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Abstract Background In patients undergoing breast-conserving therapy without surgical clip implantation, the accuracy of tumor bed identification and the consistency of clinical target volume (CTV) delineation under computed tomography (CT) simulation remain suboptimal. This study aimed to investigate the feasibility of implementing preoperative magnetic resonance (MR) simulation on delineations by assessing interobserver variability (IOV). Methods Preoperative MR and postoperative CT simulations were performed in patients who underwent breast-conserving surgery with no surgical clips implanted. Custom immobilization pads were used to ensure the same supine position. Three radiation oncologists independently delineated the CTV of tumor bed on the images acquired from MR and CT simulation registration and CT simulation alone. Cavity visualization score (CVS) was assigned to each patient based on the clarity of the tumor bed on CT simulation images. IOV was indicated by generalized conformity index (CIgen), denoted as CIgen−CT and CIgen−MR/CT, and the distance between the centroid of mass (dCOM), denoted as dCOMCT and dCOMMR/CT. The variation of IOV in different CVS subgroups was analyzed. Results A total of 10 patients were enrolled in this study. The median and interquartile range (IQR) of maximum pathological diameter of the tumors in all patients were 1.55 (0.80–1.92) cm. No statistical significance was found between the volumes of CTVs on CT simulation and on MR/CT simulation registration images (p = 0.387). CIgen−MR/CT was significantly larger than CIgen−CT (p = 0.005). dCOMMR/CT was significantly smaller than dCOMCT (p = 0.037). The median and IQR of CVS in all patients were 2.34 (2.00–3.08). The difference of CIgen between CIgen−MR/CT and CIgen−CT was larger in the low CVS group (p = 0.016). The difference of dCOM showed a decreasing trend when CVS was lower, although it did not reach statistical significance (p = 0.095). Conclusions For patients who underwent breast-conserving surgery without surgical clip implantation, the use of preoperative MR simulation in delineating the CTV of tumor bed decreased the IOV among observers. The consistency of tumor bed identification was improved especially in cases where the margins of tumor bed were challenging to visualize on CT simulation images. The study findings offer potential benefits in reducing local recurrence and minimizing tissue irritation in the surrounding areas. Future investigation in a larger patient cohort to validate our results is warranted.

Abstract Objectives This study evaluates the efficacy and toxicity of image-guided brachytherapy combined with or without external beam radiotherapy (IGBT ± EBRT) as definitive treatment for patients with inoperable endometrial cancer (IOEC), in addition to establishing a risk classification to predict prognosis. Methods Fifty-one IOEC patients who underwent IGBT ± EBRT at Peking Union Medical College Hospital from January 2012 to December 2021 were retrospectively analyzed, of which 42 patients (82.4%) were treated with IGBT + EBRT and 9 patients (17.6%) with IGBT alone. Establishing risk classification based on FIGO 2009 staging and biopsy pathology, stage III/IV, non-endometrioid, or Grade 3 endometrioid cancer were included in the high-risk group (n = 25), and stage I/II with Grade 1–2 endometrioid cancer was included in the low-risk group (n = 26). Results The median follow-up time was 58.0 months (IQR, 37.0–69.0). Clinical complete remission (CR) was achieved in 92.2% of patients after radiotherapy (n = 47). The cumulative incidences of locoregional and distant failure were 19.6% (n = 10) and 7.8% (n = 4), respectively. A total of 20 patients died (39.2%), including 10 cancer-related deaths (19.6%) and 10 comorbidity-related deaths (19.6%). The 5-year locoregional control (LRC), time to progression (TTP), overall survival (OS), and cancer-specific survival (CSS) were 76.9%, 71.2%, 59.4%, and 77.0%, respectively. No Grade 3 or above acute or late toxicities were reported. In univariate analysis, LRC, TTP, and CSS were significantly higher in the low-risk group than in the high-risk group (P

Abstract Background Squama Manis is a valuable traditional Chinese medicine with a long history of medicinal use in the treatment of breast-related diseases. However, owing to the excessive exploitation and utilization of the resources, Squama Manis has been included in the list of rare and endangered wild animals. The conservation of the resources of Squama Manis and continuing its clinical application has become an urgent problem, and the search for small-molecule substitutes for Squama Manis is an effective way to achieve this goal. Previous studies have identified PA3264 as a possible active ingredient in Squama Manis. In this study, we systematically investigated the pharmacological effects and mechanisms of PA3264 in the treatment of triple-negative breast cancer (TNBC), a representative breast-related disease. Methods Cell viability and colony formation assays were performed after treatment with the target dipeptide PA3264 in vitro. Next, 4T1 orthotopic tumors and humanized PBMC-CDX mouse models were generated to examine the antitumor effect of PA3264 in vivo. Transcriptome sequencing and molecular docking experiments were performed to predict pathways to function. Western blotting and quantitative real-time PCR were used to validate the molecular mechanisms underlying the anticancer effects of PA3264. Results PA3264 significantly inhibited cell viability and migration of breast cancer cells in vitro. Furthermore, PA3264 suppressed the tumor size and reduced the tumor weight in vivo. Finally, it was verified that PA3264 prevented the progression of breast cancer by inhibiting the PI3K/AKT/NF-κB pathway, causing cell cycle arrest, and promoting apoptosis. Conclusions This study elucidated that PA3264 derived from rare and endangered Squama Manis was a novel bioactive peptide for treating triple-negative breast cancer from a scientific research perspective.

Abstract Background The safety of medication use among older adults is a growing concern, given the aging population. Despite widespread attention, the exploration of medication literacy in older adults, particularly from the perspective of information literacy, is in its nascent stages. Methods This study utilized the existing literature to define medication information literacy (MIL) as a theoretical framework. A two‐round Delphi survey was conducted to identify the essential components of a MIL indicator system for older adults. The analytic hierarchy process (AHP) was then used to assign weights to each indicator. Results The study observed relatively high response rates in both rounds of the questionnaire, which, along with expert authority coefficients (Cr) of 0.86 and 0.89, underscores the credibility and expertise of the panellists. Additionally, Kendall's coefficient of concordance (Kendall's W) ranging from 0.157 to 0.33 (p

With the advancing comprehension of immunology, an increasing number of immunotherapies are being explored and implemented in the field of cancer treatment. The cGAS-STING pathway, a crucial element of the innate immune response, has been identified as pivotal in cancer immunotherapy. We evaluated the antitumor effects of Schisandra chinensis lignan component Schisandrin C (SC) in 4T1 and MC38 tumor-bearing mice, and studied the enhancing effects of SC on the cGAS-STING pathway and antitumor immunity through RNA sequencing, qRT-PCR, and flow cytometry. Our findings revealed that SC significantly inhibited tumor growth in models of both breast and colon cancer. This suppression of tumor growth was attributed to the activation of type I IFN response and the augmented presence of T cells and NK cells within the tumor. Additionally, SC markedly promoted the cGAS-STING pathway activation induced by cisplatin. In comparison to cisplatin monotherapy, the combined treatment of SC and cisplatin exhibited a greater inhibitory effect on tumor growth. The amplified chemotherapeutic efficacy was associated with an enhanced type I IFN response and strengthened antitumor immunity. SC was shown to reduce tumor growth and increase chemotherapy sensitivity by enhancing the type I IFN response activation and boosting antitumor immunity, which enriched the research into the antitumor immunity of S. chinensis and laid a theoretical basis for its application in combating breast and colon cancer.

Abstract 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.

Abstract 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

Background For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the therapeutic efficacy and toxicity of postoperative radiotherapy to the abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients, who had all received surgery and chemotherapy (CT). Methods We retrospectively collected patients with stage III epithelial ovarian cancer after cytoreductive surgery (CRS) and full-course adjuvant CT. The chemoradiotherapy (CRT) group patients were treated with intensity modulated radiotherapy (IMRT) to the abdominal and pelvic lymphatic drainage area in our hospital between 2010 and 2020. A propensity score matching analysis was conducted to compare the results between the CRT and CT groups. Kaplan-Meier analysis estimated overall survival (OS), disease-free survival (DFS), and local control (LC) rates. The log-rank test determined the significance of prognostic factors. Results A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CRT and RT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumour, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median DFS time, 5-year OS, and local recurrence free survival (LRFS) were 100.0 months vs 25.9 months ( P = .020), 69.2% vs 49.9% ( P = .002), and 85.9% vs 50.5% ( P = .020), respectively. The CRT group mainly presented with acute haematological toxicities, with no statistically significant difference compared with grade III intestinal adverse effects (3/44 vs 6/88, P = .480). Conclusion This report demonstrates that long-term DFS could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to the abdominal and pelvic lymphatic area. Compared with the CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.

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; 20F < 0.435 and 20F < 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.

Abstract Objective To investigate the clinical outcomes and recurrence patterns of high‐intermediate‐risk (HIR)‐ and high‐risk (HR) early‐stage endometrial cancer (EC) treated with postoperative intracavitary brachytherapy alone. Methods We included 152 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I‐II endometrial cancer with HIR and HR factors who received vaginal brachytherapy alone after surgery in our center between April 2008 and December 2017. The irradiation area was the top and upper halves of the vagina. The reference point was defined as 0.5 cm below the vaginal mucosa. The radiation dose was 25–30 Gy 5–6 times. The Kaplan–Meier method was used to calculate the survival rate; differences were assessed using the log‐rank test, and univariate and multivariate prognostic analyses were performed using the Cox regression model. Result The median follow‐up was 49.2 months (range 3–132 months). The 5‐year overall survival (OS), disease‐free survival (DFS), locoregional failure‐free survival time (LRFS), and distant metastasis‐free survival (DMFS) rates were 93.2%, 83.4%, 87.9%, and 86.6%, respectively. Treatment failure occurred in 18 patients, locoregional recurrence in 11, and distant metastasis in 14 (four with locoregional recurrence). Distant metastasis is the main recurrence pattern in patients at HIR and HR. Univariate and multivariate analyses revealed that age was an independent prognostic factor for OS, DFS, DMFS, and LRFS. Conclusion The main recurrence pattern after adjuvant vaginal brachytherapy alone was distant metastasis in patients with HIR and HR early‐stage EC. Age at onset was an independent prognostic factor for survival. Vaginal brachytherapy alone is an acceptable treatment option for patients with HIR and HR early‐stage endometrial cancer.

Abstract 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).

Abstract 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

Abstract 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-1β 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-1β 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. Graphical Abstract

Abstract Background Radiotherapy standardized training (ST) has been conducted for 7 years in China. This investigation evaluated the difficulties of and need for ST of radiation oncology residents (RORs) for gynaecological tumours (GYN) in China. Methods An anonymous online survey was conducted on the “Questionnaire Star” platform. The questionnaire contained 30 questions, including the basic information of the students, their knowledge of radiotherapy theory, training on GYN, the difficulties and needs they faced, and possible solutions. Results A total of 469 valid questionnaires were collected, resulting in a valid response rate of 85.3%. During the ST, only 58–60% of RORs received training in GYN, with a median clinical rotation time of 2–3 months. Among the RORs surveyed, 50.1% knew the physical characteristics of brachytherapy (BRT), and 49.2% could choose the appropriate BRT for patients. At the end of ST, 75.3% were able to complete the target delineation in GYN independently, and 56% were able to complete the BRT operation independently. The scarcity of GYN patients, insufficient teaching awareness of superior doctors, and lack of interest are the main reasons why ST cannot meet the standard. Conclusion In China, the ST of RORs in GYN should be strengthened, the teaching awareness of specialist trainers should be increased, and the curriculum should be optimized, especially the curriculum for specialist operation and a strict assessment system.

Abstract Background Food safety is of global importance and has been of concern in university settings in recent years. However, effective methods to conduct food safety education are limited. This study aims to evaluate the effects of an intervention on food safety knowledge, attitudes and practices (KAP) by social media, WeChat, among university students. Methods A quasi-experimental study was conducted in Chongqing, China. Two departments were recruited randomly from a normal university and a medical university. One department from each university was randomly selected as the intervention group and the other as the control group. All freshmen students in each selected department were chosen to participate in this study. One thousand and twenty-three students were included at baseline, and 444 students completed the study. This intervention was conducted through food safety-related popular science articles with an average of three articles per week released by WeChat official accounts called "Yingyangren" for two months to the intervention group. No intervention was conducted in the control group. An independent t-test was used to test statistical differences in the food safety KAP scores between the two groups. A paired t-test was used to test statistical differences in the food safety KAP scores between before and after the intervention. And quantile regression analysis was conducted to explore the difference between the two groups across the quantile levels of KAP change. Results After the intervention, compared with control group, participants in the intervention group did not score significant higher on knowledge (p = 0.98), attitude (p = 0.13), and practice (p = 0.21). And the scores of food safety knowledge and practices slightly improved after the intervention both in the intervention group (p = 0.01 and p = 0.01, respectively) and in the control group (p = 0.0003 and p = 0.0001, respectively). Additionally, the quantile regression analysis showed that the intervention had no effect on improving the food safety KAP scores. Conclusions The intervention using the WeChat official account had limited effects on improving the food safety KAP among the university students. This study was an exploration of food safety intervention using the WeChat official account; valuable experience can be provided for social media intervention in future study. Trial registration ChiCTR-OCH-14004861.

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

Context Schisandra chinensis (Turcz.) Baill. (Magnoliaceae) essential oil (SCEO) composition is rich in lignans that are believed to perform protective effects in the liver.Objective This study investigates the effects of SCEO in the treatment of acetaminophen (APAP)-induced liver injury in mice.Materials and methods C57BL/6 mice (n = 56) were randomly divided into seven groups: normal; APAP (300 mg/kg); APAP plus bicyclol (200 mg/kg); APAP plus SCEO (0.25, 0.5, 1, 2 g/kg). Serum biochemical parameters for liver function, inflammatory factors, and antioxidant activities were determined. The protein expression levels of Nrf2, GCLC, GCLM, HO-1, p62, and LC3 were assessed by western blotting. Nrf2, GCLC, HO-1, p62, and LC3 mRNA were detected by real-time PCR.Results Compared to APAP overdose, SCEO (2 g/kg) pre-treatment reduced the serum levels of AST (79.4%), ALT (84.6%), TNF-α (57.3%), and IL-6 (53.0%). In addition, SCEO (2 g/kg) markedly suppressed cytochrome P450 2E1 (CYP2E1) (15.4%) and attenuated the exhaustion of GSH (43.6%) and SOD (16.8%), and the accumulation of MDA (22.6%) in the liver, to inhibit the occurrence of oxidative stress. Moreover, hepatic tissues from our experiment revealed that SCEO pre-treatment mitigated liver injury caused by oxidative stress by increasing Nrf2, HO-1, and GCL. Additionally, SCEO activated autophagy, which upregulated hepatic LC3-II and decreased p62 in APAP overdose mice (p

Abstract Background Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease that affects neurons in the central nervous system and the spinal cord. As in many other neurodegenerative disorders, the genetic risk factors and pathogenesis of ALS involve dysregulation of cytoskeleton and neuronal transport. Notably, sensory and motor neuron diseases such as hereditary sensory and autonomic neuropathy type 2 (HSAN2) and spastic paraplegia 30 (SPG30) share several causative genes with ALS, as well as having common clinical phenotypes. KIF1A encodes a kinesin 3 motor that transports presynaptic vesicle precursors (SVPs) and dense core vesicles and has been reported as a causative gene for HSAN2 and SPG30. Methods Here, we analyzed whole-exome sequencing data from 941 patients with ALS to investigate the genetic association of KIF1A with ALS. Results We identified rare damage variants (RDVs) in the KIF1A gene associated with ALS and delineated the clinical characteristics of ALS patients with KIF1A RDVs. Clinically, these patients tended to exhibit sensory disturbance. Interestingly, the majority of these variants are located at the C-terminal cargo-binding region of the KIF1A protein. Functional examination revealed that the ALS-associated KIF1A variants located in the C-terminal region preferentially enhanced the binding of SVPs containing RAB3A, VAMP2, and synaptophysin. Expression of several disease-related KIF1A mutants in cultured mouse cortical neurons led to enhanced colocalization of RAB3A or VAMP2 with the KIF1A motor. Conclusions Our study highlighted the importance of KIF1A motor-mediated transport in the pathogenesis of ALS, indicating KIF1A as an important player in the oligogenic scenario of ALS.

ContextIntensity-modulated radiotherapy (IMRT) is a modern precision radiotherapy technique for the treatment of the pituitary adenoma.ObjectiveAim to investigate the efficacy and toxicity of IMRT in treating Cushing’s Disease (CD).Methods70 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.ResultsAt 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.ConclusionIMRT 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.

Abstract Background This research aimed to provide an overview of the impact of adjuvant vaginal brachytherapy (VBT) and external beam pelvic radiotherapy (EBRT) with or without VBT on survival in stage I to II EC patients in China from a long-term multi-institutional analysis. Methods We retrospectively analyzed stage I to II EC patients from 13 institutions treated between 2003 and 2015. All patients underwent surgical staging and received adjuvant RT. Patients were divided into groups of low-risk (LR), intermediate-risk (IR), high-intermediate-risk (HIR) and high-risk (HR). Survival statistics, failure pattern, and toxicity of different radiation modalities in different risk groups were analyzed. Results A total of 1048 patients were included. HR disease represented 27.6%, HIR 17.7%, IR 27.7% and LR 27.1%, respectively. Endometrioid adenocarcinoma (EAC) and non-endometrioid carcinoma (NEC) accounted for 92.8 and 7.2%. A total of 474 patients received VBT alone and 574 patients received EBRT with or without VBT. As for EAC patients, the 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rate was: 94.6, 90.4, 93.0 and 91.6%, respectively. For LR patients, EBRT (with or without VBT) seemed to be a risk factor. With the higher risk category, the survival benefit of EBRT gradually became remarkable. EBRT (with or without VBT) significantly increased DFS, LRFS and DMFS compared to VBT alone in the HR group (p

Abstract Objective The study aimed to evaluate site‐specific recurrent patterns via competing risks analysis and hazard function to provide evidence for adjuvant treatment and follow‐up for early staged endometrial cancer (EC). Methods A total of 858 patients with International Federation of Gynecology and Obstetrics stage I–II EC who received adjuvant radiotherapy at our institution (2000–2017) were included. The radiotherapy modality comprised external beam radiotherapy (EBRT) with or without vaginal brachytherapy (VBT) or VBT alone. Competing risks analysis and hazard rate function were employed to evaluate the recurrence rate according to the ESMO–ESGO–ESTRO risk classification. Results The 5‐year overall survival rates of the low‐risk (LR), intermediate‐risk (IR), high–intermediate risk (HIR), and high‐risk (HR) groups were 96.1%, 95%, 93%, and 89.7%, respectively (p = 0.018). Sixty‐eight patients developed recurrence. The 5‐year incidence of distant recurrence was the highest in the HR group (14.87%), followed by the HIR (7.71%), IR (5.27%), and LR (1.26%) groups (Gray's test, p

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.

Abstract Background Although middle-aged and elderly users are the main group targeted by health maintenance-oriented WeChat official accounts (HM-WOAs), few studies have explored the relationship of these accounts and their users. Exploring the factors that influence the continuous adoption of WOAs is helpful to strengthen the health education of middle-aged and elderly individuals. Objective We developed a new theoretical model and explored the factors that influence middle-aged and elderly individuals' continuous usage intention for HM-WOA. Performance expectancy mediated the effects of the model in explaining continuous usage intention and introduced health literacy into the model. Methods We established a hybrid theoretical model on the basis of the unified theory of acceptance and use of technology 2 model (UTAUT2), the health belief model (BHM), protection motivation theory (PMT), and health literacy. We collected valid responses from 396 middle-aged and elderly users aged ≥ 45 years in China. To verify our hypotheses, we analyzed the data using structural equation modeling. Results Performance expectancy (β = 0.383, P

Abstract Background For stage I to II high-risk endometrioid adenocarcinoma patients, the optimal adjuvant radiotherapy modality remains controversial. The present study sought to optimize the treatment of pelvic external beam radiation (EBRT) with/or vaginal brachytherapy (VBT) for high-risk endometrioid adenocarcinoma patients in multiple radiation oncology centers across China. Methods This article retrospectively reviewed stage I to II patients with resected endometrioid adenocarcinoma treated at 13 radiation centers from 1999 to 2015. Patients were eligible if they had high-risk features (stage IB Grade 3 disease or stage II Grade 1–3 disease) on the basis of ESMO-ESGO-ESTRO risk group consensus. Results A total of 218 patients were included. Fifty-one patients received EBRT, 25 patients received VBT, and 142 patients were administered EBRT combined with VBT. The three groups were comparable in baseline characteristics, except the proportion of stage IB and Grade 3 disease in the VBT group was significantly higher and their age was older. Survival analysis showed that OS, DFS, LRFS and DMFS were significantly different among the three groups. Two out of three groups were compared with each other, and results demonstrated that DFS, LRFS and DMFS were worse in the VBT group than in the EBRT or EBRT + VBT group. The 3-year OS rates were 95.2, 85.2 and 95.1% in the EBRT, VBT and EBRT + VBT groups, respectively (p = 0.043). There was no significant difference in survival outcomes between EBRT group and EBRT + VBT group. A propensity matching analysis was performed to eliminate group differences. The results demonstrated that DFS and LRFS were significantly improved in the pelvic radiation group compared to the VBT group. Distant failure accounted for most of the failure patterns. Patients in the VBT group had significantly increased local and regional recurrence rates than patients in the EBRT or EBRT + VBT group. Acute and chronic radiation-induced toxicities were well tolerated for all patients. Conclusion For patients with postoperative stage I to II high-risk endometrioid adenocarcinoma, compared with VBT alone, radiotherapy modalities including EBRT significantly improved DFS, LRFS and DMFS with tolerable adverse effects. Overall survival was not significantly different between EBRT and EBRT + VBT modalities.

Abstract Purpose To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. Methods Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). Results Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32–0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45–0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. Conclusion Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

BackgroundRepeat expansions, including those in C9orf72 and ATXN2, have been implicated in amyotrophic lateral sclerosis (ALS). However, there have been few studies on the association of AR and NOP56 repeat expansion with ALS, especially in China. Accordingly, we aimed to evaluate the frequency of C9orf72 and ATXN2 repeat mutations and investigate whether NOP56 and AR repeat expansion are risk factors for ALS.MethodsIn this study, 736 ALS patients and several hundred healthy controls were recruited. Polymerase chain reaction (PCR) and repeat-primed PCR (RP-PCR) were performed to determine the repeat lengths in C9orf72, ATXN2, AR, and NOP56.ResultsGGGGCC repeats in C9orf72 were observed in six ALS patients (0.8%, 6/736) but not in any of the controls (0/365). The patients with pathogenic GGGGCC repeats showed shorter median survival times than those with a normal genotype (p = 0.006). Regarding ATXN2 CAG repeats, we identified that intermediate repeat lengths (29–34 copies) were associated with ALS (p = 0.033), and there was no difference in clinical characteristics between the groups with and without intermediate repeats (p > 0.05). Meanwhile, we observed that there was no association between the repeat size in AR and NOP56 and ALS (p > 0.05).ConclusionsOur results demonstrated that pathogenetic repeats in C9orf72 are rare in China, while intermediate CAG repeats in ATXN2 are more frequent but have no effect on disease phenotypes; the repeat size in AR and NOP56 may not be a risk factor for ALS.

BackgroundMental health is a public health problem of great concern. Previous studies show that textual features and individual psychological characteristics can influence the effect of receiving information.PurposeThis study explores whether textual features influence the persuasiveness of teenager students’ mental health education while considering the influence of risk preference.MethodsFrom November to December 2021, a cross-sectional study was conducted among 1,869 teenager students in grade 7–12 in Chongqing, China. Wilcoxon signed-rank test, multiple logistic regression, and subgroup analysis were used to analyze the data.ResultsAmong the four textual features mentioned in this study, a significant difference was reported in the persuasive effects of information with and without numerical features (p 0.05). Combined with those from the risk preference analysis, results showed that the regulatory effect of risk preference was only reflected in emotional conflicts. Students who prefer having no emotional conflict in the text showed the characteristics of risk avoidance, or lower grades, or rural or school accommodation. Most teenager students are also risk averse, especially females (or = 2.223, 95%CI:1.755–2.815) and juniors (or = 1.533, 95%CI: 1.198–1.963).ConclusionThe numbers, symbols, and positive emotions in the text generate an active effect on teenager students receiving mental health education. Students avoiding risk are inclined to read texts without emotional conflicts. The probability of male choosing texts with positive emotional polarity is 33.5% lower than that of female. Female students and those from lower grades also demonstrate a higher inclination to risk avoidance compared with their male and higher grade counterparts. Therefore, educational materials with different text characteristics should be developed for teenager students with varying characteristics.

A parameterized controller design approach is proposed to solve the problem of multi-objective control for vehicle active suspension systems by using symbolic computation. The considered model is a quarter-vehicle model of the active suspension system. The multi-objective robust control performances include the sprung mass acceleration, suspension deflection, and tire deflection. Based on dissipative Hamiltonian systems and Lyapunov function, a multi-objective $H_{\infty }$ controller design approach is developed, which can avoid solving Hamilton-Jacobi-Issacs equations. Then, an algorithm of solving semi-positive definite polynomial with tuning parameters is proposed by using symbolic computation. Furthermore, a method of parameter optimization is proposed. Simulations and comparation show that the control performance is significantly improved comparing with passive controlled systems and existing other control systems for active suspension systems.

Extensive studies have been conducted on the Dijkstra algorithm owing to its bright prospect. However, few of them have studied the surface path planning of mobile robots. Currently, some application fields (e.g., wild ground, planet ground, and game scene) need to solve the optimal surface path. This paper proposes an extended Dijkstra algorithm. We utilize the Delaunay triangulation to model the surface environment. Based on keeping the triangle side length unchanged, the triangle mesh on the surface is equivalently converted into a triangle on the two-dimensional plane. Through this transformation, we set up the two-dimensional developable passable channel of the surface and solve the optimal route on this channel. Traversing all the two-dimensional developable and passable paths of the surface, we can get the shortest route among all the optimal paths. Then the inverse transformation from the two-dimensional plane coordinates to the corresponding surface coordinates obtains the surface optimal path. The simulation results show that, compared with the traditional Dijkstra algorithm, this method improves the accuracy of the surface optimization path in single-robot single-target and multi-robot multi-target path planning tasks.

The abnormal activation of the NLRP3 inflammasome is closely related to the occurrence and development of many inflammatory diseases. Targeting the NLRP3 inflammasome has been considered an efficient therapy to treat infections. We found that dihydrotanshinone I (DHT) specifically blocked the canonical and non-canonical activation of the NLRP3 inflammasome. Nevertheless, DHT had no relation with the activation of AIM2 or the NLRC4 inflammasome. Further study demonstrated that DHT had no influences on potassium efflux, calcium flux, or the production of mitochondrial ROS. We also discovered that DHT suppressed ASC oligomerization induced by NLRP3 agonists, suggesting that DHT inhibited the assembly of the NLRP3 inflammasome. Importantly, DHT possessed a significant therapeutic effect on NLRP3 inflammasome–mediated sepsis in mice. Therefore, our results aimed to clarify DHT as a specific small-molecule inhibitor for the NLRP3 inflammasome and suggested that DHT can be used as a potential drug against NLRP3-mediated diseases.

ObjectiveThe role of salvage radiotherapy (RT) in the treatment for vaginal recurrence of cervical cancer in patients after prior surgery remains controversial. The aim of this study was to evaluate the efficacy and toxicity of salvage RT and explore prognostic factors associated with the survival after recurrence.MethodsPatients with cervical cancer, treated for vaginal recurrences at Peking Union Medical College Hospital between July 2011 and November 2019, were identified. All the patients underwent prior surgery for primary tumor and received salvage RT including external beam radiotherapy (EBRT), brachytherapy (BT), or both. The irradiation field and dose depended on the conditions of patients. Recurrence patterns were classified into four categories according to the site of recurrence. Prognostic factors on the overall survival (OS), progression-free survival (PFS), and local control (LC) were analyzed, and late toxicity was evaluated.ResultsA total of 141 patients were included in the analysis, with a median follow-up time of 40.8 months. The estimated 5-year OS, PFS, and LC rates were 81%, 75%, and 87%, respectively. In multivariate analysis, endovaginal recurrence and no irradiation history were favorable prognostic factors associated with OS (all p < 0.05), PFS (all p < 0.05), and LC (all p < 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) of the recurrence pattern is larger than the stage of primary tumor (0.734 vs. 0.670).ConclusionsRT was an effective treatment with tolerable toxicity for vaginal recurrences of cervical cancer in patients with prior surgery. Recurrence pattern and irradiation history were important prognostic factors.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor prognosis. In resectable PDAC, the recurrence rate is still high even when surgery and adjuvant chemotherapy (CT) are applied. Regional lymph node metastasis and positive margins are associated with higher recurrence risk and worse survival. Adjuvant radiotherapy has been explored, but its efficacy remains controversial. In recent years, some characteristics have been reported to stratify patients who may benefit from adjuvant chemoradiation (CRT), such as lymph node metastasis and margin status. Adjuvant chemotherapy followed by chemoradiation (CT-CRT) was also proposed. A total of 266 patients with resectable PDAC who have lymph node metastasis or R1 resection after surgery were enrolled. In multivariate Cox regression analyses, pancreatic body or tail tumor location (HR 0.433, p

Background: The myopia is a public health issue that attracts much attention. However, limited attention has been paid to the effect of primary school students' acceptance of health messages. Previous studies have found that framing effects and evidence types influence the persuasive effect of messages.Purpose: This study explored whether framing effects and evidence type influence the persuasive effect of myopia prevention messages among elementary school students and the influence of children's myopia prevention cognition was considered.Methods: A cross-sectional study was conducted among 1,493 elementary school students aged 9 to 13 in China from May to July 2020 by convenience sampling. Wilcoxon signed-rank test and multinomial logistic regression were used for data analysis.Results: Significant differences were found in the persuasive effect between statistical and non-statistical evidence messages (p < 0.001). Among non-statistical evidence messages, gain-framed messages showed a greater persuasive effect than loss-framed messages (p < 0.001). Among statistical evidence messages, loss-framed messages performed better than gain-framed messages (p < 0.001). Children's myopia prevention cognition exerted no significant effect on the persuasive effect of the messages (p > 0.05).Conclusion: This study demonstrated the influence of framing effect on the persuasive effect of myopia prevention messages among children aged 9 to 13 in China. Non-statistical evidence messages showed a better persuasive effect than statistical evidence messages. Different types of evidence influenced the persuasive effect of gain- and loss- framed messages. These findings have implications for strategies more or less likely to work in making myopia prevention messages for children.

Abstract Background The new staging system of cervical cancer issued in 2018 by the International Federation of Gynecology and Obstetrics (FIGO), calls for a new evaluation of the efficacy of prophylactic extended field irradiation (EFI) in the concomitant chemoradiotherapy/brachytherapy treatment of locally advanced cervical cancer patients (stage IIIB). Methods We performed a retrospective study consisting of 133 FIGO IIIB cervical cancer patients treated in the Peking Union Medical College Hospital from 2002 to 2010. The patients were distributed in two groups depending whether they were treated with EFI or pelvic only irradiation. The therapeutic efficacy, toxicity and prognostic factors of EFI were evaluated in the frame of the new FIGO staging system. Results When compared to patients who received pelvic only irradiation, patients who received prophylactic EFI showed significantly less distant metastasis and a significant improvement in their 5 years overall survival (OS), disease free survival (DFS), out of field recurrence free survival (OFRFS) and para-aortic lymph node metastasis free survival (PALNMFS). Multivariate analysis revealed that EFI is an independent prognosis factor for DFS, OFRFS and PALNMFS. Finally, although more acute complications were observed in the EFI group, there is no significantly worst acute toxicity in the EFI group. Conclusion Our retrospective analysis supports the prophylactic effect of EFI in the concomitant chemoradiotherapy treatment of IIIB patients and suggests that this prophylactic effect is associated with a clear improvement in 5-years OS, DFS, OFRFS and PALNMFS. Consequently, EFI appears to be a very valid treatment option for FIGO IIIB cervical cancer patients.

Abstract Background To compare irradiation dose to the second and third portions of duodenum (Duo2 and Duo3) with a new refined and old delineation method of para-aortic region for patients with locally advanced cervical cancer (LACC) receiving prophylactic extended-field radiotherapy (EFRT). Methods Twenty consecutive patients with LACC were treated with prophylactic EFRT from January 2016 to January 2017 at our institute. Two delineation methods of para-aortic region were designed for each patient, the old delineation method ensured a full coverage of aortic and inferior vena cava, while the right paracaval region above L3 was omitted from CTV in the new delineation method. Patients received a dose of 50.4Gy in 28 fractions for PCTV and a dose of 60.2Gy in 28 fractions for PGTV with volumetric-modulated arc therapy (VMRT). The dose delivered to Duo2 and Duo3 with these two delineation methods were compared. Results All treatment plans achieved excellent target volume coverage with 95% of PCTV receiving 50.4Gy and 95% of PGTV receiving 60.2Gy. There was no difference between delineation methods in low dose level (V5, V10, V15, V20, V25) for Duo2 and Duo3. The V30, V35, V40, V45, V50, Dmax, Dmean and D2cc for Duo2 with the new and old delineation methods were 55.76% vs 80.54% (P = 0.009), 34.72% vs 70.91% (P

In this paper, a general parametric controller design method is presented for two-dimensional (2D) linear discrete systems described by the Fornasini-Marchesini second model. This method is based on the discriminant systems of polynomial and Hurwitz theorem. By the fractional linear transformation, the problem of stability analysis for 2D systems can be turned to a new problem whether the polynomials are Hurwitz stable. Thus, the process of stability analysis is changed into a problem whether some polynomials are positive definite, which can be easily checked by the discriminant system of the polynomial. It simplifies some existing methods of analyzing stability for 2D systems. Then, we apply the process proposed stability analysis method to consider the stabilization problem. A parametric controller is derived. The form of the parametric controller designed by the proposed method is simple, the parameters of the controller law can be fully solved. Finally, we give two numerical examples and a practical example of a chemical reactor thermal process to show the validity of the proposed methods.

In this paper, we propose a method to test the stability of two-dimensional (2D) linear discrete systems described by transfer function. And a complete region of disturbance parameters is solved to ensure the considered system with perturbations stability. Different from any other traditional algebraic methods, the algorithm of this method is explicit, which a large number of higher-order polynomial iterative operation doesn't need to be carried out. By the fractional linear transformations, new condition is given in Hurwitz theorem, which doesn't involve fractional calculation. The method is non-conservative for stability analysis and solving stable parameter region of 2D systems. It simplifies some existing methods. The computational cost is reduced. And it is better to solve the stability problems for 2D systems with disturbances. Examples illustrate the efficiency for testing the stability of higher-order 2D system and solving the robust stability problem of uncertain 2D systems.

With the wide application of Bioinspired Neural Network in the field of robot path planning, the environmental scale of robot path planning is getting larger, and the environmental resolution requirements are getting higher. However, with the increase of the environment size and resolution requirement, the neuronal activity value calculation cost and the time cost of the Bioinspired Neural Network will increase sharply. Aiming at this problem, this paper proposes an improved Bioinspired Neural Network path planning method based on Scaling Terrain. Using a Multi-Scale Map method and Dijkstra algorithm, the optimal path of a Coarse Scale Map is calculated. The optimal path obtained from the Coarse Scale Map is used to guide the neural network planning weights of the Fine Scale Map from the same terrain. Thus, the optimal path of the Fine Scale Map can be calculated by the improved BNN algorithm. Introducing this Multi-Scale Map Method into the Bioinspired Neural Network can greatly reduce the time cost of the Bioinspired Neural Network path planning algorithm and reduce the mathematical complexity. Simulation results in some computer integrated virtual environments further demonstrate the superiority of this method and the experimental results are encouraging.

Based on the generalized Routh–Hurwitz criterion, we propose a sufficient and necessary criterion for testing the stability of fractional-order linear systems with order α∈1,2, called the fractional-order Routh–Hurwitz criterion. Compared with the existing criterion, ours involves fewer and simpler expressions, which is significant for analyzing the robust stability of high-dimensional uncertain systems. All these expressions are explicit ones about the coefficients of the characteristic polynomial of the system matrix, so the stable parameter region of fractional-order systems can be described directly. Some examples show the effectiveness of our method.

This paper proposes a new fractional-order model reference adaptive control (FOMRAC) framework for a fractional-order multivariable system with parameter uncertainty. The designed FOMRAC scheme depends on a fractional-order nonlinear scalar update law. Specifically, the scalar update law does not change as the input–output dimension changes. The main advantage of the proposed adaptive controller is that only one parameter online update is needed such that the computational burden in the existing FOMRAC can be relieved. Furthermore, we show that all signals in this adaptive scheme are bounded and the mean value of the squared norm of the error converges to zero. Two illustrative numerical examples are presented to demonstrate the efficiency of the proposed control scheme.

This paper puts forward a novel output feedback model reference adaptive control (MRAC) scheme for solving an adaptive output tracking problem. The proposed control scheme only needs a scalar function to be updated online, which decreases the system adaptation complexity, compared to the existing MRAC schemes. Furthermore, the closed-loop signal boundedness and asymptotic output tracking are guaranteed with the proposed MRAC scheme. A simulation study is carried out to verify the effectiveness of the established approach.

Objective: The study aims to investigate public awareness of coronavirus disease 2019 (COVID-19) and measure levels of anxiety during the outbreak. Method: A total of 2115 subjects from 34 provinces in China were evaluated. A questionnaire was designed, which covers demographic characteristics, knowledge of COVID-19, and factors that influenced anxiety during the outbreak to test public awareness and determine the impact of the outbreak on people's lives. In addition, a generalized anxiety disorder (GAD) scale was utilized to assess anxiety levels during the outbreak. Lastly, the chi-square test and multiple logistic regression analysis were used to identify factors associated with levels of public anxiety. Results: A majority of respondents reported high levels of awareness of COVID-19. A total of 1107 (52.3%), 707 (33.4%), 154 (7.3%), and 147 (7%) respondents exhibited no, mild, moderate, and severe levels of anxiety, respectively. Results of the chi-square test and multiple logistic regression analysis demonstrated that respondents (a) with no college education, (b) are unaware of neighbors who may have been infected, (c) who spent considerable time collecting information and browsing negative information related to the virus, (d) are unhealthy, and (e) displayed low levels of awareness of the transmission routes were highly likely to be anxious. Conclusion: During the outbreak, the majority of people exhibited high levels of awareness and knowledge regarding preventive measures from COVID-19. The absence of psychological anxiety was observed in more than half of the respondents. Adaptive responses to anxiety and high levels of awareness about COVID-19 may have protected the public during the outbreak.

BackgroundThis study aims to construct and validate a model based on convolutional neural networks (CNNs), which can fulfil the automatic segmentation of clinical target volumes (CTVs) of breast cancer for radiotherapy.MethodsIn this work, computed tomography (CT) scans of 110 patients who underwent modified radical mastectomies were collected. The CTV contours were confirmed by two experienced oncologists. A novel CNN was constructed to automatically delineate the CTV. Quantitative evaluation metrics were calculated, and a clinical evaluation was conducted to evaluate the performance of our model.ResultsThe mean Dice similarity coefficient (DSC) of the proposed model was 0.90, and the 95th percentile Hausdorff distance (95HD) was 5.65 mm. The evaluation results of the two clinicians showed that 99.3% of the chest wall CTV slices could be accepted by clinician A, and this number was 98.9% for clinician B. In addition, 9/10 of patients had all slices accepted by clinician A, while 7/10 could be accepted by clinician B. The score differences between the AI (artificial intelligence) group and the GT (ground truth) group showed no statistically significant difference for either clinician. However, the score differences in the AI group were significantly different between the two clinicians. The Kappa consistency index was 0.259. It took 3.45 s to delineate the chest wall CTV using the model.ConclusionOur model could automatically generate the CTVs for breast cancer. AI-generated structures of the proposed model showed a trend that was comparable, or was even better, than those of human-generated structures. Additional multicentre evaluations should be performed for adequate validation before the model can be completely applied in clinical practice.

Patients with advanced-stage natural killer/T-cell lymphoma (NKTCL) usually have a poor prognosis. However, there is limited data of comprehensive analysis on this particular patient population due to the rarity of the disease. The present study aimed to investigate the treatment models, survival outcomes, and prognosis of advanced-stage NKTCL. Data from 336 patients with advanced-stage NKTCL diagnosed between 2006 and 2015 in the China Lymphoma Collaborative Group database were retrospectively analyzed. The median age was 42 years and the male/female ratio was 2.4:1. About 97% of patients had stage IV disease and 77% had >1 extranodal involvement site. All patients received chemotherapy, with the most common option being asparaginase (Asp)-containing regimens (n=146; 43.5%). Among 286 patients with available response data, the overall response rate (ORR) was 57.3% with a complete remission (CR) rate of 35.7%. Asp-containing regimens led to better ORRs (86/132, 65.2% vs. 54/113, 47.8%, P = 0.006) and CR rates (60/132, 45.5% vs. 27/113, 23.9%, P < 0.001) than non-Asp-containing regimens. The expected 5-year progression-free survival (PFS) and overall survival (OS) rates were 22.6 and 32.0%, respectively, for the whole cohort. Compared to non-Asp-containing chemotherapy, Asp-containing chemotherapy improved 5-year PFS (34.2 vs. 17.1%, P < 0.001) and OS (45.3 vs. 27.8%, P < 0.001). A trend toward improvement in OS was observed when gemcitabine was added to Asp-containing chemotherapies. Moreover, those undergoing autologous hematopoietic stem cell transplantation had prolonged survival time. In conclusion, Asp-containing chemotherapy could improve the prognosis of advanced-stage NKTCL, and refinement of treatment models is warranted in the future.

ObjectiveLow-grade endometrial stromal sarcoma (LG-ESS) is a rare gynecological tumor. Whether adjuvant radiotherapy benefits survival in patients with resected early-stage ESS remains controversial. This study was designed to explore the role of adjuvant radiotherapy in stage I to II LG-ESS.MethodsWe retrospectively reviewed patients with stage I to II LG-ESS in our center from Jan. 1998 to Feb. 2018. All patients underwent a total hysterectomy and postoperative radiotherapy was administrated based on clinical and pathological characteristics.ResultsA total of 152 patients with stage I to II resected LG-ESS were included. Forty patients received adjuvant radiotherapy (RT group) while 112 patients did not receive adjuvant radiotherapy (no RT group). The baseline characteristics of the two groups were comparable, except that the proportion of stage II patients in the RT group was higher than that in the no RT group (32.5% vs. 11.6%, in RT vs. no RT groups, respectively; p = 0.003). For both patient groups, median overall survival was not reached. The median disease-free survival (DFS) was 144 months. Radiotherapy was associated with significantly improved DFS (92 months vs. not reached in RT vs. no RT groups, respectively; p = 0.008) and pelvic failure-free survival (PFFS) (92 months vs. not reached in RT vs. no RT groups, respectively; p=0.004). Subgroup analysis revealed that RT benefited survival most among patients with stage IB to IIB disease. Adjuvant radiotherapy significantly reduced the pelvic recurrence rate (10.0%, 4/40 vs. 28.6%, 32/112, p = 0.018). No radiotherapy-induced grade 4 to 5 toxicity was observed.ConclusionFor patients with stage I to II LG-ESS, adjuvant radiotherapy showed significant improvement in DFS and PFFS with tolerable adverse effects, especially in patients with stage IB to IIB disease.

This paper considers the stability and stabilization of two-dimensional (2D) fractional-order systems described by state-space model based on the discrimination system of polynomials. Necessary and sufficient conditions of stability and stabilization are established. We change the criterion for checking the stability of linear discrete-time 2D fractional-order systems into an easy checking criterion whether some polynomials are positive. We use the discrimination system of polynomials to check the new conditions. For the stabilization problem, we get a stable gain matrix region. The unstable system with the gain parameters of the stable gain matrix region is stable. We give the method of stability analysis and stabilization for the general 2D fractional-order system. An example shows the validity of the proposed stability and stabilization methods.

Variants in the DNAJC7 gene have been shown to be novel causes of amyotrophic lateral sclerosis (ALS). However, the contributions of DNAJC7 mutations in Asian ALS patients remain unclear. In this study, we screened rare pathogenic variants in the DNAJC7 gene in a cohort of 578 ALS patients from Mainland China. A novel, rare, putative pathogenic variant c.712A>G (p.R238G) was identified in one sporadic ALS patient. The carrier with this variant exhibited symptom onset at a relatively younger age and experienced rapid disease progression. Our results expand the pathogenic variant spectrum of DNAJC7 and indicate that variants in the DNAJC7 gene may also contribute to ALS in the Chinese population.