: In this cross-sectional study conducted in Chongqing, China, the data came from web-based stratified random sampling. Anxiety and depression symptoms were measured by the Self-Rating Anxiety Scale (SAS) and the Center for Epidemiological Studies Depression Scale (CES-D), respectively, and risk factors were analyzed by logistic regression. RESULTS: Data were obtained from 915 college students (34.75% were male, and 65.25% were female) with age (20.29 ± 1.51) in Chongqing, China. The prevalence rates of anxiety and depression were 19.78% and 22.62%, respectively. Logistic regression analysis revealed that the risk factors of anxiety symptoms were associated with junior years, sleep time of less than 6 h a day, influence on career planning, and depression symptoms. Comprehensive, science and engineering, and medicine disciplines, having siblings, poorer mastery of study, and anxiety symptoms were risk factors for developing depression symptoms. CONCLUSIONS: During the pandemic, college students experienced varying degrees of anxiety and depression. Our research findings highlight the necessity of universities and relevant departments providing precise mental health education for college students under major public health emergencies.

Intensity-modulated radiotherapy for cushing's disease: single-center experience in 70 patients.

Context: Intensity-modulated radiotherapy (IMRT) is a modern precision radiotherapy technique for the treatment of the pituitary adenoma. Objective: Aim to investigate the efficacy and toxicity of IMRT in treating Cushing's Disease (CD). Methods: 70 of 115 patients with CD treated with IMRT at our institute from April 2012 to August 2021 were included in the study. The radiation doses were usually 45-50 Gy in 25 fractions. After IMRT, endocrine evaluations were performed every 6 months and magnetic resonance imaging (MRI) annually. Endocrine remission was defined as suppression of 1 mg dexamethasone test (DST) or normal 24-hour urinary free cortisol level (24hUFC). The outcome of endocrine remission, endocrine recurrence, tumor control and complications were retrieved from medical record. Results: At a median follow-up time of 36.8 months, the endocrine remission rate at 1, 2, 3 and 5 years were 28.5%, 50.2%, 62.5% and 74.0%, respectively. The median time to remission was 24 months (95%CI: 14.0-34.0). Endocrine recurrence was found in 5 patients (13.5%) till the last follow-up. The recurrence-free rate at 1, 2, 3 and 5 years after endocrine remission was 98.2%, 93.9%, 88.7% and 88.7%, respectively. The tumor control rate was 98%. The overall incidence of new onset hypopituitarism was 22.9%, with hypothyroidism serving as the most common individual axis deficiency. Univariate analysis indicated that only higher Ki-67 index (P=0.044) was significant favorable factors for endocrine remission. Conclusion: IMRT was a highly effective second-line therapy with low side effect profile for CD patients. Endocrine remission, tumor control and recurrence rates were comparable to previous reports on FRT and SRS.

The application of 3D brachytherapy in cervical stump cancer: A retrospective study.

Purpose: Cervical stump cancer is a carcinoma that grows on the cervical stump after a sub-total hysterectomy. There have been no studies on the application of 3D brachytherapy in cervical stump cancer. In the present study, we aimed to compare the curative effects, toxicity, and dosimetry of 3D and 2D brachytherapy in cervical stump cancer. Material and methods: Thirty-one patients admitted between 2012 and 2021, who were concurrently treated with intensity-modulated radiation therapy and brachytherapy for cervical stump cancer were divided into three groups according to the brachytherapy techniques: 2D brachytherapy, 3D image-guided brachytherapy (3D-IGBT), and 2D + 3D. For patients undergoing 2D brachytherapy and 3D-IGBT, data on survival, complications, and dose to target area or organs at risk (OARs) were collected and compared. Furthermore, dosimetry difference was investigated by reconstructing the 2D plan into a 3D plan. Results: The median follow-up duration of all patients was 58 months. The overall 5-year progression-free survival, overall survival, and local control rates were 69.6%, 90.2%, and 78.2%, respectively. Late complications in the rectum, sigmoid colon, and bladder were milder in 3D brachytherapy than in 2D brachytherapy. Concerning the D90 value of clinical target volume (CTV) and D2cm3 value of OARs in EQD2, the 3D brachytherapy provided a lower dose to CTV (76.5 Gy vs. 95.9 Gy, on average) and OARs compared with 2D brachytherapy. Conclusions: Despite lacking statistical significance, 3D brachytherapy showed better outcomes regarding late toxicity than 2D brachytherapy, owing to the lower dose coverage in the bladder, rectum, sigmoid colon, and small intestine.

Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China.

BACKGROUND: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. METHODS: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). RESULTS: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3-5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. CONCLUSION: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. TRIAL REGISTRATION: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).

Radiotherapy for postoperative vaginal recurrences of cervical squamous cell carcinoma: analysis of dosing and prognosis.

Squamous cell carcinoma (SCC) is the most common type of vaginal recurrence in cervical cancer patients, and the role of salvage radiotherapy on these patients remains unclear. This study aimed to investigate the efficacy of salvage radiotherapy for vaginal recurrence of SCC in patients who previously underwent surgery and to explore prognostic factors associated with survival. Ninety-seven patients with histologically proven SCC who were treated for vaginal recurrence at Peking Union Medical College Hospital were identified. All patients had previously undergone surgery and received salvage radiotherapy. Factors predictive of overall survival (OS), progression-free survival (PFS), and local control (LC) were investigated. The median follow-up time was 42.5 months. The estimated 5-year OS, PFS, and LC rates were 84%, 79%, and 91%. On multivariate analysis, inguinal lymph node metastasis was significantly associated with poor OS; a tumour size ≤4 cm was associated with longer PFS (p < 0.05); the recurrence pattern was an independent predictor of LC (p < 0.05). In the 45 patients with recurrences that were paravaginal or invasive of surrounding organs, biologically equivalent doses in 2 Gy fractions of ≥72.6 Gy were independently predictive of longer LC (p < 0.05). RT is an effective treatment for postoperative vaginal recurrence in patients with cervical SCC. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal.Impact statementWhat is already known on this subject? Radiotherapy plays a critical role in treating recurrent cervical cancer, but the effectiveness of RT for vaginal recurrence in patients who previously underwent surgery remains limited. Few studies have focussed on the effect of RT dose on patient survival.What do the results of this study add? This study investigated the efficacy of RT in patients with cervical squamous cell carcinoma who experienced postoperative recurrence. Lymph node metastasis, tumour size and recurrence pattern were significantly associated with survival. Moreover, an EQD2 ≥ 72.6 Gy was independently predictive of longer LC.What are the implications of these findings for clinical practice and/or further research? RT is an effective treatment for postoperative vaginal recurrence in patients with cervical squamous cell carcinoma. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal.

Tanshinone I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC.

BACKGROUND: Abnormal activation of NLRP3 inflammasome is related to a series of inflammatory diseases, including type 2 diabetes, gouty arthritis, non-alcoholic steatohepatitis (NASH), and neurodegenerative disorders. Therefore, targeting NLRP3 inflammasome is regarded as a potential therapeutic strategy for many inflammatory diseases. A growing number of studies have identified tanshinone I (Tan I) as a potential anti-inflammatory agent because of its good anti-inflammatory activity. However, its specific anti-inflammatory mechanism and direct target are unclear and need further study. METHODS: IL-1ß and caspase-1 were detected by immunoblotting and ELISA, and mtROS levels were measured by flow cytometry. Immunoprecipitation was used to explore the interaction between NLRP3, NEK7 and ASC. In a mouse model of LPS-induced septic shock, IL-1ß levels in peritoneal lavage fluid and serum were measured by ELISA. Liver inflammation and fibrosis in the NASH model were analyzed by HE staining and immunohistochemistry. RESULTS: Tan I inhibited the activation of NLRP3 inflammasome in macrophages, but had no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, Tan I inhibited NLRP3 inflammasome assembly and activation by targeting NLRP3-ASC interaction. Furthermore, Tan I exhibited protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including septic shock and NASH. CONCLUSIONS: Tan I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC, and exhibits protective effects in mouse models of LPS-induced septic shock and NASH. These findings suggest that Tan I is a specific NLRP3 inhibitor and may be a promising candidate for treating NLRP3 inflammasome-related diseases.

Postoperative adjuvant radiotherapy for patients with upper tract urothelial carcinoma (UTUC) who underwent kidney-sparing surgery (KSS): a single-center study.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of postoperative adjuvant radiotherapy for patients with upper tract urothelial carcinoma (UTUC) who underwent kidney-sparing surgery (KSS). METHODS: We retrospectively reviewed the clinical records of 31 patients with primary UTUC who underwent kidney-sparing surgery (KSS) and who were treated with adjuvant radiotherapy at our center between October 1998 and May 2017. Statistical analyses were performed with SPSS 23.0. The primary endpoints of this study included overall survival (OS) and local recurrence-free survival (LRFS); the secondary endpoints were disease-free survival (DFS) and treatment-related toxicity. RESULTS: The median follow-up was 58.4 months (range, 12.7-185.3 months), and the median local recurrence time was 59.0 months (range, 7.0-185 months). All of the patients completed radiotherapy on schedule, and no grade 3-4 late-stage reaction was observed. The estimated 5-year and 10-year OS, DFS and LRFS rates of the patients were 64.0%, 61.1%, 69.6% and 48.0%, 40.9%, 64.6%, respectively. Univariate analysis showed that age (χ2 = 4.224, P = 0.040), R0 resection (χ2 = 3.949, P = 0.047), and early stage (I + II) (χ2 = 6.515, P = 0.011) were associated with good OS; DFS benefit in early stage patients (χ2 = 6.151, P = 0.013) and age<70 years old (χ2 = 5.091, P = 0.024). Patients with distal ureteral segments had better LRFS than patients with proximal ureteral cancer (χ2 = 5.248, P = 0.022). However, multivariate analysis showed that age was the only factor of OS (χ2 = 4.099, P = 0.043). CONCLUSION: Adjuvant radiotherapy is safe and tolerated, and LRFS was superior in middle and distal ureteral cancer than in proximal ureteral cancer.